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Purpose: The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes., Methods and Materials: Forty-five radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the RCT protocol. The probability of biochemical failure (BF) was determined using a model from the RCT. The primary metric evaluated was delta BF (DBF = Participant BF - Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful., Results: Eight patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. Of participant plans, 37% were noted to have an absolute increase in BF of 5% or more., Conclusions: Radiation oncologists' attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The purpose of the present study is to develop a calibration method to account for differences in echo times (TE) and facilitate the use of restriction spectrum imaging restriction score (RSIrs) as a quantitative biomarker for the detection of clinically significant prostate cancer (csPCa)., Methods: This study included 197 consecutive patients who underwent MRI and biopsy examination; 97 were diagnosed with csPCa (grade group ≥ 2). RSI data were acquired three times during the same session: twice at minimum TE ~75 ms and once at TE = 90 ms (TEmin 1 , TEmin 2 , and TE90, respectively). A linear regression model was determined to match the C-maps of TE90 to the reference C-maps of TEmin 1 within the interval ranging from 95th to 99th percentile of signal intensity within the prostate. RSIrs comparisons were made at the 98th percentile within each patient's prostate. We compared RSIrs from calibrated TE90 (RSIrs TE90corr ) and uncorrected TE90 (RSIrs TE90 ) to RSIrs from reference TEmin 1 (RSIrs TEmin1 ) and repeated TEmin 2 (RSIrs TEmin2 ). Calibration performance was evaluated with sensitivity, specificity and area under the ROC curve (AUC)., Results: Scaling factors for C 1 , C 2 , C 3 , and C 4 were estimated as 1.68, 1.33, 1.02, and 1.13, respectively. In non-csPCa cases, the 98th percentile of RSIrs TEmin2 and RSIrs TEmin1 differed by 0.27 ± 0.86SI (mean ± standard deviation), whereas RSIrs TE90 differed from RSIrs TEmin1 by 1.82 ± 1.20SI. After calibration, this bias was reduced to -0.51 ± 1.21SI, representing a 72% reduction in absolute error. For patients with csPCa, the difference was 0.54 ± 1.98SI between RSIrs TEmin2 and RSIrs TEmin1 and 2.28 ± 2.06SI between RSIrs TE90 and RSIrs TEmin1 . After calibration, the mean difference decreased to -1.03SI, a 55% reduction in absolute error. At the Youden index for patient-level classification of csPCa (8.94SI), RSIrs TEmin1 has a sensitivity of 66% and a specificity of 72%., Conclusions: The proposed linear calibration method produces similar quantitative biomarker values for acquisitions with different TE, reducing TE-induced error by 72% and 55% for non-csPCa and csPCa, respectively., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Multi-segment foot models (MFMs) provide a better understanding of the intricate biomechanics of the foot, yet it is unclear if they accurately differentiate foot type function during locomotion., Research Question: We employed an MFM to detect subtle kinematic differences between foot types, including: pes cavus, neutrally aligned, and asymptomatic and symptomatic pes planus. The study investigates how variable the results of this MFM are and if it can detect kinematic differences between pathologic and non-pathologic foot types during the stance phase of gait., Methods: Independently, three raters instrumented three subjects on three days to assess variability. In a separate cohort, each foot type was statically quantified for ten subjects per group. Each subject walked while instrumented with a four-segment foot model to assess static alignment and foot motion during the stance phase of gait. Statistical analysis performed with a linear mixed effects regression., Results: Model variability was highest for between-day and lowest for between-rater, with all variability measures being within the true sample variance. Almost all static measures (radiographic, digital scan, and kinematic markers) differed significantly by foot type. Sagittal hindfoot to leg and forefoot to leg kinematics differed between foot types during late stance, as well as coronal hallux to forefoot range of motion. The MFM had low between-rater variability and may be suitable for multiple raters to apply to a single study sample without introducing significant error. The model, however, only detected a few dynamic differences, with the most dramatic being the hallux to forefoot coronal plane range of motion., Significance: Results only somewhat aligned with previous work. It remains unclear if the MFM is sensitive enough to accurately detect different motion between foot types (pathologic and non-pathologic). A more accurate method of tracking foot bone motion (e.g., biplane fluoroscopy) may be needed to address this question., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier B.V.)

Children in rural communities consume more energy-dense foods relative to their urban peers. Identifying effective interventions for improving energy intake patterns are needed to address these geographic disparities. The primary aim of this study was to harness the benefits of physical activity on children's executive functioning to see if these improvements lead to acute changes in eating behaviors. In a randomized crossover design, 91 preadolescent (8-10y; M age = 9.48 ± 0.85; 50.5% female; 85.7% White, 9.9% Multiracial, 9.9% Hispanic) children (86% rural) completed a 20-minute physical activity condition (moderate intensity walking) and time-matched sedentary condition (reading and/or coloring) ~ 14 days apart. Immediately following each condition, participants completed a behavioral inhibition task and then eating behaviors (total energy intake, relative energy intake, snack intake) were measured during a multi-array buffet test meal. After adjusting for period and order effects, body fat (measured via DXA), and depressive symptoms, participants experienced significant small improvements in their behavioral inhibition following the physical activity versus sedentary condition (p = 0.04, Hedge's g = 0.198). Eating behaviors did not vary by condition, nor did improvements in behavioral inhibition function as a mediator (ps > 0.09). Thus, in preadolescent children, small improvements in behavioral inhibition from physical activity do not produce acute improvements in energy intake. Additional research is needed to clarify whether the duration and/or intensity of physical activity sessions would produce different results in this age group, and whether intervention approaches and corresponding mechanisms of change vary by individual factors, like age and degree of food cue responsivity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Mongold, SJ, Ricci, AW, Hahn, ME, and Callahan, DM. Skeletal muscle compliance and echogenicity in resistance-trained and nontrained women. J Strength Cond Res 38(4): 671-680, 2024-Noninvasive assessment of muscle mechanical properties in clinical and performance settings tends to rely on manual palpation and emphasizes examination of musculotendinous stiffness. However, measurement standards are highly subjective. The purpose of the study was to compare musculotendinous stiffness in adult women with varying resistance training history while exploring the use of multiple tissue compliance measures. We identified relationships between tissue stiffness and morphology, and tested the hypothesis that combining objective measures of morphology and stiffness would better predict indices of contractile performance. Resistance-trained (RT) women (n = 11) and nontrained (NT) women (n = 10) participated in the study. Muscle echogenicity and morphology were measured using B-mode ultrasonography (US). Vastus lateralis (VL) and patellar tendon (PT) stiffness were measured using digital palpation and US across submaximal isometric contractions. Muscle function was evaluated during maximal voluntary isometric contraction (MVIC) of the knee extensors (KEs). Resistance trained had significantly greater PT stiffness and reduced echogenicity (p < 0.01). Resistance trained also had greater strength per body mass (p < 0.05). Muscle echogenicity was strongly associated with strength and rate of torque development (RTD). Patellar tendon passive stiffness was associated with RTD normalized to MVIC (RTDrel; r = 0.44, p < 0.05). Patellar tendon stiffness was greater in RT young women. No predictive models of muscle function incorporated both stiffness and echogenicity. Because RTDrel is a clinically relevant measure of rehabilitation in athletes and can be predicted by digital palpation, this might represent a practical and objective measure in settings where RTD may not be easy to measure directly., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the National Strength and Conditioning Association.)

Objective: To identify vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery., Design: Secondary analysis of magnetic resonance images (MRI) of the Defining Mechanisms of Anterior Vaginal Wall Descent cross-sectional study., Setting: Eight clinical sites in the US Pelvic Floor Disorders Network., Population or Sample: Women who underwent vaginal mesh hysteropexy (hysteropexy) with sacrospinous fixation or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) for uterovaginal prolapse between April 2013 and February 2015., Methods: The MRI (rest, strain) obtained 30-42 months after surgery, or earlier for participants with recurrence who desired reoperation before 30 months, were analysed. MRI-based prolapse recurrence was defined as prolapse beyond the hymen at strain on MRI. Vaginal segmentations (at rest) were used to create three-dimensional models placed in a morphometry algorithm to quantify and compare vaginal morphology (angulation, dimensions) and position., Main Outcome Measures: Vaginal angulation (upper, lower and upper-lower vaginal angles in the sagittal and coronal plane), dimensions (length, maximum transverse width, surface area, volume) and position (apex, mid-vagina) at rest., Results: Of the 82 women analysed, 12/41 (29%) in the hysteropexy group and 22/41 (54%) in the hysterectomy group had prolapse recurrence. After hysteropexy, women with recurrence had a more laterally deviated upper vagina (p = 0.02) at rest than women with successful surgery. After hysterectomy, women with recurrence had a more inferiorly (lower) positioned vaginal apex (p = 0.01) and mid-vagina (p = 0.01) at rest than women with successful surgery., Conclusions: Vaginal angulation and position were associated with prolapse recurrence and suggestive of vaginal support mechanisms related to surgical technique and potential unaddressed anatomical defects. Future prospective studies in women before and after prolapse surgery may distinguish these two factors., (© 2023 John Wiley & Sons Ltd.)

