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Background: Immune checkpoint inhibitors are a standard therapy in metastatic urothelial carcinoma (UC). Long-term follow-up is necessary to confirm durability of response and identify further safety concerns. Patients and methods: In KEYNOTE-045, patients with metastatic UC that progressed on platinum-containing chemotherapy were randomly assigned 1:1 to receive pembrolizumab or investigator's choice of paclitaxel, docetaxel, or vinflunine. Primary endpoints were progression-free survival per RECIST version 1.1 by blinded independent central review (BICR) and overall survival. In KEYNOTE-052, cisplatin-ineligible patients with metastatic UC received first-line pembrolizumab. The primary endpoint was objective response rate per RECIST version 1.1 by BICR. Results: A total of 542 patients (pembrolizumab, n = 270; chemotherapy, n = 272) were randomly assigned in KEYNOTE-045. The median follow-up was 62.9 months (range 58.6-70.9 months; data cut-off 1 October 2020). At 48 months, overall survival rates were 16.7% for pembrolizumab and 10.1% for chemotherapy; progression-free survival rates were 9.5% and 2.7%, respectively. The median duration of response (DOR) was 29.7 months (range 1.6+ to 60.5+ months) for pembrolizumab and 4.4 months (range 1.4+ to 63.1+ months) for chemotherapy; 36-month DOR rates were 44.4% and 28.3%, respectively. A total of 370 patients were enrolled in KEYNOTE-052. The median follow-up was 56.3 months (range 51.2-65.3 months; data cut-off 26 September 2020). The confirmed objective response rate was 28.9% (95% confidence interval 24.3-33.8), and the median DOR was 33.4 months (range 1.4+ to 60.7+ months); the 36-month DOR rate was 44.8%. Most treatment-related adverse events for pembrolizumab in either study were grade 1 or 2 and manageable, which is consistent with prior reports. Conclusion: With ∼5 years of follow-up, pembrolizumab monotherapy continued to demonstrate durable efficacy with no new safety signals in patients with platinum-resistant metastatic UC and as first-line therapy in cisplatin-ineligible patients. Clinical trial registry and ID: With ClinicalTrials.gov NCT02256436 (KEYNOTE-045); https://clinicaltrials.gov/ct2/show/NCT02256436 and NCT02335424 (KEYNOTE-052); https://clinicaltrials.gov/ct2/show/NCT02335424

Cathodic protection is a method to protect reinforced concrete structures located in saline environments against corrosion effect produced by Cl− penetration. But there are significant differences among these aggressive environments. The aim of this article is to show how different ways of saline contamination can affect the efficiency of cathodic protection. For this research, a series of laboratory specimens representing structural elements were subjected to two versions of cathodic protection (cathodic protection strictly speaking, and cathodic prevention), while two different ways of saline contamination were applied (permanent immersion in a NaCl solution and periodic pouring of discrete amounts of a NaCl solution in atmospheric exposure). Depending on the saline environment, differences in the efficiency of cathodic protection were detected. Results can be useful to determine the specific features of the cathodic protection to be applied in each case, taking into account both the initial Cl− content of the structural element and the particular saline environment where it is located. This research was funded by the Spanish Ministerio de Economía y Competitividad (and formerly by the Spanish Ministerio de Ciencia e Innovación) and European Regional Development Fund (ERDF) through projects BIA2010-20548 and MAT2009-10866, respectively, and also through the project PROMETEO/2013/035 of Generalitat Valenciana (Spain).

In this work, the durability performances of mortars made with an ordinary Portland cement and a slag cement, were tested. These mortars were exposed to four different constant temperature and relative humidity during 365 days. The measured properties of both cement types are affected by the environment, but the durability of slag cement mortars is more influenced by temperature and the durability of OPC mortars is more influenced by the relative humidity. The obtained results show that the slag cement mortars hardened under non-optimal environmental conditions have good durability at any hardening age, even better than Portland cement.

