SERS study of different species of p-aminothiophenol adsorbed on silver nanoparticles

In the present work we have focused the discussion on the experimental and theoretical SERS spectra of the organic compound pATP recorded on silver colloids. The huge SERS of pATP on metal substrates is significantly different from its ordinary Raman spectra due to the formation of a new specie namely p,p’ –dimercaptoazobenzene (DMAB). The features of the SERS spectra of pATP are strongly dependent on many factors as i.e. the laser power density or the laser wavelength but there are still important aspects to understand as, for example, the effect of the concentration that has already been studied before by our group. In this case we have analyzed the effect of the concentration at different wavelengths on the SERS spectra of pATP on silver nanoparticles.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Modelling potential dependent surface-enhanced raman scattering: electric field and charged cluster dual model

The computation of electrochemical systems is very challenging because of the many variables involved. Among them, the effect of the electrode potential is particularly complex to be introduced in atomistic models. In this work, we propose a model where the surface excess of charge has been modelled with the tetrahedral-like clusters [Ag19]+, [Ag20]0 and [Ag19]-. We then modulate the effect of other surface charges implicitly as an external electric field and correlated a calculated magnitude like the electric charge on the adsorbate with the electrode potential, a purely experimental one. This model is tested with the potential-dependent Surface-Enhanced Raman Scattering (SERS) of pyridine. Namely, we investigated the changes in the Raman shifts and relative intensities due to the potential, and evaluated the different contributions (electromagnetic, charge-transfer) to the SERS spectra. Our preliminary results nicely reproduce the experimental trends and reveal that enhancement factors up to 10 to the 7th are achieved when the charge-transfer state interact with the bright local excitations of the metal cluster

Electric field and charged cluster dual model for Potential Depdendent Surface-Enhanced Raman Spectroscopy

The computation of electrochemical systems is very challenging because of the many variables involved.1 Among them, the effect of the electrode potential is particularly complex to be introduced in atomistic models. In this work, we propose a model where the surface excess of charge has been modelled with the tetrahedral-like clusters [Ag19]+, [Ag20]0 and [Ag19]-. We then modulate the effect of other surface charges implicitly as an external electric field and correlated a calculated magnitude like the electric charge on the adsorbate with the electrode potential, a purely experimental one. This model is tested with the potential-dependent Surface-Enhanced Raman Scattering (SERS) of pyridine. Namely, we investigated the changes in the Raman shifts and relative intensities due to the potential, and evaluated the different contributions (electromagnetic, charge-transfer) to the SERS spectra. Our preliminary results nicely reproduce the experimental trends and reveal that enhancement factors up to 107 are achieved when the charge-transfer state interact with the bright local excitations of the metal cluster.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Adiabatic-Molecular Dynamics Generalized Vertical Hessian Approach: A Mixed Quantum Classical Method to Compute Electronic Spectra of Flexible Molecules in the Condensed Phase

We present a general mixed quantum classical method that couples classical molecular dynamics (MD) and vibronic models to compute the shape of electronic spectra of flexible molecules in the condensed phase without, in principle, any phenomenological broadening. It is based on a partition of the nuclear motions of the solute + solvent system in "soft" and "stiff" vibrational modes and an adiabatic hypothesis that assumes that stiff modes are much faster than soft ones. In this framework, the spectrum is rigorously expressed as a conformational integral of quantum vibronic spectra along the stiff coordinates only. Soft modes enter at the classical level through the conformational distribution that is sampled with classical MD runs. In each configuration, reduced-dimensionality quadratic Hamiltonians are built in the space of the stiff coordinates only, thanks to a generalization of the Vertical Hessian harmonic model and an iterative application of projectors in internal coordinates to remove soft modes. Quantum vibronic spectra, specific for each sampled configuration of the soft coordinates, are then computed at the desired temperature with efficient time-dependent techniques, and the global spectrum simply arises from their average. For consistency of the whole procedure, classical MD runs are performed with quantum-mechanically derived force fields, parameterized at the same level of theory selected for generating the quadratic Hamiltonians along the stiff coordinates. Application to N-methyl-6-oxyquinolinium betaine in water, dithiophene in ethanol, and cyanidine in water is presented to show the performance of the methodThis work has received funding from the European Union’s Horizon 2020 research and innovation programme MSCA-ITN under grant agreement no. 765266 (LightDyNAmics). Computational resources provided by the Centro de Cálculo Científico at Universidad Autónoma de Madrid (CCC-UAM) and by SCBI (Supercomputing and Bioinformatics) center of Universidad de Málaga are also acknowledged. D.A. and F.A. acknowledge financial support from Spanish “Ministerio de Economía y Competitividad” (project CTQ2015-65816-R). D.A. acknowledges Fundación Ramón Areces (Spain) for funding his postdoctoral stay at ICCOM-CNR Pisa. J.C. and D.A. acknowledge the Pisa Unit of ICCOM-CNR for hospitality