Postural control is one of the primary body functions for fall prevention. Unexpected perturbation-based balance training is effective for improving postural control. However, the effect of perturbation-based training using assistive devices on muscle activity and co-contraction for standing balance is still unclear. This training is also difficult to perform easily because it requires large instruments or expert guidance. The purpose of this study is to demonstrate the effect of perturbation-based balance training using a wearable balance training device (WBTD) on postural control. In this study, fourteen healthy young adult males were assigned to either a WBTD group or a sham group. In the intervention session, participants in the WBTD group were perturbed either left or right direction at random timing by the WBTD during tandem stance balance training. Participants in the Sham group did not receive external perturbation during tandem stance balance training. Before and after the intervention session, participants of both groups underwent unexpected lateral perturbation postural control testing (pre- and post-test). The normalized integral of electromyography (IEMG), co-contraction index (CCI), and center of pressure (COP) parameters were measured in the pre- and post-test. Experimental results showed that the WBTD group in the post-test significantly decreased left Gluteus Medius IEMG, CCI of both Gluteus Medius, and peak [Formula: see text] velocity, compared to those of the pre-test ( [Formula: see text], p =0.024 , p =0.031 , respectively). We conclude that balance training using WBTD could improve flexible postural control adjustment via cooperative muscle activation.

Purpose: In a phase III randomized trial, adding a radiation boost to tumor(s) visible on MRI improved prostate cancer (PCa) disease-free and metastasis-free survival without additional toxicity. Radiation oncologists' ability to identify prostate tumors is critical to widely adopting intraprostatic tumor radiotherapy boost for patients. A diffusion MRI biomarker, called the Restriction Spectrum Imaging restriction score (RSIrs), has been shown to improve radiologists' identification of clinically significant PCa. We hypothesized that (1) radiation oncologists would find accurately delineating PCa tumors on conventional MRI challenging and (2) using RSIrs maps would improve radiation oncologists' accuracy for PCa tumor delineation., Methods and Materials: In this multi-institutional, international, prospective study, 44 radiation oncologists (participants) and 2 expert radiologists (experts) contoured prostate tumors on 39 total patient cases using conventional MRI with or without RSIrs maps. Participant volumes were compared to the consensus expert volumes. Contouring accuracy metrics included percent overlap with expert volume, Dice coefficient, conformal number, and maximum distance beyond expert volume., Results: 1604 participant volumes were produced. 40 of 44 participants (91%) completely missed ≥1 expert-defined target lesion without RSIrs, compared to 13 of 44 (30%) with RSIrs maps. On conventional MRI alone, 134 of 762 contour attempts (18%) completely missed the target, compared to 18 of 842 (2%) with RSIrs maps. Use of RSIrs maps improved all contour accuracy metrics by approximately 50% or more. Mixed effects modeling confirmed that RSIrs maps were the main variable driving improvement in all metrics. System Usability Scores indicated RSIrs maps significantly improved the contouring experience (72 vs. 58, p < 0.001)., Conclusions: Radiation oncologists struggle with accurately delineating visible PCa tumors on conventional MRI. RSIrs maps improve radiation oncologists' ability to target MRI-visible tumors for prostate tumor boost., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Demonstration of a very dense or hyper-attenuated liver on the pre-contrast CT images of the abdomen can be an unexpected finding. It may present as a diagnostic challenge if the underlying cause of it is not apparent from the provided clinical history. There are about 12 different pathologic conditions that are associated with deposition of radiopaque elements within the hepatic parenchyma, resulting in diffuse or multi-lobar hyperdense appearance of the liver on abdominal radiographs and CT. Most of them are drug-induced or iatrogenic in nature, while others are the sequelae of genetic disorders like thalassemia, Wilson's disease, and primary hemochromatosis. This pictorial essay will present the CT appearance and etiology of hyper-attenuated liver in various clinical entities., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest, The authors declare that they have no disclosure relevant to the subject matter of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In laboratory experiments, biomechanical data collections with wearable technologies and machine learning have been promising. Despite the development of lightweight portable sensors and algorithms for the identification of gait events and estimation of kinetic waveforms, machine learning models have yet to be used to full potential. We propose the use of a Long Short Term Memory network to map inertial data to ground reaction force data gathered in a semi-uncontrolled environment. Fifteen healthy runners were recruited for this study, with varied running experience: novice to highly trained runners (<15 min 5 km race), and ages ranging from 18 to 64 years old. Force sensing insoles were used to measure normal foot-shoe forces, providing the standard for identification of gait events and measurement of kinetic waveforms. Three inertial measurement units (IMUs) were mounted to each participant, two bilaterally on the dorsal aspect of the foot and one clipped to the back of each participant's waistband, approximating their sacrum. Data input into the Long Short Term Memory network were from the three IMUs and output were estimated kinetic waveforms, compared against the standard of the force sensing insoles. The range of RMSE for each stance phase was from 0.189-0.288 BW, which is similar to multiple previous studies. Estimation of foot contact had an r 2  = 0.795. Estimation of kinetic variables varied, with peak force presenting the best output with an r 2  = 0.614. In conclusion, we have shown that at controlled paces over level ground a Long Short Term Memory network can estimate 4 s temporal windows of ground reaction force data across a range of running speeds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Donahue and Hahn.)

Wearable sensors and machine learning algorithms are becoming a viable alternative for biomechanical analysis outside of the laboratory. The purpose of this work was to estimate gait events from inertial measurement units (IMUs) and utilize machine learning for the estimation of ground reaction force (GRF) waveforms. Sixteen healthy runners were recruited for this study, with varied running experience. Force sensing insoles were used to measure normal foot-shoe forces, providing a proxy for vertical GRF and a standard for the identification of gait events. Three IMUs were mounted on each participant, two bilaterally on the dorsal aspect of each foot and one clipped to the back of each participant's waistband, approximating their sacrum. Participants also wore a GPS watch to record elevation and velocity. A Bidirectional Long Short Term Memory Network (BD-LSTM) was used to estimate GRF waveforms from inertial waveforms. Gait event estimation from both IMU data and machine learning algorithms led to accurate estimations of contact time. The GRF magnitudes were generally underestimated by the machine learning algorithm when presented with data from a novel participant, especially at faster running speeds. This work demonstrated that estimation of GRF waveforms is feasible across a range of running velocities and at different grades in an uncontrolled environment., (© 2023. The Author(s).)

Purpose To develop a multicompartmental signal model for whole-body diffusion-weighted imaging (DWI) and apply it to study the diffusion properties of normal tissue and metastatic prostate cancer bone lesions in vivo. Materials and Methods This prospective study ( ClinicalTrials.gov : NCT03440554) included 139 men with prostate cancer (mean age, 70 years ± 9 [SD]). Multicompartmental models with two to four tissue compartments were fit to DWI data from whole-body scans to determine optimal compartmental diffusion coefficients. Bayesian information criterion (BIC) and model-fitting residuals were calculated to quantify model complexity and goodness of fit. Diffusion coefficients for the optimal model (having lowest BIC) were used to compute compartmental signal-contribution maps. The signal intensity ratio (SIR) of bone lesions to normal-appearing bone was measured on these signal-contribution maps and on conventional DWI scans and compared using paired t tests (α = .05). Two-sample t tests (α = .05) were used to compare compartmental signal fractions between lesions and normal-appearing bone. Results Lowest BIC was observed from the four-compartment model, with optimal compartmental diffusion coefficients of 0, 1.1 × 10 -3 , 2.8 × 10 -3 , and >3.0 ×10 -2 mm 2 /sec. Fitting residuals from this model were significantly lower than from conventional apparent diffusion coefficient mapping ( P < .001). Bone lesion SIR was significantly higher on signal-contribution maps of model compartments 1 and 2 than on conventional DWI scans ( P < .008). The fraction of signal from compartments 2, 3, and 4 was also significantly different between metastatic bone lesions and normal-appearing bone tissue ( P ≤ .02). Conclusion The four-compartment model best described whole-body diffusion properties. Compartmental signal contributions from this model can be used to examine prostate cancer bone involvement. Keywords: Whole-Body MRI, Diffusion-weighted Imaging, Restriction Spectrum Imaging, Diffusion Signal Model, Bone Metastases, Prostate Cancer Clinical trial registration no. NCT03440554 Supplemental material is available for this article. © RSNA, 2023 See also commentary by Margolis in this issue.

