Accuracy of elastic fusion biopsy in daily practice: results of a multicenter study of 2115 patients

OBJECTIVES: To assess the accuracy of Koelis fusion biopsy for the detection of prostate cancer and clinically significant prostate cancer in the everyday practice. METHODS: We retrospectively enrolled 2115 patients from 15 institutions in four European countries undergoing transrectal Koelis fusion biopsy from 2010 to 2017. A variable number of target (usually 2-4) and random cores (usually 10-14) were carried out, depending on the clinical case and institution habits. The overall and clinically significant prostate cancer detection rates were assessed, evaluating the diagnostic role of additional random biopsies. The cancer detection rate was correlated to multiparametric magnetic resonance imaging features and clinical variables. RESULTS: The mean number of targeted and random cores taken were 3.9 (standard deviation 2.1) and 10.5 (standard deviation 5.0), respectively. The cancer detection rate of Koelis biopsies was 58% for all cancers and 43% for clinically significant prostate cancer. The performance of additional, random cores improved the cancer detection rate of 13% for all cancers (P < 0.001) and 9% for clinically significant prostate cancer (P < 0.001). Prostate cancer was detected in 31%, 66% and 89% of patients with lesions scored as Prostate Imaging Reporting and Data System 3, 4 and 5, respectively. Clinical stage and Prostate Imaging Reporting and Data System score were predictors of prostate cancer detection in multivariate analyses. Prostate-specific antigen was associated with prostate cancer detection only for clinically significant prostate cancer. CONCLUSIONS: Koelis fusion biopsy offers a good cancer detection rate, which is increased in patients with a high Prostate Imaging Reporting and Data System score and clinical stage. The performance of additional, random cores seems unavoidable for correct sampling. In our experience, the Prostate Imaging Reporting and Data System score and clinical stage are predictors of prostate cancer and clinically significant prostate cancer detection; prostate-specific antigen is associated only with clinically significant prostate cancer detection, and a higher number of biopsy cores are not associated with a higher cancer detection rate

Galileo dust data from the jovian system: 2000 to 2003

The Galileo spacecraft was orbiting Jupiter between Dec 1995 and Sep 2003. The Galileo dust detector monitored the jovian dust environment between about 2 and 370 R_J (jovian radius R_J = 71492 km). We present data from the Galileo dust instrument for the period January 2000 to September 2003. We report on the data of 5389 particles measured between 2000 and the end of the mission in 2003. The majority of the 21250 particles for which the full set of measured impact parameters (impact time, impact direction, charge rise times, charge amplitudes, etc.) was transmitted to Earth were tiny grains (about 10 nm in radius), most of them originating from Jupiter's innermost Galilean moon Io. Their impact rates frequently exceeded 10 min^-1. Surprisingly large impact rates up to 100 min^-1 occurred in Aug/Sep 2000 when Galileo was at about 280 R_J from Jupiter. This peak in dust emission appears to coincide with strong changes in the release of neutral gas from the Io torus. Strong variability in the Io dust flux was measured on timescales of days to weeks, indicating large variations in the dust release from Io or the Io torus or both on such short timescales. Galileo has detected a large number of bigger micron-sized particles mostly in the region between the Galilean moons. A surprisingly large number of such bigger grains was measured in March 2003 within a 4-day interval when Galileo was outside Jupiter's magnetosphere at approximately 350 R_J jovicentric distance. Two passages of Jupiter's gossamer rings in 2002 and 2003 provided the first actual comparison of in-situ dust data from a planetary ring with the results inferred from inverting optical images.Comment: 59 pages, 13 figures, 6 tables, submitted to Planetary and Space Scienc

The Boundary Conditions of the Heliosphere: Photoionization Models Constrained by Interstellar and In Situ Data