One of the most important problems of reinforced steel concrete in marine environments is the corrosion of the reinforcing bars. Most of the times, this corrosion is a consequence of the local destruction of the passive layer formed on the surface of the embedded steel, due to the arrival of chlorides present in the environment. Many efforts have been made to determine the chloride diffusion coefficient in concrete structures, both using natural diffusion methods, and accelerated migration methods. This coefficient determines the velocity of ingress of chlorides, and as a consequence the life time of the structures. In this work it is presented the possibility of using the technique of impedance spectroscopy, that is, very simple to use and requires no chemical or conductivity measurement, to determine the value of the non-steady-state diffusion coefficient. This technique, together with the equivalent circuits proposed for the interpretation of the measurements, allows the determination of the chloride saturation of a concrete or mortar sample. Pores of the material that are initially filled with water have high resistivity, and as the chlorides penetrate into the sample the value of the resistivity decreases. This diminution can be determined in situ, and permits the calculation of the diffusion coefficient saving experimental time and efforts. The results have been obtained both with concrete and mortar samples, and using different cement types.

The results of this research show the viability of using a conductive cement paste anode for the electrochemical extraction of chlorides from reinforced concrete with an efficiency similar to that obtained with a classic Ti–RuO2 anode. The obtained efficiencies are within the typical range of values of overall efficiencies found for such treatments. The thickness of the conductive cement paste anode has a great influence on the capacity of the anode to retain an important part of the extracted chlorides after finishing the electrochemical treatments.

The forced migration test has been used during the last decades as an accelerated and useful method for determining the resistance of concrete to chloride ingress. Furthermore it allows to determine transport parameters of chloride ions through porous materials. The application of electric fields seems to introduce variations in the microstructure of concrete. In this work these variations have been studied using the impedance spectroscopy technique in the high frequency region (1 kHz–1 MHz). The results show that the dielectric response of concrete is also strongly modified during the migration experiments. The variations of the dielectric parameters during the migration tests can be explained in terms of modifications of the microstructure of concrete. The observed modifications are in good agreement with the results of mercury porosimetry analysis.

In this work, it is demonstrated that it is possible to eliminate the filtration step in the determination of the acid-soluble chloride content of cement and concrete by potentiometric titration, irrespective of the method used for detecting the end-point of the titration. Extensive analytical results are presented corresponding to several types of cement and to a broad range of chloride concentrations in concrete. Some requirements to avoid errors in such analytical determinations are discussed.

Purpose: We evaluate the safety and efficacy of conservative elective treatment of upper urinary tract tumors, and determine predictive factors for recurrence and progression to optimize indications of this type of treatment.Materials and Methods: Since 1984 we have performed a prospective study of conservative treatment of single, low grade and stage, less than 3 cm. upper tract tumors. The study includes 54 patients with a normal contralateral kidney who had been followed for more than 36 months. Open conservative surgery was performed in 31 cases and endourological surgery in 23. Minimum followup was 36 months, maximum 210 and mean 84.8. Univariate and multivariate analyses of recurrence and progression were performed in relation to age, sex, association with a bladder tumor, bladder tumor stage and grade, sequence of bladder tumor in relation to upper urinary tract tumor, number of previous bladder tumor recurrences, association with bladder carcinoma in situ, upper urinary tract tumor grade, ...

A test method is proposed for measuring chloride diffusion coefficients through nonsaturated concrete specimens with controlled water contents. The experimental setup used allows one to supply an initial limited amount of Cl − to the tested concrete surface. The procedure consists of submitting the surface of concrete specimens to interaction with the products of combustion of PVC, which contain mainly gaseous hydrogen chloride. This interaction yields a limited Cl − contamination of the concrete surface. After returning the specimens to their controlled humidity exposure conditions, the kinetics of Cl − transport from the surface inwards may be studied. The experimental Cl − concentration profiles determined at selected time intervals have been adjusted to a diffusion model of “instantaneous plane source,” which takes into account the particular initial and boundary conditions of the experimental procedure, for obtaining the corresponding diffusion coefficients.

When obtaining dust concrete samples by dry drilling to determine chloride content profiles, the common conical shape of the bit tip induces some problems for assigning the analyzed Cl− content of each sample to a fixed depth from surface, (which is necessary for applying Cl− transport models): the amount of concrete removed is not the same throughout the length of a single drilling step, and concrete coming from depths lower than the nominal drilling step is also obtained. It is proposed that each Cl− concentration in the profile should be assigned to the gravity centre of the solid sample really removed in each drilling step, instead of assigning it to the centre of the nominal drilling step. A simple method for calculating the gravity centre of each sample obtained by dry drilling, has been developed. The calculated values of Cl− diffusion coefficients from a Cl− content profile may be appreciably lower if the centres of gravity of the samples, instead of the centres of the nominal drilling steps, are used for the calculations.