Voltage selection of physisorbed or chemisorbed 4-cyanobenzoate on a nanostructured silver electrode and the dual electronic structure of charged metal-molecule hybrids.

Applied electric potentials tune SERS wavenumbers due to vibrational Stark effect, but some modes of 4CNB- show two differentiated regions, being redshifted at more negative potentials than the potential of zero charge of the electrode but remain unshifted at positive potentials. DFT calculations have been carried out for a model where 4CNB- is linked through the carboxylate [Agnq-OOC(4CNB-)]q-1 or the nitrile [Agnq-NC(4CNB-)]q-1 to stick-like silver clusters [Agn]q with different densities of charge (qeff =q/n). The comparison between calculated and experimental wavenumber shifts points out that 4CNB- is always adsorbed through the carboxylate. The dual behaviour of the wavenumbers is due to the existence of two types of electronic structure of the metal-molecule hybrid. Physisorbed (P-hybrid, repulsive) or chemisorbed (C-hybrid, attractive) surface complexes are selected by the sign of the surface excess of charge of the electrode. The electronic structure of weakly bonded P-hybrid is very sensitive to the voltage and their wavenumbers are continuously shifted, while the wavenumbers of the strong C-hybrid remain almost unshifted. This result proves the dual nature of the electronic structure of molecules bonded to charged metal electrodes or nanoparticles which can be responsible of the qualitative changes observed in electrochemical or molecular electronics experiments.Junta de Andalucía/FEDER (UMA18-FEDERJA-049 and P18-RT-4592

About the Unexpected Structure and Properties of Molecules Bonded to Metal Nanoclusters.

SERS (Surface-Enhanced Raman Scattering) is a very powerful technique to gain insight into the nature of metal-molecule hybrids on a molecular level. We show the results of combining SERS and theoretical calculations (1) to analyze the subtle electronic structure of metal-molecule (M-A) interfaces, especially to study the dependence of their structure and properties on applied electric potentials or fields. An example of this is the huge efficiency of the potential (EV) in tuning the energies (E) of metal-molecule charge transfer (CT) states. An equivalence between both quantities is expected on the basis of classical electrochemistry (G=E/EV=1 eV/V) but observed energy gains up to G=4 or 5 eV/V can be explained by combining the dependence of the CT energies (E) on the excess of charge of the metal (qeff) (see Graphical Abstract) and the capacitive enhancement located at metallic nanostructures (2). Moreover, theoretical calculations predict a dual electronic structure of the M-A surface complex in the case of charged molecules bonded to charged metals. These two types of surface states of the same hybrid system are of a very different nature and are selected by the sign of the metal charge (qeff). It is predicted that a single M-A complex can be very strongly bonded (chemisorbed) or form weak and very polarizable complexes (physisorbed) depending on the charges of both the ionic species and the surface excess of the metal which is modulated by the applied potential. These two types of complexes determine the properties of the overall system in the ground electronic state, like the behavior of the wavenumbers of the CN stretching band adsorbed on metals (3-4), as well as in excited states, like the forward and reverse metal-molecule CT states of the isonicotinate anion bonded to positive (chemisorbed, G~0 eV/V) or negative (physisorbed, high G) silver clusters (5), respectively (see Graphical Abstract).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The influence of electrode potential on SERS through the electronic structure of nanostructured metal-cyanide interfaces

