The International Society of Urological Pathology (ISUP) revised the Gleason system in 2005 and 2014. The impact of these changes on prostate cancer (PCa) prognostication remains unclear.
To evaluate ...if the ISUP 2014 Gleason score (GS) predicts PCa death better than the pre-2005 GS, and if additional histopathological information can further improve PCa death prediction.
We conducted a case-control study nested among men in the National Prostate Cancer Register of Sweden diagnosed with non-metastatic PCa 1998-2015. We included 369 men who died from PCa (cases) and 369 men who did not (controls). Two uro-pathologists centrally re-reviewed biopsy ISUP 2014 Gleason grading, poorly formed glands, cribriform pattern, comedonecrosis, perineural invasion, intraductal, ductal and mucinous carcinoma, percentage Gleason 4, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and post-atrophic hyperplasia. Pre-2005 GS was back-transformed using i) information on cribriform pattern and/or poorly formed glands and ii) the diagnostic GS from the registry. Models were developed using Firth logistic regression and compared in terms of discrimination (AUC).
The ISUP 2014 GS (AUC = 0.808) performed better than the pre-2005 GS when back-transformed using only cribriform pattern (AUC = 0.785) or both cribriform and poorly formed glands (AUC = 0.792), but not when back-transformed using only poorly formed glands (AUC = 0.800). Similarly, the ISUP 2014 GS performed better than the diagnostic GS (AUC = 0.808 vs 0.781). Comedonecrosis (AUC = 0.811), HGPIN (AUC = 0.810) and number of cores with ≥50% cancer (AUC = 0.810) predicted PCa death independently of the ISUP 2014 GS.
The Gleason Grading revisions have improved PCa death prediction, likely due to classifying cribriform patterns, rather than poorly formed glands, as Gleason 4. Comedonecrosis, HGPIN and number of cores with ≥50% cancer further improve PCa death discrimination slightly.
Abstract The hamstring muscles frequently suffer injury during high-speed running, though the factors that make an individual more susceptible to injury remain poorly understood. The goals of this ...study were to measure the musculotendon dimensions of the biceps femoris long head (BFlh) muscle, the hamstring muscle injured most often, and to use computational models to assess the influence of variability in the BFlh’s dimensions on internal tissue strains during high-speed running. High-resolution magnetic resonance (MR) images were acquired over the thigh in 12 collegiate athletes, and musculotendon dimensions were measured in the proximal free tendon/aponeurosis, muscle and distal free tendon/aponeurosis. Finite element meshes were generated based on the average, standard deviation and range of BFlh dimensions. Simulation boundary conditions were defined to match muscle activation and musculotendon length change in the BFlh during high-speed running. Muscle and connective tissue dimensions were found to vary between subjects, with a coefficient of variation (CV) of 17±6% across all dimensions. For all simulations peak local strain was highest along the proximal myotendinous junction, which is where injury typically occurs. Model variations showed that peak local tissue strain increased as the proximal aponeurosis width narrowed and the muscle width widened. The aponeurosis width and muscle width variation models showed that the relative dimensions of these structures influence internal muscle tissue strains. The results of this study indicate that a musculotendon unit’s architecture influences its strain injury susceptibility during high-speed running.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Complex sensor arrays prohibit practical deployment of existing wearables-based algorithms for free-living analysis of muscle and joint mechanics. Machine learning techniques have been proposed as a ...potential solution, however, they are less interpretable and generalizable when compared to physics-based techniques. Herein, we propose a hybrid method utilizing inertial sensor- and electromyography (EMG)-driven simulation of muscle contraction to characterize knee joint and muscle mechanics during walking gait. Machine learning is used only to map a subset of measured muscle excitations to a full set thereby reducing the number of required sensors. We demonstrate the utility of the approach for estimating net knee flexion moment (KFM) as well as individual muscle moment and work during the stance phase of gait across nine unimpaired subjects. Across all subjects, KFM was estimated with 0.91%BW*H RMSE and strong correlations ( r = 0.87) compared to ground truth inverse dynamics analysis. Estimates of individual muscle moments were strongly correlated ( r = 0.81-0.99) with a reference EMG-driven technique using optical motion capture and a full set of electrodes as were estimates of muscle work ( r = 0.88-0.99). Implementation of the proposed technique in the current work included instrumenting only three muscles with surface electrodes (lateral and medial gastrocnemius and vastus medialis) and both the thigh and shank segments with inertial sensors. These sensor locations permit instrumentation of a knee brace/sleeve facilitating a practically deployable mechanism for monitoring muscle and joint mechanics with performance comparable to the current state-of-the-art.
A regional probabilistic model for the estimation of medium-high return period flood quantiles is presented. The model is based on the use of theoretically derived probability distributions of annual ...maximum flood peaks (DDF). The general model is called TCIF (Two-Component IF model) and encompasses two different threshold mechanisms associated with ordinary and extraordinary events, respectively. Based on at-site calibration of this model for 33 gauged sites in Southern Italy, a regional analysis is performed obtaining satisfactory results for the estimation of flood quantiles for return periods of technical interest, thus suggesting the use of the proposed methodology for the application to ungauged basins. The model is validated by using a jack-knife cross-validation technique taking all river basins into consideration.
A Mach–Zehnder interferometer is a basic building block for linear transformations that has been widely applied in optical neural networks. However, its sinusoidal transfer function leads to the ...inevitable dynamic phase quantization error, which is hard to eliminate through pre-calibration. Here, a strongly overcoupled ring is introduced to compensate for the phase change without adding perceptible loss. Two full-scale linearized Mach–Zehnder interferometers are proposed and experimentally validated to improve the bit precision from 4-bit to 6- and 7-bit, providing ∼3.5× to 6.1× lower phase quantization errors while maintaining the same scalability. The corresponding optical neural networks demonstrate higher training accuracy.
Brucella abortus M1-
luc is a mutant strain derived from S19 vaccine strain in which most of
bp26 sequence has been replaced by the luciferase coding gene. Strain I2 is a double mutant derived from ...M1-
luc in which most of
omp19 has been deleted without introduction of any genetic markers. In BALB/c mice, M1-
luc presented equivalent performance to S19 regarding persistence, splenomegaly and protection against challenge. Interestingly, I2 was more attenuated than S19, with no reduction of protection against challenge. In order to evaluate the potential for vaccine use of these strains in the natural host, four groups of 15 heifers, 6-month old, were either non-vaccinated or vaccinated with S19, M1-
luc or I2. To at reached 17-month old, heifers were synchronized with two doses of PGF2α and received natural service during 60 days with two bulls. Pregnant heifers were challenged at approximately six gestation months with virulent
B. abortus S2308. Blood samples post-challenge of heifers were collected for serologic test as well as specimens of aborted fetuses and premature calves for bacterial isolation and histopathological analyses. Protection levels against abortion were 78.6% for S19, 81.8% for M1-
luc and 45.5% for I2, compared to the 25% that did not abort from the non-vaccinated group. These results indicate that in bovines BP26 had no influence in protective capacity of S19, correlating with the results obtained in mice. However, contrarily to what was previously observed in mice, lack of expression of Omp19 rendered in less protection capacity of S19 in the natural host.
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Bone imaging known as DXA ("dexa")-dual energy x-ray absorptiometry of the central skeleton--is considered the "gold standard" test for osteoporosis, which affects more than fifty million Americans. ...The tests are associated with improved clinical outcomes through preventing bone fractures. Cuts in Medicare Part B reimbursement for the provision of this preventive imaging in a physician's office began in 2007 and reached 56 percent below the 2006 level in January 2010. To encourage the use of DXA testing, the Affordable Care Act of 2010 provided partial relief from the cuts for two years (2010-11). Our study found that after a decade of growth, DXA testing in all Part B settings plateaued in 2007-09, resulting in 800,000 fewer tests than expected for Medicare beneficiaries--tests that might have prevented approximately 12,000 fractures. Testing declined in 2010, when the start of reimbursement relief under the Affordable Care Act was delayed, and increased outpatient testing failed to offset reduced use in physician offices. Our findings strongly suggest that the payment cuts reduced beneficiary access and that the tests were underused by elderly female Medicare beneficiaries despite strong association with fracture prevention. We recommend that Congress extend the payment relief granted under the Affordable Care Act for at least another two years.
The present paper introduces an analytical approach for the description of the soil water balance dynamics over a schematic river basin. The model is based on a stochastic differential equation where ...the rainfall forcing is interpreted as an additive noise in the soil water balance. This equation can be solved assuming known the spatial distribution of the soil moisture over the basin transforming the two-dimensional problem in space in a one dimensional one. This assumption is particularly true in the case of humid and semihumid environments, where spatial redistribution becomes dominant producing a well defined soil moisture pattern. The model allowed to derive the probability density function of the saturated portion of a basin and of its relative saturation. This theory is based on the assumption that the soil water storage capacity varies across the basin following a parabolic distribution and the basin has homogeneous soil texture and vegetation cover. The methodology outlined the role played by the soil water storage capacity distribution of the basin on soil water balance. In particular, the resulting probability density functions of the relative basin saturation were found to be strongly controlled by the maximum water storage capacity of the basin, while the probability density functions of the relative saturated portion of the basin are strongly influenced by the spatial heterogeneity of the soil water storage capacity. Moreover, the saturated areas reach their maximum variability when the mean rainfall rate is almost equal to the soil water loss coefficient given by the sum of the maximum rate of evapotranspiration and leakage loss in the soil water balance. The model was tested using the results of a continuous numerical simulation performed with a semi-distributed model in order to validate the proposed theoretical distributions.
Sprint runners achieve much higher gait velocities and accelerations than average humans, due in part to large forces generated by their lower limb muscles. Various factors have been explored in the ...past to understand sprint biomechanics, but the distribution of muscle volumes in the lower limb has not been investigated in elite sprinters. In this study, we used non‐Cartesian MRI to determine muscle sizes in vivo in a group of 15 NCAA Division I sprinters. Normalizing muscle sizes by body size, we compared sprinter muscles to non‐sprinter muscles, calculated Z‐scores to determine non‐uniformly large muscles in sprinters, assessed bilateral symmetry, and assessed gender differences in sprinters' muscles. While limb musculature per height‐mass was 22% greater in sprinters than in non‐sprinters, individual muscles were not all uniformly larger. Hip‐ and knee‐crossing muscles were significantly larger among sprinters (mean difference: 30%, range: 19–54%) but only one ankle‐crossing muscle was significantly larger (tibialis posterior, 28%). Population‐wide asymmetry was not significant in the sprint population but individual muscle asymmetries exceeded 15%. Gender differences in normalized muscle sizes were not significant. The results of this study suggest that non‐uniform hypertrophy patterns, particularly large hip and knee flexors and extensors, are advantageous for fast sprinting.
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BFBNIB, FSPLJ, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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