Complete Generalization of the Equations for the Stress-Strain Curves of Concrete under Uniaxial Compression.

The existence of more than thirty stress-strain equations, including those proposed by the government regulations in many countries, seems to indicate that additional, unifying, and at the same time generalizing research is necessary for this subject. Many expressions can be found to set or determine the initial modulus of elasticity of concrete, i.e., the modulus of elasticity of concrete when no load has been applied to it. This work proposes a complete generalization of the equations based on scalar damage models, applicable to all types of concrete tested under uniaxial compression with any constant rate of stress or strain, although in no case can it be considered a constitutive model. We prefer to discuss an equation that models the shape of the stress-strain curve. Thus, the shape of this curve is studied here in the same way a forensic scientist would, which is why we could see this work as an autopsy carried out on the test specimen through the trace left in the plane σ-ε by the straining process up until its inevitable outcome. That is to say, we believe in a purely phenomenological approach. The results are compared with the data obtained experimentally by analyzing test specimens made using various mixed portions of cement, water, and aggregates.

High-dose radiotherapy and risk-adapted androgen deprivation in localised prostate cancer (DART 01/05): 10-year results of a phase 3 randomised, controlled trial.

BACKGROUND: The optimal duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains controversial. The DART 01/05 trial was designed to determine whether long-term androgen deprivation is superior to short-term androgen deprivation when combined with high-dose radiotherapy. The 5-year results showed that 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy significantly improved biochemical control, metastasis, and overall survival, especially in patients with high-risk disease. In this report, we present the 10-year final results of the trial. METHODS: This open-label, phase 3, randomised, controlled trial was done in ten hospitals in Spain. The eligibility criteria included patients aged 18 years or older with histologically confirmed T1c to T3, N0, and M0 adenocarcinoma of the prostate, according to the 2002 classification of the American Joint Committee on Cancer, with intermediate-risk and high-risk factors, prostate-specific antigen (PSA) less than 100 ng/mL, and a Karnofsky performance score of at least 70%. Patients were randomly assigned (1:1) to receive 4 months of neoadjuvant and concomitant short-term androgen deprivation (STAD) plus high-dose radiotherapy (minimum dose 76 Gy; median dose 78 Gy) or to receive the same treatment followed by 24 months of adjuvant long-term androgen deprivation (LTAD), via a randomisation scheduled generated by Statistical Analysis Software programme (version 9.1) and an interactive web response system. Patients assigned to the STAD group received 4 months of neoadjuvant and concomitant androgen deprivation (oral flutamide 750 mg per day or oral bicalutamide 50 mg per day) with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy was added during the first 2 months of treatment. Patients assigned to LTAD continued with goserelin every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival at 5 years. For this 10-year study we analysed overall survival, metastasis-free survival, biochemical disease-free survival, and cause-specific survival. Analysis was by intention to treat. This trial is closed and is registered at ClinicalTrials.gov (NCT02175212) and in the EU Clinical Trials Register (EudraCT 2005-000417-36). FINDINGS: Between Nov 7, 2005, and Dec 20, 2010, 355 patients were enrolled. One patient in the STAD group withdrew from the trial, hence 354 participants were randomly assigned to STAD (n=177) or LTAD (n=177). The median follow-up was 119·4 months (IQR 100·6-124·3). The 10-year biochemical disease-free survival for LTAD was 70·2% (95% CI 63·1-77·3) and for STAD was 62·3% (54·9-69·7; hazard ratio [HR] 0·84; 95% CI 0·50-1·43; p=0·52). At 10 years, overall survival was 78·4% (72·1-84·8) for LTAD and 73·3% (66·6-80·0) for STAD (HR 0·84; 95% CI 0·55-1·27; p=0·40), and metastasis-free survival was 76·0% (69·4-82·7) for LTAD and 70·9% (64·0-77·8) for STAD (HR 0·90; 95% CI, 0·37-2·19; p=0·81). For the subgroup of high-risk patients, the 10-year biochemical disease-free survival was 67·2% (57·2-77·2) for LTAD and 53·7% (43·3-64·1) for STAD (HR 0·90; 95% CI 0·49-1·64; p=0·73), the 10-year overall survival was 78·5% (69·6-87·3) for LTAD and 67·0% (57·3-76·7) for STAD (HR 0·58; 95% CI 0·33-1·01; p=0·054), and the 10-year metastasis-free survival was 76·6% (95% CI 67·6-85·6) for LTAD and 65·0% (55·1-74·8) for STAD (HR 0·89; 95% CI 0·33-2·43; p=0·82). Only 11 (3%) of 354 patients died from prostate cancer, all of them in the high-risk subgroup (five in the LTAD group and six in the STAD group). 76 (21%) patients died from other causes (mainly second malignancies in 31 [9%] and cardiovascular disease in 21 [6%]). No treatment-related deaths were observed. INTERPRETATION: After an extended 10-year follow-up, we were unable to support the significant benefit of LTAD reported at 5 years. However, the magnitude of the benefit was clinically relevant in high-risk patients. Intermediate-risk patients treated with high-dose radiotherapy do not benefit from LTAD. A biological characterisation with the inclusion of genomic testing is needed in the decision-making process. FUNDING: Grupo de Investigación en Oncología Radioterápica and Sociedad Española de Oncología Radioterápica, the National Health Investigation Fund, and AstraZeneca.