Experimental and theoretical calculations confirm the existence of two different electronic structures of a surface complex formed by a particular molecule bonded to charged metal electrodes, clusters, or nanoparticles. Each electronic structure of the metal-molecule hybrid system is selected by sign of the surface excess of charge of the metal at potentials more negative or positive than its potential of zero charge (PZC). Surface-enhanced Raman scattering (SERS) of cyanine adsorbed on a silver electrode shows two regions, which are selected by the voltage and characterized by the differentiated response of the vibrational wavenumbers of the ν(CN) stretching band. The combination between the experimental SERS and theoretical DFT calculations has allowed for relating the two regions to chemisorbed (C-hybrid, region A) and physisorbed (P-hybrid, region B) surface complexes, where cyanide is bonded through the carbon on top of a single silver atom of the surface. The electrode potential selects one or another type of electronic structure of the system, which are of different nature having a differentiated response to the applied voltage. Electric potentials tune smoothly the wavenumbers, bond energies, and injected charges of the P-hybrid at more negative potentials than PZC, but the very strong C-hybrid prevents significant changes of these properties at positive excesses of charge. The existence of the dual electronic structure of metal-molecule interfaces might require reinterpreting experiments that are usually discussed by resorting to, for instance, the reorientation of the adsorbate, the formation of complexes with different stoichiometries, the existence of nonequivalent local sites on the surface, or to instrumental artifacts. Moreover, this dual behaviour also determines the properties and responses of technological devices where metal-molecule interfaces are involved.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Ventricular Tachycardia and Early Fibrillation in Patients With Brugada Syndrome and Ischemic Cardiomyopathy Show Predictable Frequency-Phase Properties on the Precordial ECG Consistent With the Respective Arrhythmogenic Substrate

[EN] Background¿ Ventricular fibrillation (VF) has been proposed to be maintained by localized high-frequency sources. We tested whether spectral-phase analysis of the precordial ECG enabled identification of periodic activation patterns generated by such sources. Methods and Results¿Precordial ECGs were recorded from 15 ischemic cardiomyopathy and 15 Brugada syndrome (type 1 ECG) patients during induced VF and analyzed in the frequency-phase domain. Despite temporal variability, induced VF episodes lasting 19.6±7.9 s displayed distinctly high power at a common frequency (shared frequency, 5.7±1.1 Hz) in all leads about half of the time. In patients with Brugada syndrome, phase analysis of shared frequency showed a V1¿V6 sequence as would be expected from patients displaying a type 1 ECG pattern (P<0.001). Hilbert-based phases confirmed that the most stable sequence over the whole VF duration was V1¿V6. Analysis of shared frequency in ischemic cardiomyopathy patients with anteroseptal (n=4), apical (n=3), and inferolateral (n=4) myocardial infarction displayed a sequence starting at V1¿V2, V3¿V4, and V5¿V6, respectively, consistent with an activation origin at the scar location (P=0.005). Sequences correlated with the Hilbert-based phase analysis (P<0.001). Posterior infarction (n=4) displayed no specific sequence. On paired comparison, phase sequences during monomorphic ventricular tachycardia correlated moderately with VF (P<0.001). Moreover, there was a dominant frequency gradient from precordial leads facing the scar region to the contralateral leads (5.8±0.8 versus 5.4±1.1 Hz; P=0.004). Conclusions¿Noninvasive analysis of ventricular tachycardia and early VF in patients with Brugada syndrome and ischemic cardiomyopathy shows a predictable sequence in the frequency-phase domain, consistent with anatomic location of the arrhythmogenic substrate.This study was supported by the National Heart, Lung and Blood Institute (P01-HL039707, P01-HL087226 R01-HL118304); the Spanish Society of Cardiology, Arrhythmia and Electrophysiology Section; the Leducq Foundation, Paris, France; Centro Nacional de Investigaciones Cientificas, Madrid, Spain; Generalitat Valenciana, Valencia, Spain (PROMETEO/2012/030); VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica from the Ministerio de Economia y Competitividad of Spain (TIN2012-37546-C03-01); and the European Commission (European Regional Development Funds [ERDF]-FEDER)Calvo, D.; Atienza, F.; Saiz Rodríguez, FJ.; Martinez, L.; Ávila, P.; Rubín, J.; Herreros, B.... (2015). Ventricular Tachycardia and Early Fibrillation in Patients With Brugada Syndrome and Ischemic Cardiomyopathy Show Predictable Frequency-Phase Properties on the Precordial ECG Consistent With the Respective Arrhythmogenic Substrate. Circulation Arrhythmia and Electrophysiology. 8(5):1133-1143. https://doi.org/10.1161/CIRCEP.114.002717S1133114385Gray, R. A., Jalife, J., Panfilov, A. V., Baxter, W. T., Cabo, C., Davidenko, J. M., … Winfree, A. T. (1995). Mechanisms of Cardiac Fibrillation. Science, 270(5239), 1222-1222. doi:10.1126/science.270.5239.1222Keldermann, R. H., ten Tusscher, K. H. W. J., Nash, M. P., Bradley, C. P., Hren, R., Taggart, P., & Panfilov, A. V. (2009). A computational study of mother rotor VF in the human ventricles. American Journal of Physiology-Heart and Circulatory Physiology, 296(2), H370-H379. doi:10.1152/ajpheart.00952.2008Ten Tusscher, K. H. W. J., Mourad, A., Nash, M. P., Clayton, R. H., Bradley, C. P., Paterson, D. J., … Taggart, P. (2009). Organization of ventricular fibrillation in the human heart: experiments and models. Experimental Physiology, 94(5), 553-562. doi:10.1113/expphysiol.2008.044065CLAYTON, R. H., MURRAY, A., & CAMPBELL, R. W. F. (1995). Evidence for Electrical Organization During Ventricular Fibrillation in the Human Heart. Journal of Cardiovascular Electrophysiology, 6(8), 616-624. doi:10.1111/j.1540-8167.1995.tb00438.xCLAYTON, R. H., MURRAY, A., & CAMPBHLL, R. W. F. (1995). Analysis of the Body Surface ECG Measured in Independent Leads During Ventricular Fibrillation in Humans. Pacing and Clinical Electrophysiology, 18(10), 1876-1881. doi:10.1111/j.1540-8159.1995.tb03835.xArenal, A., del Castillo, S., Gonzalez-Torrecilla, E., Atienza, F., Ortiz, M., Jimenez, J., … Almendral, J. (2004). Tachycardia-Related Channel in the Scar Tissue in Patients With Sustained Monomorphic Ventricular Tachycardias. Circulation, 110(17), 2568-2574. doi:10.1161/01.cir.0000145544.35565.47Warren, M., Guha, P. 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Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study

