Experimental verification of the metal flux enhancement in a mixture of two metal complexes: the Cd/NTA/glycine and Cd/NTA/citric acid systems

Rigorous computation of the metal flux crossing a limiting surface of a system that contains a mixture of 1 : 1 metal complexes under steady-state planar diffusion in a finite domain and under excess of ligand conditions predicts, for some cases, an enhancement of the metal flux with respect to that expected in a system with independent complexes. Indeed, the coupling of the dissociation kinetics of both complexes can yield higher metal fluxes than expected with important environmental implications. By using the voltammetric techniques AGNES and stripping chronopotentiometry, this paper provides experimental evidence of this enhancement for two systems: Cd/NTA/glycine and Cd/NTA/citric acid. The flux measured in both cases is in good agreement with the flux computed for the global system, exhibiting maximum enhancement ratios above 20%. Theoretical discussion of the flux enhancement factors and of the conditions for this enhancement are also provided

Some Integrable Systems in Nonlinear Quantum Optics

In the paper we investigate the theory of quantum optical systems. As an application we integrate and describe the quantum optical systems which are generically related to the classical orthogonal polynomials. The family of coherent states related to these systems is constructed and described. Some applications are also presented.Comment: 27 page

Multi-Pattern Visual Statistical Learning in Monolinguals and Bilinguals

To date, the impact of bilingualism on statistical learning remains unclear. Here we test a novel visual statistical learning task that affords simultaneous learning of two types of regularities: co-occurrence regularities between pairs of elements and the co-occurrence of visual features that could define categories. We compared performance by English monolinguals, Spanish-Catalan bilinguals and Spanish-English bilinguals, as previous studies have suggested that bilinguals might be more open than monolinguals to the presence of multiple regularities, though no previous studies have tested the learning of multiple patterns within a single task. We demonstrated that both monolingual and bilingual participants could learn the co-occurrence probabilities and the features that define categories. To the best of our knowledge, this study is the first to demonstrate that learners can extract co-occurrence regularities along two dimensions in the visual modality. However, we did not detect significant differences in performance across groups. We close by discussing the implications for the growing literature on bilingualism and statistical learning

Absence of Gradients and Nernstian Equilibrium Stripping (AGNES) for the determination of [Zn2+] in estuarine waters

Zinc (Zn) has been classified as a 'Specific Pollutant' under Annex VIII of the EU Water Framework Directive by two thirds of the EU member states. As a result, the UK Environmental Quality Standard (EQS) for Transitional and Coastal (TrAC) Waters has been reduced from 612 nM to 121 nM total dissolved Zn. It is widely accepted that the free metal ion ([Zn2+]) is the most bioavailable fraction, but there are few techniques available to determine its concentration in these waters. In this work, Absence of Gradients and Nernstian Equilibrium Stripping (AGNES) has been applied, for the first time, to determine [Zn2+] in estuarine waters. The AGNES method had a mean RSD of +/- 18%, a (deposition time dependent) limit of detection of 0.73 nM and a [Zn2+] recovery of 112 +/- 19% from a certified reference material (BCR-505; Estuarine Water). AGNES results for 13 estuarine samples (salinity 0.1-31.9) compared well (P = 0.02) with Competitive Ligand Exchange Cathodic Stripping Voltammetry (CLE-AdCSV) except for one sample. AGNES requires minimal sample manipulation, is unaffected by adsorption of interfering species at the electrode surface and allows direct determination of free zinc ion concentrations. Therefore AGNES results can be used in conjunction with ecotoxicological studies and speciation modelling to set and test compliance with water quality standards.This PhD research is co-funded by the International Zinc Association, the International Copper Association, and Plymouth University. Warm thanks to Dr. Chris Cooper for his helpful comments, and to Marjan Heidarkhan Tehrani and Mireia Lao Martinez for their invaluable help and advice in the laboratory

Baseline neutrophil-to-lymphocyte ratio as a predictive and prognostic biomarker in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel versus abiraterone or enzalutamide in the CARD study