The boundary conditions of the heliosphere are set by the ionization, density and composition of inflowing interstellar matter. Constraining the properties of the Local Interstellar Cloud (LIC) at the heliosphere requires radiative transfer ionization models. We model the background interstellar radiation field using observed stellar FUV and EUV emission and the diffuse soft X-ray background. We also model the emission from the boundary between the LIC and the hot Local Bubble (LB) plasma, assuming that the cloud is evaporating because of thermal conduction. We create a grid of models covering a plausible range of LIC and LB properties, and use the modeled radiation field as input to radiative transfer/thermal equilibrium calculations using the Cloudy code. Data from in situ observations of He^O, pickup ions and anomalous cosmic rays in the heliosphere, and absorption line measurements towards epsilon CMa were used to constrain the input parameters. A restricted range of assumed LIC HI column densities and LB plasma temperatures produce models that match all the observational constraints. The relative weakness of the constraints on N(HI) and T_h contrast with the narrow limits predicted for the H^O and electron density in the LIC at the Sun, n(H^0) = 0.19 - 0.20 cm^-3, and n(e) = 0.07 +/- 0.01 cm^-3. Derived abundances are mostly typical for low density gas, with sub-solar Mg, Si and Fe, possibly subsolar O and N, and S about solar; however C is supersolar. The interstellar gas at the Sun is warm, low density, and partially ionized, with n(H) = 0.23 - 0.27 cm^-3, T = 6300 K, X(H^+) ~ 0.2, and X(He^+) ~ 0.4. These results appear to be robust since acceptable models are found for substantially different input radiation fields. Our results favor low values for the reference solar abundances for the LIC composition.Comment: 14 pages, 4 figures, submitted to Astronomy & Astrophysics together with papers from the International Space Sciences Institute workshop on Interstellar Hydrogen in the Heliospher

Calcium/calmodulin-dependent kinases can regulate the TSH expression in the rat pituitary.

PURPOSE: The endocrine secretion of TSH is a finely orchestrated process controlled by the thyrotropin-releasing hormone (TRH). Its homeostasis and signaling rely on many calcium-binding proteins belonging to the "EF-hand" protein family. The Ca2+/calmodulin (CaM) complex is associated with Ca2+/CaM-dependent kinases (Ca2+/CaMK). We have investigated Ca2+/CaMK expression and regulation in the rat pituitary. METHODS: The expression of CaMKII and CaMKIV in rat anterior pituitary cells was shown by immunohistochemistry. Cultured anterior pituitary cells were stimulated by TRH in the presence and absence of KN93, the pharmacological inhibitor of CaMKII and CaMKIV. Western blotting was then used to measure the expression of these kinases and of the cAMP response element-binding protein (CREB). TSH production was measured by RIA after time-dependent stimulation with TRH. Cells were infected with a lentiviral construct coding for CaMKIV followed by measurement of CREB phosphorylation and TSH. RESULTS: Our study shows that two CaM kinases, CaMKII and CaMKII, are expressed in rat pituitary cells and their phosphorylation in response to TRH occurs at different time points, with CaMKIV being activated earlier than CaMKII. TRH induces CREB phosphorylation through the activity of both CaMKII and CaMKIV. The activation of CREB increases TSH gene expression. CaMKIV induces CREB phosphorylation while its dominant negative and KN93 exert the opposite effects. CONCLUSION: Our data indicate that the expression of Ca2+/CaMK in rat anterior pituitary are correlated to the role of CREB in the genetic regulation of TSH, and that TRH stimulation activates CaMKIV, which in turn phosphorylates CREB. This phosphorylation is linked to the production of thyrotropin

Cathepsin D protects colorectal cancer cells from acetate-induced apoptosis through autophagy-independent degradation of damaged mitochondria

Acetate is a short-chain fatty acid secreted by Propionibacteria from the human intestine, known to induce mitochondrial apoptotic death in colorectal cancer (CRC) cells. We previously established that acetate also induces lysosome membrane permeabilization in CRC cells, associated with release of the lysosomal protease cathepsin D (CatD), which has a well-established role in the mitochondrial apoptotic cascade. Unexpectedly, we showed that CatD has an antiapoptotic role in this process, as pepstatin A (a CatD inhibitor) increased acetate-induced apoptosis. These results mimicked our previous data in the yeast system showing that acetic acid activates a mitochondria-dependent apoptosis process associated with vacuolar membrane permeabilization and release of the vacuolar protease Pep4p, ortholog of mammalian CatD. Indeed, this protease was required for cell survival in a manner dependent on its catalytic activity and for efficient mitochondrial degradation independently of autophagy. In this study, we therefore assessed the role of CatD in acetate-induced mitochondrial alterations. We found that, similar to acetic acid in yeast, acetate-induced apoptosis is not associated with autophagy induction in CRC cells. Moreover, inhibition of CatD with small interfering RNA or pepstatin A enhanced apoptosis associated with higher mitochondrial dysfunction and increased mitochondrial mass. This effect seems to be specific, as inhibition of CatB and CatL with E-64d had no effect, nor were these proteases significantly released to the cytosol during acetate-induced apoptosis. Using yeast cells, we further show that the role of Pep4p in mitochondrial degradation depends on its protease activity and is complemented by CatD, indicating that this mechanism is conserved. In summary, the clues provided by the yeast model unveiled a novel CatD function in the degradation of damaged mitochondria when autophagy is impaired, which protects CRC cells from acetate-induced apoptosis. CatD inhibitors could therefore enhance acetate-mediated cancer cell death, presenting a novel strategy for prevention or therapy of CRC.FEDER through POFC – COMPETE and by Fundação para a Ciência e Tecnologia through projects PEst-OE/BIA/UI4050/2014 and FCT ANR/BEX-BCM/0175/201

A Modeling Analysis of Wastewater Heat Recovery Effects on Wastewater Treatment Plant Nitrification

A global shift towards renewable energy production, driven primarily by the challenges posed by climate change, is currently underway. In this context, the utilization of heat recovery from municipal wastewater emerges as a promising green technology. Notably, the advantage of implementing energy recovery in sewers, as opposed to wastewater treatment plants (WWTPs), lies in the higher temperature of the wastewater and its proximity to potential heat users. Despite these benefits, concerns arise regarding the potential adverse effects on biological wastewater treatment processes downstream of the heat recovery section, particularly during colder seasons. This paper seeks to assess the impact of a heat recovery system along the sewer network on the efficiency of biological wastewater treatment processes. The methodology involves a modeling analysis of a real sewage network in Italy. Under typical northern Italy climate conditions, the results demonstrate the feasibility of heat recovery in sewers for WWTPs designed with a sludge residence time under aerobic conditions (SRTaer) greater than 13 days. In such cases, the nitrification process remains relatively unaffected. However, for lower SRTaer values, a case-specific feasibility assessment is recommended to evaluate the overall process efficiency comprehensively

Improving training condition assessment in endurance cyclists : Effects of ganoderma lucidum and ophiocordyceps sinensis dietary supplementation

The main reasons for taking daily dietary supplements are to maintain good health, to improve homeostasis, and to create conditions for reducing the risk of disease. Due to growing market demand, the search for effective, nontoxic, natural compounds with antioxidant and ergogenic properties has increasingly become a matter of interest. This paper describes how a specific combination of fungal supplements can help improve the performance of endurance athletes. We report the effects of a brief 3-month trial of two fungal supplements, Ganoderma lucidum and Cordyceps sinensis (3 capsules of O. sinensis and 2 capsules of G. lucidum per day), in 7 healthy male volunteers, aged between 30 and 40 years, who are all amateur cyclists that participate in "Gran Fondo" cycling races. This trial investigated the effects of fungal supplements on the level of physical fitness of the athletes by monitoring and comparing the following biomarkers just before and after physical exertion: the testosterone/cortisol ratio in the saliva and oxidative stress (DPPH free radical scavenging activity). A decrease of more than 30% in the testosterone/cortisol ratio after race compared to before race was considered as a risk factor for nonfunctional overreaching (NFO) or the overtraining syndrome (OTS). The results show that, after 3 months of supplementation, the testosterone/cortisol ratio changed in a statistically significant manner, thereby protecting the athletes from NFO and OTS. Antioxidant activity was measured by quantifying the scavenging ability of the human serum on the synthetic free radical DPPH. After 3 months of fungal supplementation, the data demonstrate an increased scavenger capacity of free radicals in the athletes' serum after the race, thereby protecting the athletes from oxidative stress

