Effect of Level of Urology Training on Gleason Score and Prostate Volume Estimation Agreement between Transrectal Ultrasound Guided Biopsy and Radical Prostatectomy Specimen

Introduction Transrectal ultrasound guided prostate biopsy may be performed by operators with various levels of training. Little is known about the impact of training level on biopsy results. We evaluated the effect of training level on the accuracy of transrectal ultrasound guided prostate biopsy findings. Methods We retrospectively reviewed 500 consecutive patients who underwent transrectal ultrasound guided prostate biopsy and subsequent radical prostatectomy. Transrectal ultrasound operators were stratified based on level of training as junior, senior, chief, fellow or staff. Linear regression was performed to analyze the effect of training level on volume estimates. A weighted Kappa statistic evaluated agreement between biopsy and pathological Gleason scores while an adjusted cumulative logistic regression model analyzed the effects of training level. Results A total of 482 patients were included in the final analysis. Transrectal ultrasound guided biopsy was performed by staff in 78 (16%) patients, by fellows in 18 (4%), chief residents in 48 (10%), senior residents in 126 (26%) and junior residents in 212 (44%). There was no significant difference between transrectal ultrasound and radical prostatectomy specimen volume estimates among the training levels. Level of training was not significantly associated with pathological features, including Gleason score, primary Gleason grade, highest single Gleason grade and estimated tumor volume. Study limitations include the retrospective design and the variability among members of the same group. Conclusions Agreement between biopsy and pathological Gleason scores is high for all levels of training. Training level has no impact on prostate volume estimations or the prediction of pathological features

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

Salinity variations in the northern Coorong Lagoon, South Australia: Significant changes in the ecosystem following human alteration to the natural water regime

European settlement and drought have significantly impacted the hydrology of the Coorong, a shallow coastal lagoon complex in South Australia, which is part of a terminal wetland at the mouth of the River Murray. An increased salinity associated with lower water levels and progressive isolation from ocean flushes contributed to a severe decline in ecological diversity over the past decades. Here we have conducted a molecular and stable isotopic study of a sedimentary core from the northern Coorong Lagoon spanning more than 5000 years to investigate the recent palaeoenvironmental history of the ecosystem. Major alterations were evident in many biogeochemical parameters in sediments deposited after the 1950s coinciding with the beginning of intensified water regulations. The most prominent shift occurred in δ13C profiles of C21–C33n-alkanes from average values of −23.5‰ to an average of −28.2‰.Further changes included decreases in carbon preference index (CPI) and average chain length (ACL) of the n-alkane series as well as significant increases in algal (e.g. C20 HBI, long chain alkenes and C29-alkadiene) and bacterial (e.g. 13C depleted short chain n-alkanes and hopanoids, δ13C: −35.9‰ to −30.1‰) derived hydrocarbons. Long chain n-alkanes with a strong odd/even predominance as observed here are typically attributed to terrigenous plants. In the Coorong however, terrigenous input to sedimentary OM is only minor. Therefore changes in the before mentioned parameters were attributed to a source transition from a major contribution of macrophytes towards predominantly microalgae and bacteria.δD values of C21–C33n-alkanes showed a general trend towards more enriched values in younger sediments, indicating an overall rising salinity. However, the most pronounced positive shift in these profiles again occurred after the 1950s. Altogether this study demonstrates that the recent human induced changes of the Coorong hydrology, compounded by a severe drought led to an increase in salinity and alterations of primary production which have been much more significant than natural variations occurring throughout the Holocene over several thousands of years

A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats

A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats. After immunization of mice with partially-purified heparan sulfate proteoglycan (HSPG) isolated from rat glomeruli, a monoclonal antibody (mAb JM-403) was obtained, which was directed against heparan sulfate (HS), the glycosaminoglycan side chain of HSPG. In ELISA it reacted with isolated human glomerular basement membrane (GBM) HSPG, HS and hyaluronic acid, but not with the core protein of human GBM HSPG, and not with chondroitin sulfate A and C, dermatan sulfate, keratan sulfate and heparin. Furthermore, it did not bind to laminin, collagen type IV or fibronectin. Specificity of JM-403 for HS was also suggested by results of inhibition studies, which found that intact HSPG and HS, but not the core protein, inhibited the binding of JM-403 to HS. In indirect immunofluorescence on cryostat sections of rat kidney, a fine granular to linear staining of the GBM was observed, along with a variable staining of the other renal basement membranes. Pretreatment of the sections with heparitinase completely prevented the binding of mAb JM-403, whereas pretreatment with chondroitinase ABC or hyaluronidase had no effect. The precise binding site of mAb JM-403 was investigated by indirect immunoelec-tron microscopy. It revealed a diffuse staining of the whole width of the GBM. One hour after intravenous injection of JM-403 into rats, the mAb was detected along the glomerular capillary wall in a fine granular pattern, which shifted towards a more mesangial localization after 24 hours. No binding was observed anymore by day 15. Intravenous injection induced a dose-dependent, transient and selective proteinuria that was maximal immediately after the injection. Administration of 2 mg of JM-403 increased the urinary albumin excretion within the first 24 hours after injection from (mean ± SD) 177 ± 19 to 20,755 ± 10,310 µg/24 hr (P < 0.01); the urinary IgG excretion increased from 5.8 ± 2.9 to 236.1 ± 132.2 µg/24 hr (P < 0.03); the selectivity index (clearance IgG/clearance albumin) decreased from 0.33 ± 0.12 to 0.12 ± 0.05 (P < 0.004)

Two degree-of-freedom hysteresis compensation for a dynamic mirror with antagonistic piezoelectric stack actuation

A dynamic mirror actuator (DMA) with antagonistic piezoelectric stack actuation (PESA) is considered for laser beam dot placement error reduction in electrophotographic processes. The DMA is required to meet tracking error specifications below 500~Hz to reduce low-frequency process noise and base vibration. In addition, the DMA is desired to compensate repeatable high-frequency tracking errors due to polygon mirror facet-to-facet misalignment. This high-frequency error correction is a new and novel problem. The development of the DMA is approached in two steps: development of a linear model and low-computation, high-bandwidth hysteresis control. First, a methodology for development of the best linear model to represent the DMA is presented. The DMA is known to exhibit hysteresis and other nonlinearities which are represented by additive input uncertainty and feedback uncertainty elements, respectively, connected to the linear plant model. The proposed linear model employs explicit PESA charging dynamics and incorporates two drive modes for mapping a single control input to the two PESA drive voltages. The proposed linear model is compared to constitutive models from literature and shown to exhibit less frequency response error when compared to experimental data. As a further validation, simulated step response data is shown to agree with experimental data. Second, a methodology for designing a low-computation, high-bandwidth strategy for closed-loop hysteresis control of the DMA without a priori knowledge of the desired trajectory is presented. The resulting hysteresis control is applied to the DMA. A hysteresis compensator is created as a finite state machine switching among polynomials for hysteresis inversion along rising or falling curves. Residual hysteresis error after compensation is further corrected by an LQR feedback controller. Experimental results demonstrate effectiveness of the hysteresis compensator and closed-loop system under the proposed hysteresis control strategy. For the triangular input signal tested, the closed-loop system achieves a 91.5% reduction in hysteresis uncertainty