Biogeochemical characterization of surface waters in the Aljustrel mining area (South Portugal).

Aljustrel mining area (South Portugal) is a part of the Iberian Pyrite Belt and encloses six sulfide mineral masses. This mine is classified of high environmental risk due to the large tailings' volume and acid mine drainage (AMD)-affected waters generated by sulfides' oxidation. The use of biological indicators (e.g., diatoms) revealed to be an important tool to address the degree of AMD contamination in waters. Multivariate analysis has been used as a relevant approach for the characterization of AMD processes. Cluster analysis was used to integrate the significant amount and diversity of variables (physicochemical and biological), discriminating the different types of waters, characterized by the high complexity occurring in this region. The distinction of two main marked phenomena was achieved: (1) the circumneutral-Na-Cl water type (sites DA, PF, BX, BF, RO, CB), expressing the geological contributions of the Cenozoic sediments of Sado river basin, with high diatom diversity (predominating brackish diatoms as Entomoneis alata); and (2) the acid-metal-sulfated water type (sites BM, JU, RJ, AA, MR, BE, PC, AF), reflecting both the AMD contamination and the dissolution of minerals (e.g., silicates) from the hosting rocks, potentiated by the extremely low pH. This last group of sites showed lower diatom diversity but with typical diatoms from acid- and metal-contaminated waters (e.g., Pinnularia aljustrelica). In addition to these two water types, this hierarchical classification method also allowed to distinguish individual cases in subclusters, for example, treated dams (DC, DD), with alkaline substances (lime/limestone), that changed the physicochemical dynamics of the contaminated waters.

Negative pH values in an open-air radical environment affected by acid mine drainage. Characterization and proposal of a hydrogeochemical model.

This paper presents the finding of a singular environment polluted by acid mine drainage in the Iberian Pyrite Belt. This situation is regulated by particular conditions, thus the analysed values can be considered as extreme, not only because of the high concentrations of toxic elements, but also due to the extreme low pH, reaching an average negative pH of -1.56, never found before in open-air environments contaminated by acid mine drainage. Concentrations up to 59 g/L of Fe, 2.4 g/L of Al, 740 mg/L of As, 4.3 mg/L of Co, 5.3 mg/L of Ge, 4.8 mg/L of Sb, inter alia, can be found dissolved in these polluted waters. The main aims of the present work are the physicochemical characterization and the toxicity assessment of these radical polluted waters. In addition, a hydrogeochemical model of the system will be proposed, which justifies the extreme pH value and the extraordinarily high concentrations of toxic elements, even for acid mine drainage polluted environments. Extreme acidity and metal and sulphate concentrations in the Radical Environment are due to several processes of different nature, mainly driven by the geochemistry of the minerals presents in the endorheic character of the basin. The extremely acidic nature of these waters control the Fe species present in them, being FeHSO4+ the mainly Fe specie representing 94% of total. High toxicity of these waters has been detected due to the absence of any diatoms species.

Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial.

PURPOSE: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). PATIENTS AND METHODS: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. RESULTS: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events. CONCLUSION: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.

High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial.

BACKGROUND: The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined. We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy. METHODS: In this open-label, multicentre, phase 3 randomised controlled trial, patients were recruited from ten university hospitals throughout Spain. Eligible patients had clinical stage T1c-T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria. Patients were randomly assigned (1:1) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range 76-82 Gy; short-term androgen deprivation group) or the same treatment followed by 24 months of adjuvant androgen deprivation (long-term androgen deprivation group), stratified by prostate cancer risk group (intermediate risk vs high risk) and participating centre. Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy (flutamide 750 mg per day or bicalutamide 50 mg per day) was added during the first 2 months of treatment. Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175212. FINDINGS: Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50-82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87-92] vs 81% [78-85]; hazard ratio [HR] 1·88 [95% CI 1·12-3·15]; p=0·01). 5-year overall survival (95% [95% CI 93-97] vs 86% [83-89]; HR 2·48 [95% CI 1·31-4·68]; p=0·009) and 5-year metastasis-free survival (94% [95% CI 92-96] vs 83% [80-86]; HR 2·31 [95% CI 1·23-3·85]; p=0·01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3-4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported. INTERPRETATION: Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation. FUNDING: Spanish National Health Investigation Fund, AstraZeneca.

Metal uptake by native plants and revegetation potential of mining sulfide-rich waste-dumps.