Abiraterona; Cabazitaxel; Factor pronósticoAbiraterona; Cabazitaxel; Factor pronòsticAbiraterone; Cabazitaxel; Prognostic factorBackground There is growing evidence that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC). In the CARD study (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and OS versus abiraterone or enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative androgen-receptor-targeted agent (ARTA). Here, we investigated NLR as a biomarker. Patients and methods CARD was a multicenter, open-label study that randomized patients with mCRPC to receive cabazitaxel (25 mg/m2 every 3 weeks) versus abiraterone (1000 mg/day) or enzalutamide (160 mg/day). The relationships between baseline NLR [< versus ≥ median (3.38)] and rPFS, OS, time to prostate-specific antigen progression, and prostate-specific antigen response to cabazitaxel versus ARTA were evaluated using Kaplan–Meier estimates. Multivariable Cox regression with stepwise selection of covariates was used to investigate the prognostic association between baseline NLR and OS. Results The rPFS benefit with cabazitaxel versus ARTA was particularly marked in patients with high NLR {8.5 versus 2.8 months, respectively; hazard ratio (HR) 0.43 [95% confidence interval (CI) 0.27-0.67]; P < 0.0001}, compared with low NLR [7.5 versus 5.1 months, respectively; HR 0.69 (95% CI 0.45-1.06); P = 0.0860]. Higher NLR (continuous covariate, per 1 unit increase) independently associated with poor OS [HR 1.05 (95% CI 1.02-1.08); P = 0.0003]. For cabazitaxel, there was no OS difference between patients with high versus low NLR (15.3 versus 12.9 months, respectively; P = 0.7465). Patients receiving an ARTA with high NLR, however, had a worse OS versus those with low NLR (9.5 versus 13.3 months, respectively; P = 0.0608). Conclusions High baseline NLR predicts poor outcomes with an ARTA in patients with mCRPC previously treated with docetaxel and the alternative ARTA. Conversely, the activity of cabazitaxel is retained irrespective of NLR.This work was supported by Sanofi Genzyme (no grant number). The authors were responsible for all content and editorial decisions and received no honoraria for development of this manuscript

From theory to practice: assessing the use of radiotherapy in population based cancer registries

Purpose or Objective: Planning for radiotherapy services requires evidence based information on the optimum and the actual use of this therapy in a population in order to assess the potential gaps in the utilization of external beam radiotherapy

Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer

Càncer de pròstata; Metàstasi neoplàsica; ImmunoteràpiaCáncer de próstata; Metástasis neoplásica; InmunoterapiaProstate cancer; Metastatic neoplasm; ImmunotherapyPURPOSE PROSTVAC, a viral vector–based immunotherapy, prolonged median overall survival (OS) by 8.5 months versus placebo in metastatic castration-resistant prostate cancer in a phase II study. This phase III study further investigated those findings. PATIENTS AND METHODS Patients were randomly assigned to PROSTVAC (Arm V; n = 432), PROSTVAC plus granulocyte-macrophage colony-stimulating factor (Arm VG; n = 432), or placebo (Arm P; n = 433), stratified by prostate-specific antigen (less than 50 ng/mL v 50 ng/mL or more) and lactate dehydrogenase (less than 200 v 200 U/L or more). Primary end point was OS. Secondary end points were patients alive without events (AWE)—namely, radiographic progression, pain progression, chemotherapy initiation, or death—at 6 months and safety. The study design was a superiority trial of PROSTVAC (Arm V or Arm VG) versus Arm P. Three interim analyses were planned. RESULTS At the third interim analysis, criteria for futility were met and the trial was stopped early. Neither active treatment had an effect on median OS (Arm V, 34.4 months; hazard ratio, 1.01; 95% CI, 0.84 to 1.20; P = .47; Arm VG, 33.2 months; hazard ratio, 1.02; 95% CI, 0.86 to 1.22; P = .59; Arm P, 34.3 months). Likewise, AWE at 6 months was similar (Arm V, 29.4%; odds ratio, 0.96; 95% CI, 0.71 to 1.29; Arm VG, 28.0%; odds ratio, 0.89; 95% CI, 0.66 to 1.20; placebo, 30.3%). Adverse events were similar for the treatment and placebo groups, with the most common being injection site reactions (62% to 72%) and fatigue (21% to 24%). Arrhythmias were the most common cardiac-related events (1.4% to 3.5%). There were no reports of either myocarditis or pericarditis. Serious treatment-related events occurred in less than 1% of all patients. CONCLUSION Whereas PROSTVAC was safe and well tolerated, it had no effect on OS or AWE in metastatic castration-resistant prostate cancer. Combination therapy is currently being explored in clinical trials.Supported by Bavarian Nordic, the National Institute for Health Research Biomedical Research Centre at the Royal Marsden National Health Service Foundation Trust, and the Institute of Cancer Research. Funded in part by National Cancer Institute Cancer Center Support Grant No. P30-CA008748 and the Center for Cancer Research, National Cancer Institute.P30 CA008748/CA/NCI NIH HHS/United States DH_/Department of Health/United Kingdo

Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer: Secondary analysis of COU-AA-301 and COU-AA-302

Abiraterone acetate; Metastatic castration-resistant prostate cancer; MetforminAcetato de abiraterona; Cáncer de próstata metastásico resistente a la castración; MetforminaAcetat d'abiraterona; Càncer de pròstata resistent a la castració metastàtic; MetforminaBackground The associations of metformin and statins with overall survival (OS) and prostate specific antigen response rate (PSA-RR) in trials in metastatic castration-resistant prostate cancer remain unclear. Objective To determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone (AAP) influence OS and PSA-RR. Design, setting and participant COU-AA-301 and COU-AA-302 patients were stratified by metformin and statin use. Cox proportional hazards models were used to estimate hazards ratio (HR) stratified by concomitant medications, and a random effects model was used to pool HR. We compared PSA-RR using Chi χ2 test. Results In COU-AA-301-AAP, metformin was associated with improved PSA-RR (41.1% versus 28.6%) but not prolonged OS. In COU-AA-301-placebo-P, there was no association between metformin and prolonged OS or PSA-RR. In COU-AA-302-AAP, metformin was associated with prolonged OS (adjHR 0.69, 95% CI 0.48–0.98) and improved PSA-RR (72.7% versus 60.0%). In COU-AA-302-P, metformin was associated with prolonged OS (adjHR 0.66, 95% CI 0.47–0.93). In pooled analysis, OS was prolonged among those treated with metformin (pooled HR 0.77, 95% CI 0.62–0.95).In COU-AA-301-AAP, statins were associated with an improved OS (adjHR 0.76, 95% CI 0.62–0.93), while there was no difference in COU-AA-301-P. There was no association with statins and OS in either COU-AA-302 groups. When pooling HR, OS was prolonged among those treated with statins (pooled HR 0.78, 95% CI 0.68–0.88). Conclusion Within the limitations of post-hoc sub-analyses, metformin and statins are associated with a prolonged OS and increased PSA-RR, particularly in combination with AAP

FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation.

Uterine sarcomas are rare but deadly malignancies without effective treatment. Immunotherapy is a promising new approach to treat these tumors but has shown heterogeneous effects in sarcoma patients. With the goal of identifying key factors for improved patient treatment, we characterized the tumor immune landscape in 58 uterine sarcoma cases with full clinicopathological annotation. Immune cell characterization revealed the overall prevalence of FOXP3+ cells and pro-tumor M2-like macrophages. Hierarchical clustering of patients showed four tumor type-independent immune signatures, where infiltration of FOXP3+ cells and M1-like macrophages associated with favorable prognosis. High CD8+/FOXP3+ ratio in UUS and ESS correlated with poor survival, upregulation of immunosuppressive markers, extracellular matrix (ECM)-related genes and proteins, and YAP activation. This study shows that uterine sarcomas present distinct immune signatures with prognostic value, independent of tumor type, and suggests that targeting the ECM could be beneficial for future treatments

Engineering the microstructure and magnetism of La2_2CoMnO6_6 thin films by tailoring oxygen stoichiometry

We report on the magnetic and structural properties of ferromagnetic-insulating La$_2$CoMnO$_6$ thin films grown on top of (001) STO substrates by means of RF sputtering technique. Careful structural analysis, by using synchrotron X-ray diffraction, allows identifying two different crystallographic orientations that are closely related to oxygen stoichiometry and to the features (coercive fields and remanence) of the hysteresis loops. Both Curie temperature and magnetic hysteresis turn out to be dependent on the oxygen stoichiometry. In situ annealing conditions allow tailoring the oxygen content of the films, therefore controlling their microstructure and magnetic properties