Background: Multiparametric magnetic resonance imaging (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the subjective Prostate Imaging Reporting and Data System (PI-RADS) system and quantitative apparent diffusion coefficient (ADC) are inconsistent. Restriction spectrum imaging (RSI) is an advanced diffusion-weighted MRI technique that yields a quantitative imaging biomarker for csPCa called the RSI restriction score (RSI rs )., Objective: To evaluate RSI rs for automated patient-level detection of csPCa., Design Setting and Participants: We retrospectively studied all patients ( n  = 151) who underwent 3 T mpMRI and RSI (a 2-min sequence on a clinical scanner) for suspected prostate cancer at University of California San Diego during 2017-2019 and had prostate biopsy within 180 d of MRI., Intervention: We calculated the maximum RSI rs and minimum ADC within the prostate, and obtained PI-RADS v2.1 from medical records., Outcome Measurements and Statistical Analysis: We compared the performance of RSI rs , ADC, and PI-RADS for the detection of csPCa (grade group ≥2) on the best available histopathology (biopsy or prostatectomy) using the area under the curve (AUC) with two-tailed α  = 0.05. We also explored whether the combination of PI-RADS and RSI rs might be superior to PI-RADS alone and performed subset analyses within the peripheral and transition zones., Results and Limitations: AUC values for ADC, RSI rs , and PI-RADS were 0.48 (95% confidence interval: 0.39, 0.58), 0.78 (0.70, 0.85), and 0.77 (0.70, 0.84), respectively. RSI rs and PI-RADS were each superior to ADC for patient-level detection of csPCa ( p  < 0.0001). RSI rs alone was comparable with PI-RADS ( p  = 0.8). The combination of PI-RADS and RSI rs had an AUC of 0.85 (0.78, 0.91) and was superior to either PI-RADS or RSI rs alone ( p  < 0.05). Similar patterns were seen in the peripheral and transition zones., Conclusions: RSI rs is a promising quantitative marker for patient-level csPCa detection, warranting a prospective study., Patient Summary: We evaluated a rapid, advanced prostate magnetic resonance imaging technique called restriction spectrum imaging to see whether it could give an automated score that predicted the presence of clinically significant prostate cancer. The automated score worked about as well as expert radiologists' interpretation. The combination of the radiologists' scores and automated score might be better than either alone., (© 2022 The Authors.)

Zero-velocity assumption has been used for estimation of foot trajectory and stride length during running from the data of foot-mounted inertial measurement units (IMUs). Although the assumption provides a reasonable initialization for foot trajectory and stride length estimation, the other source of errors related to the IMU's orientation still remains. The purpose of this study was to develop an improved foot trajectory and stride length estimation method for the level ground running based on the displacement of the foot. Seventy-nine runners performed running trials at 5 different paces and their running motions were captured using a motion capture system. The accelerations and angular velocities of left and right feet were measured with two IMUs mounted on the dorsum of each foot. In this study, foot trajectory and stride length were estimated using zero-velocity assumption with IMU data, and the orientation of IMU was estimated to calculate the mediolateral and vertical distance of the foot between two consecutive midstance events. Calculated foot trajectory and stride length were compared with motion capture data. The results show that the method used in this study can provide accurate estimation of foot trajectory and stride length for level ground running across a range of running speeds.

Introduction: Loading of a residual limb within a prosthetic socket can cause tissue damage such as ulceration. Computational simulations may be useful tools for estimating tissue loading within the socket, and thus provide insights into how prosthesis designs affect residual limb-socket interface dynamics. The purpose of this study was to model and simulate residual limb-socket interface dynamics and evaluate the effects of varied prosthesis stiffness on interface dynamics during gait. Methods: A spatial contact model of a residual limb-socket interface was developed and integrated into a gait model with a below-knee amputation. Gait trials were simulated for four subjects walking with low, medium, and high prosthesis stiffness settings. The effects of prosthesis stiffness on interface kinematics, normal pressure, and shear stresses were evaluated. Results: Model-predicted values were similar to those reported previously in sensor-based experiments; increased stiffness resulted in greater average normal pressure and shear stress ( p < 0.05). Conclusions: These methods may be useful to aid experimental studies by providing insights into the effects of varied prosthesis design parameters or gait conditions on residual limb-socket interface dynamics. The current results suggest that these effects may be subject-specific., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Michael McGeehan, Kieran Nichols, and Michael Hahn declare no conflicts of interest for this work. Peter Adamczyk was a partner in Intelligent Prosthetic Systems, LLC, which created the Variable Stiffness Prosthesis used in this project., (© The Author(s) 2022.)

Diffusion-weighted MRI (DW-MRI) offers a potential adjunct to dynamic contrast-enhanced MRI to discriminate benign from malignant breast lesions by yielding quantitative information about tissue microstructure. Multi-component modeling of the DW-MRI signal over an extended b -value range (up to 3000 s/mm 2 ) theoretically isolates the slowly diffusing (restricted) water component in tissues. Previously, a three-component restriction spectrum imaging (RSI) model demonstrated the ability to distinguish malignant lesions from healthy breast tissue. We further evaluated the utility of this three-component model to differentiate malignant from benign lesions and healthy tissue in 12 patients with known malignancy and synchronous pathology-proven benign lesions. The signal contributions from three distinct diffusion compartments were measured to generate parametric maps corresponding to diffusivity on a voxel-wise basis. The three-component model discriminated malignant from benign and healthy tissue, particularly using the restricted diffusion C 1 compartment and product of the restricted and intermediate diffusion compartments ( C 1 and C 2 ). However, benign lesions and healthy tissue did not significantly differ in diffusion characteristics. Quantitative discrimination of these three tissue types (malignant, benign, and healthy) in non-pre-defined lesions may enhance the clinical utility of DW-MRI in reducing excessive biopsies and aiding in surveillance and surgical evaluation without repeated exposure to gadolinium contrast.

The development of lightweight portable sensors and algorithms for the identification of gait events at steady-state running speeds can be translated into the real-world environment. However, the output of these algorithms needs to be validated. The purpose of this study was to validate the identification of running gait events using data from Inertial Measurement Units (IMUs) in a semi-uncontrolled environment. Fifteen healthy runners were recruited for this study, with varied running experience and age. Force-sensing insoles measured normal foot-shoe forces and provided a standard for identification of gait events. Three IMUs were mounted to the participant, two bilaterally on the dorsal aspect of the foot and one clipped to the back of each participant’s waistband, approximating their sacrum. The identification of gait events from the foot-mounted IMU was more accurate than from the sacral-mounted IMU. At running speeds <3.57 m s−1, the sacral-mounted IMU identified contact duration as well as the foot-mounted IMU. However, at speeds >3.57 m s−1, the sacral-mounted IMU overestimated foot contact duration. This study demonstrates that at controlled paces over level ground, we can identify gait events and measure contact time across a range of running skill levels.

