Optimization of Nanoparticle-Based SERS Substrates through Large-Scale Realistic Simulations

Surface-enhanced Raman scattering (SERS) has become a widely used spectroscopic technique for chemical identification, providing unbeaten sensitivity down to the singlemolecule level. The amplification of the optical near field produced by collective electron excitations plasmons in nanostructured metal surfaces gives rise to a dramatic increase by many orders of magnitude in the Raman scattering intensities from neighboring molecules. This effect strongly depends on the detailed geometry and composition of the plasmonsupporting metallic structures. However, the search for optimized SERS substrates has largely relied on empirical data, due in part to the complexity of the structures, whose simulation becomes prohibitively demanding. In this work, we use state-of-the-art electromagnetic computation techniques to produce predictive simulations for a wide range of nanoparticle-based SERS substrates, including realistic configurations consisting of random arrangements of hundreds of nanoparticles with various morphologies. This allows us to derive rules of thumb for the influence of particle anisotropy and substrate coverage on the obtained SERS enhancement and optimum spectral ranges of operation. Our results provide a solid background to understand and design optimized SERS substrates.Peer ReviewedPostprint (published version

Clinical pharmacology facing the real-world setting: Pharmacovigilance, pharmacoepidemiology and the economic evaluation of drugs

Adverse drug reaction; Effectiveness; PharmacoeconomicsReacció adversa als fàrmacs; Eficàcia; FarmacoeconomiaReacción adversa a medicamentos; Eficacia; FarmacoeconomíaTraditionally, clinical pharmacology has focused its activities on drug-organism interaction, from an individual or collective perspective. Drug efficacy assessment by performing randomized clinical trials and analysis of drug use in clinical practice by carrying out drug utilization studies have also been other areas of interest. From now on, Clinical pharmacology should move from the analysis of the drug-individual interaction to the analysis of the drug-individual-society interaction. It should also analyze the clinical and economic consequences of the use of drugs in the conditions of normal clinical practice, beyond clinical trials. The current exponential technological development that facilitates the analysis of real-life data offers us a golden opportunity to move to all these other areas of interest. This review describes the role that clinical pharmacology has played at the beginning and during the evolution of pharmacovigilance, pharmacoepidemiology and economic drug evaluations in Spain. In addition, the challenges that clinical pharmacology is going to face in the following years in these three areas are going to be outlined too

Risk of Myocardial Infarction among new users of calcium supplements alone or combined with vitamin D: a population-based case-control study

A population-based case-control study was conducted to evaluate the risk of acute myocardial infarction among new users of calcium supplements either in monotherapy (CaM) or in combination with vitamin D (CaD). A total of 23,025 cases and 114,851 controls randomly sampled from the underlying cohort and matched with cases by age, sex, and index date were included. New users of CaM and CaD were categorized as current users, recent users, past users, and nonusers. We computed adjusted odds ratios (AORs) and their 95% confidence intervals (CIs) among current users as compared with nonusers through a conditional logistic regression. No increased risk was associated with CaM overall (59 cases (0.26%) and 273 controls (0.24%); AOR = 0.80; 95% CI 0.59?1.09), nor was it found in any of the conditions examined. Instead, the use of CaD was associated with a decreased risk (275 cases (1.19%) and 1,160 controls (1.45%); AOR = 0.78; 95% CI 0.67?0.90), dose and duration-dependent, and particularly evident in patients with a high cardiovascular risk (AOR = 0.59; 95% CI 0.43?0.81).Instituto de Salud Carlos IIIMinisterio de Ciencia e Innovació

Influenza vaccine and risk of acute myocardial infarction in a population-based case-control study

Objective To assess the relationship between influenza vaccination and risk of a first acute myocardial infarction (AMI) in the general population by different epidemic periods. Methods This is a population-based case?control study carried out in BIFAP (Base de datos para la investigación farmacoepidemiológica en atención primaria), over 2001?2015, in patients aged 40?99 years. Per each incident AMI case, five controls were randomly selected, individually matched for exact age, sex and index date (AMI diagnosis). A patient was considered vaccinated when he/she had a recorded influenza vaccination at least 14 days before the index date within the same season. The association between influenza vaccination and AMI risk was assessed through a conditional logistic regression, computing adjusted ORs (AOR) and their respective 95% CIs. The analysis was performed overall and by each of the three time epidemic periods per study year (pre-epidemic, epidemic and postepidemic). Results We identified 24 155 AMI cases and 120 775 matched controls. Of them, 31.4% and 31.2%, respectively, were vaccinated, yielding an AOR of 0.85 (95% CI 0.82 to 0.88). No effect modification by sex, age and background cardiovascular risk was observed. The reduced risk of AMI was observed shortly after vaccination and persisted over time. Similar results were obtained during the pre-epidemic (AOR=0.87; 95% CI 0.79 to 0.95), epidemic (AOR=0.89; 95% CI 0.82 to 0.96) and postepidemic (AOR=0.83; 95% CI 0.79 to 0.87) periods. No association was found with pneumococcal vaccine (AOR=1.10; 95% CI 1.06 to 1.15). Conclusions Results are compatible with a moderate protective effect of influenza vaccine on AMI in the general population, mostly in primary prevention, although bias due to unmeasured confounders may partly account for the results.Instituto de Salud Carlos IIIMinisterio de Ciencia e InnovaciónHospital Universitario Príncipe de Asturia