To compare the effectiveness at ten years of follow-up of radical prostatectomy, brachytherapy and external radiotherapy, in terms of overall survival, prostate cancer-specific mortality and biochemical recurrence. Cohort of men diagnosed with localized prostate cancer (T1/T2 and low/intermediate risk) from ten Spanish hospitals, followed for 10 years. The treatment selection was decided jointly by patients and physicians. Of 704 participants, 192 were treated with open radical retropubic prostatectomy, 317 with I-125 brachytherapy alone, and 195 with 3D external beam radiation. We evaluated overall survival, prostate cancer-specific mortality, and biochemical recurrence. Kaplan-Meier estimators were plotted, and Cox proportional-hazards regression models were constructed to estimate hazard ratios (HR), adjusted by propensity scores. Of the 704 participants, 542 patients were alive ten years after treatment, and a total of 13 patients have been lost during follow-up. After adjusting by propensity score and Gleason score, brachytherapy and external radiotherapy were not associated with decreased 10-year overall survival (aHR = 1.36, p = 0.292 and aHR = 1.44, p = 0.222), but presented higher biochemical recurrence (aHR = 1.93, p = 0.004 and aHR = 2.56, p < 0.001) than radical prostatectomy at ten years of follow-up. Higher prostate cancer-specific mortality was also observed in external radiotherapy (aHR = 9.37, p = 0.015). Novel long-term results are provided on the effectiveness of brachytherapy to control localized prostate cancer ten years after treatment, compared to radical prostatectomy and external radiotherapy, presenting high overall survival, similarly to radical prostatectomy, but higher risk of biochemical progression. These findings provide valuable information to facilitate shared clinical decision-making. Study identifier at ClinicalTrials.gov: NCT01492751

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio