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To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC) and to evaluate in vitro their mechanism of action in sunitinib resistance.We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41). The most relevant differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenotypes selected from an independent cohort (n = 101). In vitro experiments were conducted to study the role of miR-942 in sunitinib resistance.TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p = 0.0074). High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line. MiR-942 overexpression in Caki-2 up-regulates MMP-9 and VEGF secretion which, in turn, promote HBMEC endothelial migration and sunitinib resistance.We identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity or resistance to sunitinib. MiR-942 was the best predictor of efficacy. We describe a novel paracrine mechanism through which high miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance. Our results support further validation of these miRNA in clinical confirmatory studies.

This review presents challenges and recommendations on different aspects related to the management of patients with localized muscle-invasive bladder cancer (MIBC), which were discussed by a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group within the framework of the Genitourinary Alliance project (12GU). It is necessary to clearly define which patients are candidates for radical cystectomy and which are candidates for undergoing bladder-sparing procedures. In older patients, it is necessary to include a geriatric assessment and evaluation of comorbidities. The pathological report should include a classification of the histopathological variant of MIBC, particularly the identification of subtypes with prognostic, molecular and therapeutic implications. Improvement of clinical staging, better definition of prognostic groups based on molecular subtypes, and identification of biomarkers potentially associated with maximum benefit from neoadjuvant chemotherapy are areas for further research. A current challenge in the management of MIBC is improving the selection of patients likely to be candidates for immunotherapy with checkpoint inhibitors in the neoadjuvant setting. Optimization of FDG-PET/CT reliability in staging of MIBC and the selection of patients is necessary, as well as the design of prospective studies aimed to compare the value of different imaging techniques in parallel.

Abstract The aim of this work was to provide further confirmation of the possible use of non-linear ultrasonic techniques for detecting the cracking due to corrosion of steel reinforcements in concrete. To this end accelerated steel corrosion tests have been conducted on model reinforced cement mortar specimens, while monitoring the appearance and width evolution of visible surface cracks, and performing non-linear ultrasonic measurements based on the phenomena of harmonic distortion and intermodulation. A new parameter, based on the difference between the amplitude of the fundamental frequency and the sum of the amplitudes of all the first-order and second-order intermodulation products, has been proposed in this work. The results confirm that the appearance of visible surface micro-cracks are preceded and accompanied by the observation of strong non-linear features in the received signal. Furthermore, the new parameter proposed in this work is as efficient as the relative non-linearity parameters, classically used in harmonic distortion non-linear ultrasonic studies, for detecting the non-linear features associated with the critical events of the cracking of cement mortar due to embedded steel corrosion. A hypothesis has been developed considering the possible effect of the filling of the void space by liquid containing rust products after the formation of new cracks or the enlargement of its width. This filling process, which might be particularly enhanced by net convective transport of liquid, would explain the evolution of the values of all the parameters used for putting in evidence the non-linear elastic features after the critical events of the cracking process.

Objective: Our aim was to provide practical recommendations on the management of patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after docetaxel plus androgen-deprivation therapy (ADT) or abiraterone plus ADT. Methods: Systematic literature review (SLR), nominal group meeting, and Delphi process. A panel of 12 experts was established who defined the scope, users, and sections of the document. We performed an SLR in order to assess the efficacy and safety of available drugs in patients with mCRPC. Abstracts from the American Society of Oncology and European Society for Medical Oncology meetings were also examined. The results were discussed during an expert meeting in which 14 recommendations were generated. The level of agreement with the recommendations was also tested by 13 additional experts following the Delphi process. Recommendations were voted by means of scores ranging from 0 (total disagreement) to 10 (total agreement). We defined agreement when at least 70% of the experts voted ⩾7. Next, we assigned a level of evidence and grade to the recommendation using the Oxford Centre for Evidence-based Medicine Levels of Evidence, following which the final document was drafted. Results: The literature search did not find any articles meeting the inclusion criteria. Finally, 13 out of 14 recommendations were accepted after two Delphi rounds (two were modified after the first round). They pertain to general and individual case-based treatment recommendations. Conclusions: In mCRPC patients who have progressed after docetaxel or abiraterone plus ADT in the metastatic hormone-sensitive prostate cancer setting, these recommendations may support treatment decision-making, due to the lack of evidence or other globally accepted sequencing algorithms.

Currently, reduction of environmental effects of the cement industry is an issue of global interest and one of the alternatives is to replace clinker with additions such as volcanic powder. The purpose of this work is to study the influence of up to 400 hardening days of volcanic powder, obtained from the last eruption of the Calbuco volcano (Chile), on the pore structure, mechanical performance, and durability-related properties of mortars which incorporate up to 20% volcanic powder as a substitution for clinker. In addition, an evaluation of greenhouse gases emissions was performed in order to quantify the possible environmental benefits of incorporating the volcanic powder in the mortars. The results obtained indicated that mortars with contents of 10% and 20% of volcanic powder had adequate service properties and improved all durability-related properties overall as compared with those noted for ordinary Portland cement. Additionally, the use of up to 20% volcanic powder makes it possible to reduce the CO2 emissions of mortars by almost 20%, demonstrating the advantages of incorporating this addition in mortars.