A potentiometric titration procedure that makes use of Gran’s method for end-point detection has been developed to analyze acid-soluble chloride in cement, mortar, and concrete, eliminating the filtration steps performed in habitual laboratory reference methods. The accuracy and reliability of the proposed analytical technique has been checked against a standard method, such as Volhard’s, by analyzing duplicate samples of cements, mortars, and concretes with varied chloride contents.

Chloride contamination of concrete by interaction with PVC combustion gases has been studied in a small-scale testing chamber, which allows simulating the conditions probably prevailing in PVC fires of different magnitude through variation of the quotient between mass of burnt PVC and exposed concrete surface (PVC/S). In all cases, a steep gradient of chloride concentration with depth is found after the fire: most chloride is detected in the outermost layer at depths below 5 mm. Surface chloride contents (within 5 mm) for prestressed and reinforced concretes, tested with a high (PVC/S) ratio, are as high as 2.5 and 5% by weight of cement, respectively. Chloride concentrations in concrete near the steels are below the corrosion thresholds after the fire, but they can rise by diffusion to values able to induce rebar corrosion, especially if concrete is exposed to a humid atmosphere.

Today, the use of micropiles for different applications has become very common. In Spain, the cement grouts for micropiles are prepared using ordinary Portland cement and w:c ratio 0.5, although the micropiles standards do not restrict the cement type to use, provided that it reaches a certain compressive strength. In this study, the influence of using slag cement on the microstructure and durability related properties of cement grouts for micropiles have been studied until 90 hardening days, compared to an ordinary Portland cement. Finally, slag cement grouts showed good service properties, better than ordinary Portland cement ones. This work has been financially supported by the Ministerio de Ciencia e Innovación of Spain though projects BIA2010-20548 and BIA2011-25721. J.M. Ortega is indebted to the Ministerio de Educación of Spain for a fellowship of the "Formación Personal Investigador (FPI)" programme (reference BES-2008-002650).

Carbonation of concrete by atmospheric CO 2 may lead to breakdown of the passivating layer of the steel reinforcements, leading to catastrophic corrosion, if the pH of the electrolyte in the concrete pores decreases below 8. The nature of this carbonation process has been studied by means of potential-modulated reflectance (PMR) spectroscopy, following the changes in the PMR spectrum of air-passivated iron in 1M NaOH produced by sparging the electrolyte with a CO 2 + air mixture. Decreasing the pH from 8.02 to 7.69 produced the disappearance of the Fe 2 O 3 PMR signal and nearly a doubling of the PMR maximum of FeOOH, pointing to a hydration of Fe 2 O 3 to FeOOH preceding the breakdown of the passivating layer. A further decrease of only 0.07 pH units, down to pH 7.62, effected an increase of the corrosion rate of nearly two orders of magnitude and the disappearance of the PMR spectrum of the passivating layer, this being the first spectroscopic proof that depassivation by carbonation is due to a complete electrochemical dissolution of the passivating layer.

The measurement of the free chloride concentration in the pore solution of cement paste or concrete is of interest for assessing the probability of corrosion of the steel reinforcements embedded in concrete. This determination is performed through leaching or pore-pressing methods or through embedded potentiometric sensors into the hardened cementitious material. The potentiometric determination of chloride in cement paste pore solutions is limited by hydroxide ion interference, due to the high alkalinity of such media. The potentiometric selectivity coefficients, k Cl - , OH - , are determined for a chloride ionic selective electrode in alkaline solutions simulating the electrolyte present within the pore network of cement paste and concrete. This is done using a fixed interference methodology, with least-squares non-linear curve fitting for obtaining the selectivity coefficients together with other relevant electrode parameters. The limit of detection of the Cl− ISE, due to OH− interference, varies with pH. For the pore solution corresponding to an ordinary Portland cement paste or concrete, this limit can be set between 3 × 10–3 m, and 7 × 10–3 m, i.e., approximately below a chloride concentration value of 1 × 10–2 molal. Taking into account these limits of detection the free Cl− concentrations able to depassivate the steel, can be adequately determined by potentiometric measurements with calibrated ISEs in the expressed pore solutions of Portland cement concretes, without significant influence of OH− interference. Nevertheless, this effect can prevent the adequate measurement of low free Cl− concentrations, below the corresponding limit of detection value.