Selective Serotonin Reuptake Inhibitors and Risk of Noncardioembolic Ischemic Stroke: A Nested Case-Control Study

BACKGROUND: Multiple studies have reported that the use of selective serotonin reuptake inhibitors (SSRIs) is associated with an increased risk of ischemic stroke; however, this finding may be the result of a confounding by indication. We examined the association using different approaches to minimize such potential bias. METHODS: A nested case-control study was carried out in a Spanish primary health-care database over the study period 2001 to 2015. Cases were patients sustaining an ischemic stroke with no sign of cardioembolic or unusual cause. For each case, up to 5 matched controls (for exact age, sex, and index date) were randomly selected. Antidepressants were divided in 6 pharmacological subgroups according to their mechanism of action. The current use of SSRIs (use within a 30-day window before index date) was compared with nonuse, past use (beyond 365 days) and current use of other antidepressants through a conditional logistic regression model to obtain adjusted odds ratios and 95% CI. Only initiators of SSRIs and other antidepressants were considered. RESULTS: A total of 8296 cases and 37 272 matched controls were included. Of them, 255 (3.07%) were current users of SSRIs among cases and 834 (2.24%) among controls, yielding an adjusted odds ratio of 1.14 (95% CI, 0.97?1.34) as compared with nonusers, 0.94 (95% CI, 0.77?1.13) as compared with past-users and 0.74 (95% CI, 0.58?0.93) as compared with current users of other antidepressants. No relevant differences were found by duration (?1, >1 year), sex, age (<70, ?70 years old) and background vascular risk. CONCLUSIONS: The use of SSRIs was not associated with an increased risk of noncardioembolic ischemic stroke. On the contrary, as compared with other antidepressants, SSRIs appeared to be protective.Instituto de Salud Carlos IIIMinisterio de Ciencia e InnovaciónFondo Europeo de Desarrollo Regiona

Association of oral bisphosphonates with cardioembolic ischemic stroke: a nested case-control study

Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and noncardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants. Methods: We performed a case-control study nested in a cohort of patients aged 40?99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered. Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01?1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10?1.66) and 1.03 (95% CI: 0.88?1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR?1 year = 1.10; 95% CI:0.82?1.49; AOR>1?3 years = 1.41; 95% CI: 1.01?1.97; AOR>3 years = 1.81; 95% CI:1.25?2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1 year = 0.59; 0.30?1.16). An interaction between oral bisphosphonates and calcium supplements was suggested. Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.Research Foundation of the University Hospital Príncipe de Asturia

Risk of Acute Myocardial Infarction Among New Users of Allopurinol According to Serum Urate Level: A Nested Case-Control Study

Abstract: Objectives: To test the hypothesis that allopurinol reduces the risk of acute myocardial infarction (AMI) in hyperuricemic patients and to assess whether the effect is dependent on dose, duration and serum uric acid (SUA) level attained after treatment. Methods: Nested case-control study over the period 2002?2015. From a cohort of patients aged 40?99 years old, we identified incident AMI cases and randomly selected five controls per case, matched for exact age, sex and index date. Adjusted odds ratios (AOR) and 95% CI were computed through unconditional logistic regression. Only new users of allopurinol were considered. Results: A total of 4697 AMI cases and 18,919 controls were included. Allopurinol use was associated with a reduced risk of AMI mainly driven by duration of treatment (AOR ?180 days = 0.71; 95% CI: 0.60?0.84). Among long-term users (>180 days), the reduced risk was only observed when the SUA level attained was below 7 mg/dL (AOR7mg/dL = 1.04; 95% CI: 0.75?1.46; p for trend = 0.001). A dose-effect was observed but faded out once adjusted for the SUA level attained. The reduced risk of AMI occurred in both patients with gout and patients with asymptomatic hyperuricemia. Conclusions: The results confirm a cardioprotective effect of allopurinol which is strongly dependent on duration and SUA level attained after treatment