To report the radiological features of intestinal ascariasis and to review the clinical implications of this re-emerging disease for adult population of the USA. This retrospective observational study involved 12 adult patients, whose radiological examinations disclosed unsuspected presence of ascaris in their intestinal tract. They were evaluated by computed tomography of the abdomen with oral contrast, small bowel series with barium, and magnetic resonance enterography. This series included 7 men and 5 women, who ranged in age from 19 to 72 years (mean age 48 years). The typical configuration of ascaris within the bowel loops was demonstrated on CT of the abdomen in 5 patients, small bowel examination with barium in 3, and by MR enterography in another 4 cases. Our study highlights the radiological appearances of intestinal ascariasis and the clinical implications of this resurging disease. The practicing radiologists should be aware of these findings, particularly when examining patients who have immigrated from or traveled to the endemic regions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Burnsed-Torres, ML, Wichmann, TK, Clayton, ZS, and Hahn, ME. Comparison of the Gauntlet test with standard laboratory measures of aerobic fitness. J Strength Cond Res 36(2): 386-391, 2022-The purpose of this study was to validate whether the Gauntlet test (GT) can accurately estimate individual aerobic endurance performance compared with standard laboratory-based physiological tests. The GT required athletes to complete 5 maximal effort running stages, with a 1-minute break between each stage, with the goal of achieving the best overall time. Eighteen men (n = 9) and women (n = 9) (age, 23.5 ± 4.13 years; body mass index, 23.1 ± 7.62 kg·m-2; 5k time, 22 ± 7 minutes; 10k time, 47 ± 15 minutes; V̇o2max, 52.3 ± 8 ml·kg-1·min-1) completed a lactate threshold test and V̇o2max test (laboratory measures). Four to 14 days later, subjects completed the GT on an outdoor track. Blood lactate (bLa), V̇o2max, and heart rate (HR) were recorded during the laboratory session. Blood lactate, HR, stage completion time, and overall completion time were recorded during the GT. Linear regression correlation analyses revealed a significant inverse association between V̇o2max (mL·kg-1·min-1) and GT completion time (r = -0.88, P < 0.0001). In addition, there were significant correlations between V̇o2max maximum HR and GT maximum HR (r = 0.89, P < 0.0001) and V̇o2max 3-minute post bLa and GT 3-minute post bLa (r = 0.63, P = 0.0029). Sex-specific analysis showed significant inverse associations between female and male GT completion time and V̇o2max (r = -0.70, P = 0.0352; r = -0.94, P < 0.0002). Bland-Altman plots were used to evaluate concordance between GT completion time, V̇o2max, maximum HR, and 3-minute post bLa. Results suggest the GT is a valid assessment to accurately estimate aerobic endurance performance similar to standard laboratory methods., (Copyright © 2021 National Strength and Conditioning Association.)

Diffusion-weighted magnetic resonance imaging (DWI) of the musculoskeletal system has various applications, including visualization of bone tumors. However, DWI acquired with echo-planar imaging is susceptible to distortions due to static magnetic field inhomogeneities. This study aimed to estimate spatial displacements of bone and to examine whether distortion corrected DWI images more accurately reflect underlying anatomy. Whole-body MRI data from 127 prostate cancer patients were analyzed. The reverse polarity gradient (RPG) technique was applied to DWI data to estimate voxel-level distortions and to produce a distortion corrected DWI dataset. First, an anatomic landmark analysis was conducted, in which corresponding vertebral landmarks on DWI and anatomic T 2 -weighted images were annotated. Changes in distance between DWI- and T 2 -defined landmarks (i.e., changes in error) after distortion correction were calculated. In secondary analyses, distortion estimates from RPG were used to assess spatial displacements of bone metastases. Lastly, changes in mutual information between DWI and T 2 -weighted images of bone metastases after distortion correction were calculated. Distortion correction reduced anatomic error of vertebral DWI up to 29 mm. Error reductions were consistent across subjects (Wilcoxon signed-rank p < 10 -20 ). On average (± SD), participants' largest error reduction was 11.8 mm (± 3.6). Mean (95% CI) displacement of bone lesions was 6.0 mm (95% CI 5.0-7.2); maximum displacement was 17.1 mm. Corrected diffusion images were more similar to structural MRI, as evidenced by consistent increases in mutual information (Wilcoxon signed-rank p < 10 -12 ). These findings support the use of distortion correction techniques to improve localization of bone on DWI., (© 2022. The Author(s).)

The purpose of this study was to compare a heuristic feature identification algorithm with output from the Beta Process Auto Regressive Hidden Markov Model (BP-AR-HMM) utilizing minimally sampled (≤ 100 Hz) human locomotion data for identification of gait events prior to their occurrence. Data were collected from 16 participants (21-64 years) using a single gyroscopic sensor in an inertial measurement unit on the dorsum of the foot, across multiple locomotion modes, including level ground walking and running (across speeds 0.8 m s -1 - 3.0 m s -1 ), ramps and stairs. Identification of gait events, initial contact (IC) and toe off (TO) with the heuristic algorithm, was 94% across locomotion modes. The features identified prior to initial contact had a lead time of 186.32 ± 86.70 ms, while TO had a lead time of 63.96 ± 46.30 ms. The BP-AR-HMM identified features that indicated an impending IC and TO with 99% accuracy, with a lead time of 59.41 ± 54.41 ms for IC and 90.79 ± 35.51 ms for TO. These approaches are consistent in their identification of gait events and have the potential to be utilized for classification and prediction of locomotion mode.

Relatively high frontal and transverse plane motion in the lower limbs during running have been thought to play a role in the development of some running-related injuries (RRIs). Increasing step rate has been shown to significantly alter lower limb kinematics and kinetics during running. The purpose of this study was to evaluate the effects of increasing step rate on rearfoot kinematics, and to confirm how ground reaction forces (GRFs) are adjusted with increased step rate. Twenty runners ran on a force instrumented treadmill while marker position data were collected under three conditions. Participants ran at their preferred pace and step rate, then +5% and +10% of their preferred step rate while being cued by a metronome for three minutes each. Sagittal and frontal plane angles for the rearfoot segment, tibial rotation, and GRFs were calculated during the stance phase of running. Significant decreases were observed in sagittal and frontal plane rearfoot angles, tibial rotation, vertical GRF, and anteroposterior GRF with increased step rate compared with the preferred step rate. Increasing step rate significantly decreased peak sagittal and frontal plane rearfoot and tibial rotation angles. These findings may have implications for some RRIs and gait retraining.

Introduction: Simulations based on computational musculoskeletal models are powerful tools for evaluating the effects of potential biomechanical interventions, such as implementing a novel prosthesis. However, the utility of simulations to evaluate the effects of varied prosthesis design parameters on gait mechanics has not been fully realized due to the lack of a readily-available limb loss-specific gait model and methods for efficiently modeling the energy storage and return dynamics of passive foot prostheses. The purpose of this study was to develop and validate a forward simulation-capable gait model with lower-limb loss and a semi-active variable-stiffness foot (VSF) prosthesis., Methods: A seven-segment 28-DoF gait model was developed and forward kinematics simulations, in which experimentally observed joint kinematics were applied and the resulting contact forces under the prosthesis evolved accordingly, were computed for four subjects with unilateral below-knee amputation walking with a VSF., Results: Model-predicted resultant ground reaction force (GRFR) matched well under trial-specific optimized parameter conditions (mean R2: 0.97, RMSE: 7.7% body weight (BW)) and unoptimized (subject-specific, but not trial-specific) parameter conditions (mean R2: 0.93, RMSE: 12% BW). Simulated anterior-posterior center of pressure demonstrated a mean R2 = 0.64 and RMSE = 14% foot length. Simulated kinematics remained consistent with input data (0.23 deg RMSE, R2 > 0.99) for all conditions., Conclusions: These methods may be useful for simulating gait among individuals with lower-limb loss and predicting GRFR arising from gait with novel VSF prostheses. Such data are useful to optimize prosthesis design parameters on a user-specific basis., (Copyright © 2021 by ASME.)