Using spectral diversity and heterogeneity measures to map habitat mosaics: An example from the Classical Karst

Questions: Can we map complex habitat mosaics from remote-­sensing data? In doing this, are measures of spectral heterogeneity useful to improve image classification performance? Which measures are the most important? How can multitemporal data be integrated in a robust framework? Location: Classical Karst (NE Italy). Methods: First, a habitat map was produced from field surveys. Then, a collection of 12 monthly Sentinel-­2 images was retrieved. Vegetation and spectral heterogeneity (SH) indices were computed and aggregated in four combinations: (1) monthly layers of vegetation and SH indices; (2) seasonal layers of vegetation and SH indices; (3) yearly layers of SH indices computed across the months; and (4) yearly layers of SH indices computed across the seasons. For each combination, a Random Forest clas- sification was performed, first with the complete set of input layers and then with a subset obtained by recursive feature elimination. Training and validation points were independently extracted from field data. Results: The maximum overall accuracy (0.72) was achieved by using seasonally ag- gregated vegetation and SH indices, after the number of vegetation types was re- duced by aggregation from 26 to 11. The use of SH measures significantly increased the overall accuracy of the classification. The spectral β-­diversity was the most im- portant variable in most cases, while the spectral α-­diversity and Rao's Q had a low relative importance, possibly because some habitat patches were small compared to the window used to compute the indices. Conclusions: The results are promising and suggest that image classification frame- works could benefit from the inclusion of SH measures, rarely included before. Habitat mapping in complex landscapes can thus be improved in a cost-­and time-­effective way, suitable for monitoring applications

Origin and Evolution of Saturn's Ring System

The origin and long-term evolution of Saturn's rings is still an unsolved problem in modern planetary science. In this chapter we review the current state of our knowledge on this long-standing question for the main rings (A, Cassini Division, B, C), the F Ring, and the diffuse rings (E and G). During the Voyager era, models of evolutionary processes affecting the rings on long time scales (erosion, viscous spreading, accretion, ballistic transport, etc.) had suggested that Saturn's rings are not older than 100 My. In addition, Saturn's large system of diffuse rings has been thought to be the result of material loss from one or more of Saturn's satellites. In the Cassini era, high spatial and spectral resolution data have allowed progress to be made on some of these questions. Discoveries such as the ''propellers'' in the A ring, the shape of ring-embedded moonlets, the clumps in the F Ring, and Enceladus' plume provide new constraints on evolutionary processes in Saturn's rings. At the same time, advances in numerical simulations over the last 20 years have opened the way to realistic models of the rings's fine scale structure, and progress in our understanding of the formation of the Solar System provides a better-defined historical context in which to understand ring formation. All these elements have important implications for the origin and long-term evolution of Saturn's rings. They strengthen the idea that Saturn's rings are very dynamical and rapidly evolving, while new arguments suggest that the rings could be older than previously believed, provided that they are regularly renewed. Key evolutionary processes, timescales and possible scenarios for the rings's origin are reviewed in the light of tComment: Chapter 17 of the book ''Saturn After Cassini-Huygens'' Saturn from Cassini-Huygens, Dougherty, M.K.; Esposito, L.W.; Krimigis, S.M. (Ed.) (2009) 537-57