An electrochemical model is presented to calculate the rebar shape time-evolution in reinforced mortar specimens during forced corrosion tests. This provides a more realistic description than the usually used geometric models. The current distribution along the rebar perimeter is calculated by using Finite Element Method (FEM) to solve Laplace equation. Then, Faraday’s law is used to relate current distribution to rebar volume increase due to corrosion products creation. The shape of the rebar section is obtained as a function of corrosion time.

Recently, there has been a great effort to incorporate industrial waste into cement-based materials to reach a more sustainable cement industry. In this regard, the Bayer process of obtaining alumina from bauxite generates huge amounts of waste called red mud. Few research articles have pointed out the possibility that red mud has pozzolanic activity. In view of that, the objective of this research is to analyse the short-term effects in the pore structure, mechanical performance and durability of mortars which incorporate up to 20% of red mud as a clinker replacement. As a reference, ordinary Portland cement and fly ash Portland cement mortars were also studied. The microstructure was characterised through mercury intrusion porosimetry and non-destructive impedance spectroscopy, which has not previously been used for studying the pore network evolution of red mud cement-based materials. The possible pozzolanic activity of red mud has been checked using differential scanning calorimetry. The non-steady state chloride migration coefficient and the mechanical properties were studied too. According to the results obtained, the addition of red mud entailed a greater microstructure refinement of the mortar, did not worsen the resistance against chloride ingress and reduced the compressive strength compared to control binders.

In this work, non-linear ultrasonic wave techniques have been used to detect the onset of micro-cracking due to steel corrosion in model reinforced concrete elements. The specimens were of prismatic shape with a single steel rebar. The corrosion was forced by admixing an appropriate amount of sodium chloride at the moment of preparing the concrete mix, and by the application of an electric field, using a constant current density power source, and making the steel rebar work as the anode, and an external counter-electrode as the cathode. The preliminary results indicate that the onset of cracking seems to be accompanied by the appearance of higher-harmonic generation at the output signal (harmonic distortion), when the system is excited by the means of an ultrasound wave with a burst central frequency. Other phenomena related to the micro-cracks induced by corrosion, such is the parametric generation with respect to the fundamental amplitude, have not been observed until now.

Nowadays, cement manufacture is one of the most polluting worldwide industrial sectors. In order to reduce its CO2 emissions, the clinker replacement by ground granulated blast–furnace slag and fly ash is becoming increasingly common. Both additions are well-studied when the hardening conditions of cementitious materials are optimum. Therefore, the main objective of this research was to study the short-term effects of exposure, to both laboratory simulated and real in situ Mediterranean climate environments, on the microstructure and durability-related properties of mortars made using commercial slag and fly ash cements, as well as ordinary Portland cement. The real in situ condition consisted of placing the samples at approximately 100 m away from the Mediterranean Sea. The microstructure was analysed using mercury intrusion porosimetry. The effective porosity, the capillary suction coefficient and the non-steady state chloride migration coefficient were also studied. In view of the results obtained, the non-optimum laboratory simulated Mediterranean environment was a good approach to the real in situ one. Finally, mortars prepared using sustainable cements with slag and fly ash exposed to both Mediterranean climate environments, showed adequate service properties in the short-term (90 days), similar to or even better than those in mortars made with ordinary Portland cement.

Today, the characterisation of the microstructure of cement-based materials using non-destructive techniques has become an important topic of study, and among them, the impedance spectroscopy has recently experienced great progress. In this research, mortars with two different contents of fly ash were exposed to four different constant temperature and relative humidity environments during a 180-day period. The evolution of their microstructure was studied using impedance spectroscopy, whose results were contrasted with mercury intrusion porosimetry. The hardening environment has an influence on the microstructure of fly ash cement mortars. On one hand, the impedance resistances R1 and R2 are more influenced by the drying of the materials than by microstructure development, so they are not suitable for following the evolution of the porous network under non-optimum conditions. On the other hand, the impedance spectroscopy capacitances C1 and C2 allow studying the microstructure development of fly ash cement mortars exposed to those conditions, and their results are in accordance with mercury intrusion porosimetry ones. Finally, it has been observed that the combined analysis of the abovementioned capacitances could be very useful for studying shrinkage processes in cement-based materials kept in low relative humidity environments.

At present, sustainability is of major importance in the cement industry, and the use of additions such as silica fume as clinker replacement contributes towards that goal. Special foundations, and particularly micropiles, are one of the most suitable areas for the use of sustainable cements. The aim of this research is to analyse the effects in the very long-term (for 600 days) produced by sulphate attack in the microstructure of grouts for micropiles in which OPC (ordinary Portland cement) has been replaced by 5% and 10% silica fume. This line of study is building on a previous work, where these effects were studied in slag and fly ash grouts. Grouts made using a commercial sulphate-resisting Portland cement were also studied. The non-destructive impedance spectroscopy technique, mercury intrusion porosimetry, and Wenner resistivity testing were used. Mass variation and the compressive strength have also been analysed. Apparently, impedance spectroscopy is the most suitable technique for studying sulphate attack development. According to the results obtained, grouts for micropiles with a content of silica fume up to 10% and exposed to an aggressive sulphate medium, have a similar or even better behaviour in the very long-term, compared to grouts prepared using sulphate-resisting Portland cement.

At present, one of the most suitable ways to get a more sustainable cement industry is to reduce the CO2 emissions generated during cement production. In order to reach that goal, the use of ground granulated blast-furnace slag as clinker replacement is becoming increasingly popular. Although the effects of this addition in the properties of cementitious materials are influenced by their hardening conditions, there are not too many experimental studies in which slag concretes have been exposed to real in situ environments. Then, the main objective of this research is to study the short-term effects of exposure to real Mediterranean climate environment of an urban site, where the action of airborne chlorides from sea water and the presence of CO2 are combined, in the microstructure and service properties of a commercial slag cement concrete, compared to ordinary Portland cement (OPC). The microstructure was studied with mercury intrusion porosimetry. The effective porosity, capillary suction coefficient, chloride migration coefficient, carbonation front depth, and compressive strength were also analyzed. Considering the results obtained, slag concretes exposed to a real in situ Mediterranean climate environment show good service properties in the short-term (180 days), in comparison with OPC.

Nowadays, one of the most popular ways to get a more sustainable cement industry is using additions as cement replacement. However, there are many civil engineering applications in which the use of sustainable cements is not extended yet, such as special foundations, and particularly micropiles, even though the standards do not restrict the cement type to use. These elements are frequently exposed to the sulphates present in soils. The purpose of this research is to study the effects in the very long-term (until 600 days) of sulphate attack in the microstructure of micropiles grouts, prepared with ordinary Portland cement, fly ash and slag commercial cements, continuing a previous work, in which these effects were studied in the short-term. The microstructure changes have been analysed with the non-destructive impedance spectroscopy technique, mercury intrusion porosimetry and the “Wenner” resistivity test. The mass variation and the compressive strength have also been studied. The impedance spectroscopy has been the most sensitive technique for following the sulphate attack process. Considering the results obtained, micropiles grouts with slag and fly ash, exposed to an aggressive medium with high content of sulphates, have shown good behaviour in the very long-term (600 days) compared to grouts made with OPC.

Purpose: To describe estradiol (E2), estrone (E1), and estrone sulfate (E1S) levels during the first year of monthly triptorelin plus exemestane or tamoxifen and to assess possible suboptimal suppression while receiving exemestane plus triptorelin., Patients and Methods: Premenopausal patients with early breast cancer on the Suppression of Ovarian Function Trial who selected triptorelin as the ovarian suppression method and were randomly assigned to exemestane plus triptorelin or tamoxifen plus triptorelin were enrolled until the target population of 120 patients was reached. Blood sampling time points were 0, 3, 6, 12, 18, 24, 36, and 48 months. Serum estrogens were measured with a highly sensitive and specific assay. This preplanned 12-month analysis evaluated E2, E1, E1S, follicle-stimulating hormone, and luteinizing hormone levels in all patients and the proportion of patients with E2 levels greater than 2.72 pg/mL at any time point during treatment with exemestane plus triptorelin., Results: One hundred sixteen patients (exemestane, n = 86; tamoxifen, n = 30; median age, 44 years; median E2, 51 pg/mL; 55% prior chemotherapy) started triptorelin and had one or more samples drawn. With exemestane plus triptorelin, median reductions from baseline E2, E1, and E1S levels were consistently ≥ 95%, resulting in significantly lower levels than with tamoxifen plus triptorelin at all time points. Among patients on exemestane plus triptorelin, 25%, 24%, and 17% had an E2 level greater than 2.72 pg/mL at 3, 6, and 12 months, respectively. Baseline factors related to on-treatment E2 level greater than 2.72 pg/mL were no prior chemotherapy (P = .06), higher body mass index (P = .05), and lower follicle-stimulating hormone and luteinizing hormone (each P < .01)., Conclusion: During the first year, most patients on exemestane plus triptorelin had E2 levels below the defined threshold of 2.72 pg/mL, consistent with levels reported in postmenopausal patients on aromatase inhibitors, but at each time point, at least 17% of patients had levels greater than the threshold., (© 2016 by American Society of Clinical Oncology.)