Persons with ankle osteoarthritis (AOA) often seek surgical intervention to alleviate pain and restore function; however, recent research has yielded no superior choice between the two primary options: fusion and replacement. One factor yet to be considered is the effect of footwear on biomechanical outcomes. Comparisons of AOA biomechanics to a normative population are also sparse. The objectives of this study were to (1) determine how footwear uniquely affected gait in persons with ankle fusion and replacement and (2) provide context for AOA biomechanics via comparisons to a healthy adult sample. Thirty-four persons with AOA performed overground walking trials barefoot and shod before surgical intervention and then received either an ankle fusion (n = 14) or replacement (n = 20). Two and/or three years post-surgery, patients returned for gait analysis. Nineteen controls performed the same gait procedures during a single study visit. Spatiotemporal variables and peak angles, internal moments, powers, and forces were calculated to quantify gait behavior. Overall, the two surgical groups performed similarly to each other but demonstrated marked differences from controls both pre- and post-surgery. No significant differences were detected when examining the effect of footwear. The motion of the midfoot with respect to the hindfoot and forefoot may be instrumental in gait biomechanics following an ankle fusion or replacement and should be considered in future investigations., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Malignancies are molecularly complex and become more resistant with each line of therapy. We hypothesized that offering matched, individualized combination therapies to patients with treatment-naïve, advanced cancers would be feasible and efficacious. Patients with newly diagnosed unresectable/metastatic, poor-prognosis cancers were enrolled in a cross-institutional prospective study., Methods: A total of 145 patients were included in the study. Genomic profiling (tissue and/or circulating tumor DNA) was performed in all patients, and PD-L1 immunohistochemistry, tumor mutational burden, and microsatellite status assessment were performed in a subset of patients. We evaluated safety and outcomes: disease-control rate (stable disease for ≥ 6 months or partial or complete response), progression-free survival (PFS), and overall survival (OS)., Results: Seventy-six of 145 patients (52%) were treated, most commonly for non-colorectal gastrointestinal cancers, carcinomas of unknown primary, and hepatobiliary malignancies (53% women; median age, 63 years). The median number of deleterious genomic alterations per patient was 5 (range, 0-15). Fifty-four treated patients (71%) received ≥ 1 molecularly matched therapy, demonstrating the feasibility of administering molecularly matched therapy. The Matching Score, which reflects the percentage of targeted alterations, correlated linearly with progression-free survival (R 2 = 0.92; P = 0.01), and high (≥ 60%) Matching Score was an independent predictor of improved disease control rate [OR 3.31 (95% CI 1.01-10.83), P = 0.048], PFS [HR 0.55 (0.28-1.07), P = 0.08], and OS [HR 0.42 (0.21-0.85), P = 0.02]. Serious adverse event rates were similar in the unmatched and matched groups., Conclusions: Personalized combination therapies targeting a majority of a patient's molecular alterations have antitumor activity as first-line treatment. These findings underscore the feasibility and importance of using tailored N-of-1 combination therapies early in the course of lethal malignancies., Trial Registration: I-PREDICT ( NCT02534675 ) was registered on August 25, 2015., (© 2021. The Author(s).)

Background: Diffusion magnetic resonance imaging (MRI) is integral to detection of prostate cancer (PCa), but conventional apparent diffusion coefficient (ADC) cannot capture the complexity of prostate tissues and tends to yield noisy images that do not distinctly highlight cancer. A four-compartment restriction spectrum imaging (RSI 4 ) model was recently found to optimally characterize pelvic diffusion signals, and the model coefficient for the slowest diffusion compartment, RSI 4 -C 1 , yielded greatest tumor conspicuity., Purpose: To evaluate the slowest diffusion compartment of a four-compartment spectrum imaging model (RSI 4 -C 1 ) as a quantitative voxel-level classifier of PCa., Study Type: Retrospective., Subjects: Forty-six men who underwent an extended MRI acquisition protocol for suspected PCa. Twenty-three men had benign prostates, and the other 23 men had PCa., Field Strength/sequence: A 3 T, multishell diffusion-weighted and axial T2-weighted sequences., Assessment: High-confidence cancer voxels were delineated by expert consensus, using imaging data and biopsy results. The entire prostate was considered benign in patients with no detectable cancer. Diffusion images were used to calculate RSI 4 -C 1 and conventional ADC. Classifier images were also generated., Statistical Tests: Voxel-level discrimination of PCa from benign prostate tissue was assessed via receiver operating characteristic (ROC) curves generated by bootstrapping with patient-level case resampling. RSI 4 -C 1 was compared to conventional ADC for two metrics: area under the ROC curve (AUC) and false-positive rate for a sensitivity of 90% (FPR 90 ). Statistical significance was assessed using bootstrap difference with two-sided α = 0.05., Results: RSI 4 -C 1 outperformed conventional ADC, with greater AUC (mean 0.977 [95% CI: 0.951-0.991] vs. 0.922 [0.878-0.948]) and lower FPR 90 (0.032 [0.009-0.082] vs. 0.201 [0.132-0.290]). These improvements were statistically significant (P < 0.05)., Data Conclusion: RSI 4 -C 1 yielded a quantitative, voxel-level classifier of PCa that was superior to conventional ADC. RSI classifier images with a low false-positive rate might improve PCa detection and facilitate clinical applications like targeted biopsy and treatment planning., Evidence Level: 3 TECHNICAL EFFICACY: Stage 2., (© 2021 International Society for Magnetic Resonance in Medicine.)

Passive energy storage and return (ESR) feet are current performance standard in lower limb prostheses. A recently developed semi-active variable-stiffness foot (VSF) prosthesis balances the simplicity of a passive ESR device with the adaptability of a powered design. The purpose of this study was to model and simulate the ESR properties of the VSF prosthesis. The ESR properties of the VSF were modeled as a lumped parameter overhung beam. The overhung length is variable, allowing the model to exhibit variable ESR stiffness. Foot-ground contact was modeled using sphere-to-plane contact models. Contact parameters were optimized to represent the geometry and dynamics of the VSF and its foam base. Static compression tests and gait were simulated. Simulation outcomes were compared to corresponding experimental data. Stiffness of the model matched that of the physical VSF (R2: 0.98, root-mean-squared error (RMSE): 1.37 N/mm). Model-predicted resultant ground reaction force (GRFR) matched well under optimized parameter conditions (R2: 0.98, RMSE: 5.3% body weight,) and unoptimized parameter conditions (R2: 0.90, mean RMSE: 13% body weight). Anterior-posterior center of pressure matched well with R2 > 0.94 and RMSE < 9.5% foot length in all conditions. The ESR properties of the VSF were accurately simulated under benchtop testing and dynamic gait conditions. These methods may be useful for predicting GRFR arising from gait with novel prostheses. Such data are useful to optimize prosthesis design parameters on a user-specific basis., (Copyright © 2021 by ASME.)

Goal: The purpose of this study was to provide an initial examination of the utility of the Beta Process - Auto Regressive - Hidden Markov Model (BP-AR-HMM) for the prior identification of gait events. A secondary objective was to determine whether the output of the model could be used for classification and prediction of locomotion states., Methods: In this study we utilized the output of the BP-AR-HMM to develop user-independent identification of gait events and gait classification from an idealized three-dimensional acceleration signal. The input acceleration data were collected from two walking (1.4 and 1.6 ms -1 ) and two running (2.6 and 3.0 ms -1 ) steady state speeds, and during two dynamic walk to run and run to walk transitions (1.8-2.4 and 2.4-1.8 ms -1 ) on an instrumented force treadmill., Results: The BP-AR-HMM identified 9 unique states. Of these, two states, 4 and 1, were utilized to estimate initial contact and toe off, respectively. The lead time from the first instance of state 4 to initial contact was 0.13 ± 0.02 s. Similarly, the first instance of state 1 occurred 0.14 ± 0.03 s before toe off. Two other states (3 and 7) were examined for possible utilization in a probabilistic model for the prediction of pending locomotion state transitions., Conclusion: The identification of gait events prior to their occurrence by the BP-AR-HMM appears to be an approach that can minimize the quantity of sensor data in an offline approach. Furthermore, there is evidence it could also be used as a basis to build a probabilistic model to estimate locomotion transitions.