Waste dumps resulting from metal exploitation create serious environmental damage, providing soil and water degradation over long distances. Phytostabilization can be used to remediate these mining sites. The present study aims to evaluate the behavior of selected plant species (Erica arborea, Ulex europaeus, Agrostis delicatula, and Cytisus multiflorus) that grow spontaneously in three sulfide-rich waste-dumps (Lapa Grande, Cerdeirinha, and Penedono, Portugal). These sites represent different geological, climatic and floristic settings. The results indicate distinctive levels and types of metal contamination: Penedono presents highest sulfate and metal contents, especially As, with low levels of Fe. In contrast, at Lapa Grande and Cerdeirinha Fe, Mn, and Zn are the dominant metals. In accordance, each waste dump develops a typical plant community, providing a specific vegetation inventory. At Penedono, Agrostis delicatula accumulates As, Pb, Cu, Mn, and Zn, showing higher bioaccumulation factors (BF) for Mn (32.1) and As (24.4). At Cerdeirinha, Ulex europaeus has the highest BF for Pb (984), while at Lapa Grande, Erica arborea presents high BF for Mn (9.8) and Pb (8.1). Regarding TF, low values were obtained for most of the metals, especially As (TF < 1). Therefore, the results obtained from representative plant species suggest appropriate behavior for phytostabilization measures.

Serum Zn levels and Cu/Zn ratios worsen in hemodialysis patients, implying increased cardiovascular risk: a 2-year longitudinal study.

The objective of this study was to analyze serum Zn and Cu concentrations and Cu/Zn ratios in 116 hemodialysis patients (HPs) over a 2-year longitudinal study at four time points (6-month intervals). The relation exerted on these values by 26 biochemical and nutritional indexes, the age and drug consumption of the patients, and the etiology of their disease were also evaluated. A healthy control group (n = 50) was also studied. Mean serum Zn concentrations were lower (p = 0.009) and the Cu/Zn ratios higher (p = 0.009) in HPs than in controls. Serum Cu levels in HP did not differ to those of controls. At all four sampling times, the mean serum Zn levels and Cu/Zn ratios were lower and higher, respectively, in HPs than in the controls. There was a significant reduction in serum Zn levels and an increase in Cu concentrations and Cu/Zn ratios in HPs from the second to the fourth sampling. Serum Zn levels of the HPs diminish with age older than 50 years. Serum Cu levels were significantly higher in patients consuming antihypercalcemic or anti-infarction drugs, whereas serum Cu levels and Cu/Zn ratios were significantly lower in those treated with diuretics. Diminished Zn levels were negatively correlated with low-density lipoprotein (LDL) cholesterol in HPs; however, enhanced Cu/Zn ratios were positively correlated with total cholesterol and LDL cholesterol. Both findings indicate an increased cardiovascular risk. We conclude that this study contributes the first evidence of a correlation between marked dyslipidemia and worsened Cu/Zn ratios in HPs, implying an increased risk of diseases associated with elevated oxidative stress, inflammation, and depressed immune function, such as cardiovascular diseases.

Presence of As in the fluvial network due to AMD processes in the Riotinto mining area (SW Spain): a fuzzy logic qualitative model.

The Tinto River crosses the mining area of Riotinto (Iberian Pyrite Belt, SW Spain), where it receives the highest contribution of contaminants (AMD). In this paper we apply a fuzzy computer tool, PreFuRGe, which allows qualitative interpretation of the data recorded in a database relating to the chemistry of water. Specifically, we aim to find information not likely to be detected by means of classical statistical techniques, and which can help in characterizing and interpreting the behavior of arsenic in a complex system. The conclusions present that the factors which most directly control the presence of total dissolved As are closely linked to the climate and are temperature and rainfall, and therefore pH. As (III) is also shown to be related to temperature and pH. In terms of temperature As (V) is found to operate in a way which is the opposite of As (III). In terms of pH the relationship is not as clear as for As (III). As for rain, the highest As (V) values are compatible with minimum or non-existent rainfall, while minimum values correspond to any value for rainfall, including very high.

Application of cluster analysis to the geochemistry zonation of the estuary waters in the Tinto and Odiel rivers (Huelva, Spain).

The combination of acid water from mines, industrial effluents and sea water plays a determining role in the evolutionary process of the chemical makeup of the water in the estuary of the Tinto and Odiel rivers. This estuary is in the southwest of the Iberian Peninsula and is one of the estuarine systems on the northwest coast of the Gulf of Cádiz. From the statistical treatment of data obtained by analyzing samples of water from this system, which is affected by industrial and mining pollution processes, we can see how the sampling points studied form two large groups depending on whether they receive tidal or fluvial influences. Fluvial input contributes acid water with high concentrations of heavy metal, whereas industrial effluents are responsible for the presence of phosphates, silica and other nutrients. The estuarine system of the Tinto and Odiel Rivers can be divided into three areas--the Tinto estuary, the Odiel estuary and the area of confluence--based on the physical--chemical characteristics of the water.