The use of impedance spectroscopy, IS, has become a useful technique for the microstructural characterisation of cement pastes and mortars. The main advantage is that it is non destructive, but in the other hand the interpretation of the results obtained is not straightforward. A model has been proposed that gives microstructural interpretation of the electrical parameters obtainable from the impedance data. Here is presented a validation of that model, using a model material, which allows controlled changes in the electrolyte conductivity to be monitored by IS. The conductivity of pore solution cannot be controlled in cementitious materials, which makes very difficult to differentiate between changes of pore structure and changes in conductivity. The results presented here show good agreement between predictions of the model, and experimental results.

The effect of mechanical loading in concrete structures may cause deformation by creeping. The physical origin of this phenomenon is not well known, but water seems to play an essential role in it. Impedance spectroscopy in the high frequency region can detect water movements towards empty pores, even when the applied load is small. In this paper a system for application of mechanical loading compatible with simultaneous impedance spectroscopy measurements is presented. The effect of several parameters (ageing, water to cement ratio, water content) on cement paste samples’ performance under mechanical loading is analysed through the corresponding impedance spectra.

A test method is proposed for measuring chloride diffusion coefficients through partially saturated concrete specimens with well characterized water contents. It includes an experimental procedure for supplying a limited amount of Cl- to the tested concrete surface, and two mathematical models for processing the experimental Cl- content profiles obtained at selected diffusion times. The use of the more refined model, taking into account the chloride binding by concrete, allows to increase the reliability of the determined diffusion coefficients. For the two tested Portland cement concretes, (water/cement ratios 0.6 and 0.5), the Cl- diffusion coefficient decreases about two orders of magnitude, from 6 · 10- 12 to 2 · 10- 14 m2/s, when the relative humidity of the atmosphere in equilibrium with concrete is lowered from 95% to 54% approximately. © 2007 Elsevier Ltd. All rights reserved., This work has been financially supported by the Ministerio de Ciencia y Tecnología of Spain and by the Fondo Europeo de Desarrollo Regional (FEDER) through project BQU2001-0837-C02-01. We thank also the funding from the Competitive and Sustainable Growth Programme of the European Community through contract G6RD-CT-2002-00855 (Chlortest project).

HER-2/neu and p53 expression, conventional clinical and pathologic prognostic factors, were evaluated in a retrospective series of 283 node-positive breast cancer patients. Overexpression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. Twenty one percent were HER-2/neu positive and 40% p53 positive. HER-2/neu expression was related to axillary lymph node metastasis (P=0.014), inflammatory infiltrates (P=0.004), and the absence of oestrogen (ER) (P=0.0026) and progesterone (P=0.01) receptors (PR). p53 expression was related to lymph node involvement (P=0.03), necrosis (P=0.036), absence of ER (P=0.028) and PR (P=0.065). p53 was not associated with outcome. HER-2/neu was an unfavourable prognostic factor for disease-free (DFS) (P=0.05) and overall survival (OS) (P=0.02) in univariate analysis. Multivariate analysis showed that the number of involved axillary nodes (P

Concrete pore solutions are concentrated electrolytes in which the activity of the chemical species must be calculated properly to determine the equilibrium state of such solutions. In this work, the chloride-ion activity coefficients in synthetic concrete pore solutions have been obtained potentiometrically, using different calibrated Cl− ion-selective electrodes (ISEs); also, a discussion about the performance of the different Cl− ISEs in alkaline media is presented. Experimental results are compared with the calculated results, using Pitzer's specific ionic-interaction model, and good agreement is observed between them.

The study of chemical and electrochemical equilibria between concrete or embedded steel and ionic species in concrete's pore solution requires the knowledge of ion activities (free concentrations in solution). Recently, a method has been developed for measuring chloride-ion (Cl−) activities in simplified synthetic concrete pore solutions using calibrated Cl− selective electrodes. Cl− activities also have been calculated using Pitzer's specific ionic-interaction model. In this work, we have applied both of these methods, experimental and theoretical, for obtaining Cl− activities in solutions obtained using the technique of “pore pressing,” which has been applied to cement pastes with varied admixed Cl− concentrations. A reasonably good agreement has been found between experimental and theoretical results, but the presence of hydroxide ions in these highly alkaline electrolytes interferes with the measurements at low Cl− concentrations.