Inertial measurement units (IMUs) are popular tools for estimating biomechanical variables such as peak vertical ground reaction force (GRF v ) and foot-ground contact time (t c ), often by using multiple sensors or predictive models. Despite their growing use, little is known about the effects of varying low-pass filter cutoff frequency, which can affect the magnitude of force-related dependent variables, the accuracy of IMU-derived metrics, or if simpler methods for such estimations exist. The purpose of this study was to investigate the effects of varying low-pass filter cutoff frequency on the correlation of IMU-derived peak GRF v and t c to gold-standard lab-based measurements. Thirty National Collegiate Athletics Association Division 1 cross country runners ran on an instrumented treadmill at a range of speeds while outfitted with a sacral-mounted IMU. A simple method for estimating peak GRF v from the IMU was implemented by multiplying the IMU's vertical acceleration by the runner's body mass. Data from the IMU were low-pass filtered with 5, 10, and 30 Hz cutoffs. Pearson correlation coefficients were used to determine how well the IMU-derived estimates matched gold-standard biomechanical estimations. Correlations ranged from very weak to moderate for peak GRF v and t c . For peak GRF v , the 10 Hz low-pass filter cutoff performed best (r = 0.638), while for t c the 5 Hz cut-off performed best (r = 0.656). These results suggest that IMU-derived estimates of force and contact time are influenced by the low-pass filter cutoff frequency. Further investigations are needed to determine the optimal low-pass filter cutoff frequency or a different method to accurately estimate force and contact time is suggested., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Stress fractures are injuries caused by repetitive loading during activities such as running. The application of advanced analytical methods such as machine learning to data from multiple wearable sensors has allowed for predictions of biomechanical variables associated with running-related injuries like stress fractures. However, it is unclear if data from a single wearable sensor can accurately estimate variables that characterize external loading during running such as peak vertical ground reaction force (vGRF), vertical impulse, and ground contact time. Predicting these biomechanical variables with a single wearable sensor could allow researchers, clinicians, and coaches to longitudinally monitor biomechanical running-related injury risk factors without expensive force-measuring equipment., Purpose: We quantified the accuracy of applying quantile regression forest (QRF) and linear regression (LR) models to sacral-mounted accelerometer data to predict peak vGRF, vertical impulse, and ground contact time across a range of running speeds., Methods: Thirty-seven collegiate cross country runners (24 females, 13 males) ran on a force-measuring treadmill at 3.8-5.4 m/s while wearing an accelerometer clipped posteriorly to the waistband of their running shorts. We cross-validated QRF and LR models by training them on acceleration data, running speed, step frequency, and body mass as predictor variables. Trained models were then used to predict peak vGRF, vertical impulse, and contact time. We compared predicted values to those calculated from a force-measuring treadmill on a subset of data ( n  = 9) withheld during model training. We quantified prediction accuracy by calculating the root mean square error (RMSE) and mean absolute percentage error (MAPE)., Results: The QRF model predicted peak vGRF with a RMSE of 0.150 body weights (BW) and MAPE of 4.27  ±  2.85%, predicted vertical impulse with a RMSE of 0.004 BW*s and MAPE of 0.80  ±  0.91%, and predicted contact time with a RMSE of 0.011 s and MAPE of 4.68  ±  3.00%. The LR model predicted peak vGRF with a RMSE of 0.139 BW and MAPE of 4.04  ±  2.57%, predicted vertical impulse with a RMSE of 0.002 BW*s and MAPE of 0.50  ±  0.42%, and predicted contact time with a RMSE of 0.008 s and MAPE of 3.50  ±  2.27%. There were no statistically significant differences between QRF and LR model prediction MAPE for peak vGRF ( p  = 0.549) or vertical impulse ( p  = 0.073), but the LR model's MAPE for contact time was significantly lower than the QRF model's MAPE ( p  = 0.0497)., Conclusions: Our findings indicate that the QRF and LR models can accurately predict peak vGRF, vertical impulse, and contact time (MAPE < 5%) from a single sacral-mounted accelerometer across a range of running speeds. These findings may be beneficial for researchers, clinicians, or coaches seeking to monitor running-related injury risk factors without force-measuring equipment., Competing Interests: The authors declare there are no competing interests., (©2021 Alcantara et al.)

Background: Multicompartmental modeling outperforms conventional diffusion-weighted imaging (DWI) in the assessment of prostate cancer. Optimized multicompartmental models could further improve the detection and characterization of prostate cancer., Purpose: To optimize multicompartmental signal models and apply them to study diffusion in normal and cancerous prostate tissue in vivo., Study Type: Retrospective., Subjects: Forty-six patients who underwent MRI examination for suspected prostate cancer; 23 had prostate cancer and 23 had no detectable cancer., Field Strength/sequence: 3T multishell diffusion-weighted sequence., Assessment: Multicompartmental models with 2-5 tissue compartments were fit to DWI data from the prostate to determine optimal compartmental apparent diffusion coefficients (ADCs). These ADCs were used to compute signal contributions from the different compartments. The Bayesian Information Criterion (BIC) and model-fitting residuals were calculated to quantify model complexity and goodness-of-fit. Tumor contrast-to-noise ratio (CNR) and tumor-to-background signal intensity ratio (SIR) were computed for conventional DWI and multicompartmental signal-contribution maps., Statistical Tests: Analysis of variance (ANOVA) and two-sample t-tests (α = 0.05) were used to compare fitting residuals between prostate regions and between multicompartmental models. T-tests (α = 0.05) were also used to assess differences in compartmental signal-fraction between tissue types and CNR/SIR between conventional DWI and multicompartmental models., Results: The lowest BIC was observed from the 4-compartment model, with optimal ADCs of 5.2e-4, 1.9e-3, 3.0e-3, and >3.0e-2 mm 2 /sec. Fitting residuals from multicompartmental models were significantly lower than from conventional ADC mapping (P < 0.05). Residuals were lowest in the peripheral zone and highest in tumors. Tumor tissue showed the largest reduction in fitting residual by increasing model order. Tumors had a greater proportion of signal from compartment 1 than normal tissue (P < 0.05). Tumor CNR and SIR were greater on compartment-1 signal maps than conventional DWI (P < 0.05) and increased with model order., Data Conclusion: The 4-compartment signal model best described diffusion in the prostate. Compartmental signal contributions revealed by this model may improve assessment of prostate cancer. Level of Evidence 3 Technical Efficacy Stage 3 J. MAGN. RESON. IMAGING 2021;53:628-639., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background: Modifying the longitudinal bending stiffness (LBS) of footwear has become a popular method to improve sport performance. It has been demonstrated to influence running economy by altering lower extremity joint level mechanics. Previous studies have only examined within-participant effects at one running speed., Research Question: Do joint level mechanics differ in response to varying footwear LBS at a range of running speeds?, Methods: This study utilized a cross-sectional repeated measure study design using a convenience sample. Ten well trained non-rearfoot strike male distance runners ran at 3.89, 4.70, and 5.56 m/s (14, 17, 20 km/hr) in footwear of three different LBS levels. Mechanics and energetics of the metatarsophalangeal joint (MTPJ), ankle, knee, and hip joints during stance phase were assessed using an 8-camera optical motion capture system (f s = 200 Hz), a force instrumented treadmill (f s = 1000 Hz) and standard inverse dynamics theory., Results: Range of motion and negative work decreased and angular stiffness increased for the MTPJ with increasing LBS at all speeds (p < .001). Peak MTPJ moment did not change at any speed in response to increased LBS. Negative work at the ankle decreased in the stiff shoe at 17 km/hr (p = .036). Peak ankle plantar flexion velocity decreased with increasing LBS at all speeds (p < .05)., Significance: While changes in MTPJ mechanics were consistent across speeds, decreased negative ankle work was only observed at 17 km/hr in the stiff shoe, suggesting that perhaps tuned footwear LBS may need to focus primarily on metabolically beneficial changes in ankle plantar flexor mechanical behavior to improve performance in distance runners. Tuning footwear stiffness may also be beneficial to clinical populations, as clinicians seek to optimize their patients' locomotion economy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.

Objectives: To assess the visualization rate and size of the frontal horns (FHs) and cavum septi pellucidi (CSP) in healthy fetuses throughout pregnancy., Methods: After Institutional Review Board approval, 522 consecutive uncomplicated singleton pregnancies between 15 and 39 gestational weeks were enrolled in the study. Ultrasound measurements of the anterior horn width (AHW), center from the horn distance (CFHD), distance from the FHs to the CSP, and CSP width were retrospectively performed using axial transventricular or transcerebellar planes. Available maternal body mass indices were recorded., Results: At least 1 FH was seen in 78% of the cases. The mean AHW decreased over the second trimester and plateaued in the third trimester. The CFHD plateaued in the second trimester and increased in the third trimester. Downside FHs were generally larger than upside FHs. More FHs were measured in transventricular (69%) than transcerebellar (31%) planes. Frontal horns were seen with high, low, and no confidence in 57%, 21%, and 22% of cases, respectively. No-confidence rates were 17% in the second trimester and 42% in the third trimester. The CSP was not visualized in 4% of cases; 15 of 19 cases of a nonvisualized CSP were scanned between 18 and 37 weeks. Mean body mass indices ± SDs were 27.6 ± 6.7 kg/m 2 for the patients in cases of a visualized CSP and 32.4 ± 9.1 kg/m 2 for the patients in cases of a nonvisualized CSP., Conclusions: Normative data for the fetal FH and CSP width were established. Frontal horns are more frequently seen on transventricular views and are difficult to confidently assess in the late third trimester. This study challenges previously reported data that the CSP is seen in 100% of cases from 18 to 37 weeks., (© 2019 by the American Institute of Ultrasound in Medicine.)

The intrinsic foot musculature (IFM) supports the arches of the foot and controls metatarsophalangeal joint (MTPJ) motion. Stronger IFM can increase the effective foot length, potentially altering lower-extremity gearing similar to that of using carbon-fibre-plated footwear. The purpose of this study was to investigate if strengthening of the IFM can alter gait mechanics and improve running economy. Eleven participants were randomly assigned into an experimental group and nine into a control group. The experimental group performed IFM strengthening exercises for ten weeks. Toe-flexor strength, gait mechanics, and running economy were assessed at baseline, five weeks, and ten weeks; using a custom strength testing apparatus, motion capture and force-instrumented treadmill, and indirect calorimetry. Toe-flexor strength increased in the experimental group ( p = .006); however, MTPJ and ankle mechanics and running economy did not change. The dearth of changes in mechanics may be due to a lack of mechanical advantage of the IFM, runners staying within their preferred movement path, a need for MTPJ dorsiflexion to facilitate the windlass mechanism, or the primary function of the IFM being to support the longitudinal arch of the foot as opposed to modulating MTPJ mechanics.

Altering the longitudinal bending stiffness of footwear has the potential to affect mechanics of the metatarsophalangeal (MTP) joint. Recent efforts have been put forth to identify an optimal bending stiffness of footwear to improve running performance. However, little is known about how this optimal bending stiffness may change with running speed. The purpose of this study was to investigate how dynamic angular stiffness about the MTP joint changes across running speeds. Eighteen participants ran at five speeds from 3.89 to 6.11 m/s. Metatarsophalangeal joint angles, moments, and stiffness were estimated for each speed. Two MTPJ load-displacement metrics were defined, active and critical stiffness. Instantaneous stiffness of the MTP joint was also quantified. There was a significant main effect of speed on critical stiffness (p < .001), maximum MTP moment (p < .001), MTP moment at maximum dorsiflexion (p < .001), and MTP range of motion (p = .013). There was no effect of speed on active stiffness (p = .094). These results support the notion that involvement of the MTP joint increases with running speed. Individual contributions of the foot and shoe to the MTP joint moment and stiffness suggest that the foot appears to dominate the stiffness of the foot-shoe complex and torque generation about the MTP joint. Instantaneous stiffness fluctuated throughout stance phase, suggesting that foot-shoe complex stiffness is time dependent. The ratio by which critical stiffness and MTP joint range of motion increase with running speed may provide insight for how to guide construction of performance footwear. These results suggest that when utilizing MTP joint mechanics for insights into designing a shoe for performance purposes, the effect of speed should be taken into consideration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cancer treatments have evolved from indiscriminate cytotoxic agents to selective genome- and immune-targeted drugs that have transformed the outcomes of some malignancies 1 . Tumor complexity and heterogeneity suggest that the 'precision medicine' paradigm of cancer therapy requires treatment to be personalized to the individual patient 2-6 . To date, precision oncology trials have been based on molecular matching with predetermined monotherapies 7-14 . Several of these trials have been hindered by very low matching rates, often in the 5-10% range 15 , and low response rates. Low matching rates may be due to the use of limited gene panels, restrictive molecular matching algorithms, lack of drug availability, or the deterioration and death of end-stage patients before therapy can be implemented. We hypothesized that personalized treatment with combination therapies would improve outcomes in patients with refractory malignancies. As a first test of this concept, we implemented a cross-institutional prospective study (I-PREDICT, NCT02534675 ) that used tumor DNA sequencing and timely recommendations for individualized treatment with combination therapies. We found that administration of customized multidrug regimens was feasible, with 49% of consented patients receiving personalized treatment. Targeting of a larger fraction of identified molecular alterations, yielding a higher 'matching score', was correlated with significantly improved disease control rates, as well as longer progression-free and overall survival rates, compared to targeting of fewer somatic alterations. Our findings suggest that the current clinical trial paradigm for precision oncology, which pairs one driver mutation with one drug, may be optimized by treating molecularly complex and heterogeneous cancers with combinations of customized agents.

Progression of age can influence gait characteristics. Previous research has investigated lower extremity joint mechanics between young and elderly people in locomotion, however little is known about whether differences exist between young and middle age people. Ten young healthy subjects (22.8 ± 5.3 years) and ten middle age healthy subjects (50.7 ± 6.0 years) engaged in treadmill walking (from 0.8 to 2.0 m/s) and running (from 1.8 to 3.8 m/s). The middle age group had higher ankle plantar flexor moment angular impulse (p = 0.002), total support moment impulse (p = 0.016), and hip stance positive work (p = 0.029) across walking speeds. Additionally, the middle age group had higher knee flexion angle at ground contact in walking (p = 0.005) and running (p = 0.037). These findings indicate that moderate age affects changes in ankle and hip kinetic characteristics in walking, and knee kinematic patterns in both walking and running.

The forefoot functions as the base of support during late stance, rotating about the dual-axis of the metatarsophalangeal joints. Previous research has shown that joint axis definition affects estimated joint moments about the forefoot. However, little is known about how metatarsophalangeal joint center definition affects estimated joint kinetics. This study compared moments about the metatarsophalangeal joint using four different defined joint centers. There was a significant difference (p < .001) in peak moments between joint center definitions, differing by up to 0.488 N-m/kg for the slow and 0.878 N-m/kg for the fast running speeds tested. Additionally, there was a significant difference (p < .001) for when peak plantar flexor moment occurred during the slower running condition. The more posteriorly oriented joint centers resulted in higher moments and earlier onset of the plantar flexor moment. In addition to careful modeling of the metatarsophalangeal joint axis, it is recommended that joint center definition should be considered as well., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Gait adaptation is a task that requires fine-tuned coordination of all degrees of freedom in the lower limbs by the central nervous system. However, when individuals change their gait it is unknown how this coordination is organized, and how it can be influenced by contextual interference during practice. Such knowledge could provide information about measurement of gait adaptation during rehabilitation. Able-bodied individuals completed an acute bout of asymmetric split-belt treadmill walking, where one limb was driven at a constant velocity and the other according to one of three designed practice paradigms: serial practice, where the variable limb belt velocity increased over time; random blocked practice, where every 20 strides the variable limb belt velocity changed randomly; random practice, where every stride the variable limb belt velocity changed randomly. On the second day, subjects completed one of two different transfer tests; one with a belt asymmetry close to that experienced on the acquisition day (transfer 1; 1.5:1), and one with a greater asymmetry (transfer 2; 2:1) . To reduce this inherently high-dimensional dataset, principal component analyses were used for kinematic data collected throughout the acquisition and transfer phases; resulting in extraction of the first two principal components (PCs). For acquisition, PC1 and PC2 were related to sagittal and frontal plane control. For transfer 1, PC1 and PC2 were related to frontal plane control of the base of support and whole-body center of mass. For transfer 2, PC1 did not have any variables with high enough coefficients deemed to be relevant, and PC2 was related to sagittal plane control. Observations of principal component scores indicate that variance structuring differs among practice groups during acquisition and transfer 1, but not transfer 2. These results demonstrate the main kinematic coordinative structures that exist during gait adaptation, and that control of sagittal plane and frontal plane motion are perhaps a trade-off during acquisition of a novel asymmetric gait pattern., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: End-stage ankle arthritis is a debilitating condition that often requires surgical intervention after failed conservative treatments. Ankle arthrodesis is a common surgical option, especially for younger and highly active patients; however, ankle arthroplasty has become increasingly popular as advancements in implant design improve device longevity. The longitudinal differences in biomechanical outcomes between these surgical treatments remain indistinct, likely due to the challenges associated with objective study of a heterogeneous population., Methods: Patients scheduled for arthroplasty (n = 27) and arthrodesis (n = 20) were recruited to participate in this three-year prospective study. Postoperative functional outcomes were compared at distinct annual time increments using measures of gait analysis, average daily step count and survey score., Findings: Both surgical groups presented reduced pain, improved survey scores, and increased walking speed at the first-year postoperative session, which were generally consistent across the three-year follow-up. Arthrodesis patients walked with decreased sagittal ankle RoM, increased sagittal hip RoM, increased step length, and increased transient force at heel strike, postoperatively. Arthroplasty patients increased ankle RoM and cadence, with no changes in hip RoM, step length or heel strike transient force., Interpretation: Most postoperative changes were detected at the first-year follow-up session and maintained across the three-year time period. Despite generally favorable outcomes associated with both surgeries, several underlying postoperative biomechanical differences were detected, which may have long-term functional consequences. Furthermore, neither technique was able to completely restore gait biomechanics to the levels of the contralateral unaffected limb, leaving potential for the development of improved surgical and rehabilitative treatments., (Published by Elsevier Ltd.)

Locomotion task and speed changes affect dynamic joint function. Walking and running require different coordination patterns of lower extremity joint mechanics. These coordination differences can result in measurable changes in kinematic and kinetic patterns. When locomotion speed changes, the functional role and movement strategy of each joint is altered. A deeper understanding of joint level mechanics and functional interactions will benefit rehabilitation programs and assistive device development. In this study, joint stiffness, joint mechanical work and power were assessed, as they relate to dynamic function of joints during locomotion. Ten young healthy subjects (5 males, 5 females) participated in a treadmill walking (0.8-2.0 m/s) and running (1.8-3.8 m/s) study. When running speed increased, the stiffness of all three joints tended to increase. The ankle joint played a dominant role during the stance phase of running, generating more positive work than the knee (p = .003) and hip (p = .0001). The knee and hip joint were more dominant in walking and running swing phase energy absorption and generation, respectively. When locomotion speeds increased, stance phase ankle positive work, swing phase knee negative work, and hip joint positive work tended to increase. These findings suggest that change of locomotion speed or task results in definitive changes to lower extremity joint level mechanics patterns., (Copyright © 2018 Elsevier B.V. All rights reserved.)

When humans make errors in stepping during walking due to a perturbation, they may adapt their gait as a way to correct for discrepancies between predicted and actual sensory feedback. This study sought to determine if increased contextual interference during acquisition of a novel asymmetric gait pattern would change lower-limb mechanical strategies generalized to different walking contexts. Such knowledge could help to clarify the role of contextual interference in locomotor adaptation, and demonstrate potential use in future gait rehabilitation paradigms. One belt on a split-belt treadmill was driven at a constant velocity while the other was driven at changing velocities according to one of three practice paradigms: serial, random blocked, or random training. Subjects returned to complete one of two different transfer tests. Results indicate that during acquisition, random practice requires unique gait mechanics to adapt to a challenging walking environment. Also, results from one transfer test close to that of the acquisition experience did not seem to demonstrate any contextual interference effect. Finally, random blocked practice resulted in highly unique changes in step length symmetry on a second, more challenging, transfer test. This perhaps indicates that a moderate level of contextual interference causes unique locomotor generalization strategies., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Very little is known about the effects of specific practice on motor learning of predictive balance control during novel bipedal gait. This information could provide an insight into how the direction and magnitude of predictive errors during acquisition of a novel gait task influence transfer of balance control, as well as yield a practice protocol for the restoration of balance for those with locomotor impairments. This study examined the effect of a variable practice paradigm on transfer of a novel asymmetric gait pattern in able-bodied individuals. Using a split-belt treadmill, one limb was driven at a constant velocity (constant limb) and the other underwent specific changes in velocity (variable limb) during practice according to one of three prescribed practice paradigms: serial, where the variable limb velocity increased linearly; random blocked, where variable limb underwent random belt velocity changes every 20 strides; and random practice, where the variable limb underwent random step-to-step changes in velocity. Random practice showed the highest balance control variability during acquisition compared to serial and random blocked practice which demonstrated the best transfer of balance control on one transfer test. Both random and random blocked practices showed significantly less balance control variability during a second transfer test compared to serial practice. These results indicate that random blocked practice may be best for generalizability of balance control while learning a novel gait, perhaps, indicating that individuals who underwent this practice paradigm were able to find the most optimal balance control solution during practice.

Many studies have reported the effects of different foot prostheses on gait, but most results cannot be generalized because the prostheses' properties are seldom reported. We varied hindfoot and forefoot stiffness in an experimental foot prosthesis, in increments of 15N/mm, and tested the parametric effects of these variations on treadmill walking in unilateral transtibial amputees, at speeds from 0.7 to 1.5m/s. We computed outcomes such as prosthesis energy return, center of mass (COM) mechanics, ground reaction forces, and joint mechanics, and computed their sensitivity to component stiffness. A stiffer hindfoot led to reduced prosthesis energy return, increased ground reaction force (GRF) loading rate, and greater stance-phase knee flexion and knee extensor moment. A stiffer forefoot resulted in reduced prosthetic-side ankle push-off and COM push-off work, and increased knee extension and knee flexor moment in late stance. The sensitivity parameters obtained from these tests may be useful in clinical prescription and further research into compensatory mechanisms of joint function., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate whether lower extremity muscle activation patterns differ in the strides leading to locomotive state transitions in the involved limb of individuals with transtibial amputation. It is hypothesized that all transitions elicit activation differences between strides as the subjects move toward the transition event., Design: Single-sample, observational study., Setting: University research center., Participants: Volunteer sample of persons with unilateral transtibial amputation (N=9; mean age, 48.8±12.1y; mean height, 1.74±0.09m; mean weight, 86.1±24.7kg) were recruited by posting flyers in local prosthetics clinics., Interventions: Not applicable., Main Outcome Measures: Surface electromyography was used to measure muscle activation from 7 muscles of the involved limb. Subjects walked across 8 different terrain conditions transitioning from level-ground to ramp/stair locomotion and vice versa. Statistical Parametric Mapping analysis of variance (α<.05) was used to assess muscle activation differences in the 3 pretransition gait cycles as subjects moved toward the terrain change., Results: No muscle activation changes were observed in ramp transitions. All stair transitions elicited a myoelectric difference in at least 2 muscles. The transition from stair descent to level ground elicited change in the greatest number of muscles. Tibialis anterior activation was unchanged in all transitions., Conclusions: Muscle activation differences were observed in the involved limb of individuals with transtibial amputation during stair transitions, suggesting that those patterns may be successfully used in transition detection algorithms. It remains unknown whether ramp transitions can be successfully identified pretransition using electromyography., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Unilateral hand contractions increase activation in the motor cortex of the contralateral hemisphere, providing a means to alter the relative degree of activation in the right hemisphere versus the left hemisphere through spreading activation. Prior research reported enhanced verbal creativity as measured by performance on remote associate problems in Hebrew from left-hand contractions (right-hemisphere activation). We sought to extend the previous findings to English problems and to homograph interpretation. In Experiment 1, unilateral hand contractions in fact altered performance on the English remote associates, but in the direction of improved performance following right-hand contractions and left-hemisphere activation. In Experiment 2, the probability of retrieving atypical interpretations of homographs with multiple meanings was least likely for left-hemisphere dominant strong right handers, but the hand contraction manipulation had no effect.

Gait termination can be challenging for balance-impaired populations, including lower limb amputees. As powered prosthetic ankle devices come to market, it is important to better understand gait termination timing in an unplanned situation. Timing patterns were examined in unplanned gait termination to determine a threshold for being able to terminate gait in 1 step. Time to terminate gait (TTG) was also examined, using both final heel strike and center of mass (COM) acceleration metrics. Fourteen able-bodied subjects walked over ground and terminated gait in response to a randomly-timed auditory stimulus. A lumbar-mounted accelerometer and footswitches were used to assess timing of gait termination. Subjects were able to terminate gait in 1 step if the stimulus occurred at or before 19.8% of gait cycle. Later stimulus resulted in a 2-step stop pattern. The TTG using COM acceleration was greater than when using heel strike data. Motion of the COM was not fully arrested until 162 ± 38% of gait cycle. The stabilization phase between heel strike and COM motion arrest was greater for 1-step stops (1.41 ± 0.42 s) than 2-step stops (0.96 ± 0.33 s). These findings indicate gait termination timing should be calculated using COM motion, including the stabilization phase post heel strike.