Antimicrobial-resistant Invasive Escherichia coli, Spain

Antimicrobial resistance, particularly to fluoroquinolones and third-generation cephalosporins, is increasing in E. coli in Spain

Ethics guidelines for the creation and use of registries for biomedical research purposes

The clinical information stored in registries and records of different types is a fundamental tool for biomedical research. Up until just a few years ago, hardly any limitations existed on the creation and use of epidemiological registries or the use of information from pre-existing records for research purposes. This situation has changed substantially due mainly to the growing importance current laws place upon the safeguarding of the privacy and confidentiality of personal data. Although the legal framework is already quite explicit, a certain degree of leeway exists for ethical debate and prudence advice for the purpose of conducting valid, useful research with this information which will also respect the rights of the subjects and the laws in force. These guidelines deal with those aspects which have been considered relevant from an ethical standpoint in the handling of records and registries for research-related purposes, including not only the use but also the creation proper of the registries. A total of twenty-four recommendations are provided, grouped into ten sections: warranting of the creation of registry, organization and definition of responsibilities, scientific validity of the research project, ethical requirements of the collections of anonymous and anonymized data, ethical requirements of the registries including personal data, uses of medical records for research purposes, use of historical records of deceased individuals, contact with the research subjects, notification of results and review by a Research Ethics Committee. La información clínica almacenada en registros de diverso tipo constituye una herramienta fundamental para la investigación biomédica. Hasta hace pocos años la creación y uso de registros epidemiológicos, o la utilización de información procedente de registros pre-existentes con fines de investigación, apenas tenía limitaciones. Esta situación ha cambiado de modo sustancial debido básicamente a la creciente importancia que las leyes actuales conceden a la protección de la intimidad, la privacidad y la confidencialidad de los datos de carácter personal. Aunque el marco legal es ya muy explícito, hay un cierto espacio para la deliberación ética y el consejo prudente, al objeto de realizar con dicha información una investigación válida y útil y que, al mismo tiempo, respete los derechos de los sujetos y la legalidad vigente. En las presentes directrices se abordan aquellos aspectos que se han considerado relevantes desde un punto de vista ético en el manejo de registros con fines de investigación, incluyendo no sólo el uso sino la creación misma del registro. Se proporcionan 24 recomendaciones agrupadas en 10 apartados: justificación de la creación de un registro, organización y definición de responsabilidades, validez científica del proyecto de investigación, requisitos éticos de las colecciones de datos anónimos y de los registros anonimizados, requisitos éticos de los registros que contienen datos de carácter personal, usos de la historia clínica con fines de investigación, uso de registros históricos y de personas fallecidas, contacto con los sujetos de investigación, comunicación de resultados y revisión por un Comité de Ética de la Investigación

Results obtained from the multiple geodetic observations at Lorca (Murcia, Spain) subsidence area

Trabajo presentado en el AGU (American Geophysical Union) Fall Meeting: Advancing Earth and Space Science, celebrado en Washington D.C. (Estados Unidos), del 10 al 14 de diciembre de 2018The Lorca region, located in the Alto Guadalentín Basin, southern Spain, shows the highest subsidence rates recorded in Europe (about 10 cm/yr). It is produced by a long-term aquifer exploitation (González and Fernández, 2011; Bonì et al., 2014). This process has been studied in various works using interferometric synthetic aperture radar (InSAR) with images acquired from different satellites (ERS and ENVISAT radar data spanning the 1992 – 2007 period; ALOS PALSAR data for the period 2007–2010; and COSMO-SkyMed data for the period 2011–2012). González et al. (2012) established a relationship between the crustal unloading produced by the groundwater overexploitation and the stress change on the regional active tectonic faults in relation with the May 2008 Lorca earthquake. Those previous studies, based on InSAR and using either ascending or descending acquisitions, assumed that the surface displacement direction is entirely vertical. However, it is important to obtain the complete 3D motion field in order to perform a correct interpretation of the observations, as well as to carry out an advanced numerical model of the aquifer evolution, to be considered for sustainable management plans of groundwater resources and hazard assessments. To achieve this goal, GNSS surveys have been carried out from 2015 to 2018, showing the regional 3D displacement field associated to the exploitation of the aquifer (Prieto et al., 2016; Fernández et al. 2017). Also, simultaneous ascending and descending InSAR observations have been used, along with structural gravimetry (Camacho et al., 2015) and microgravity to study the subsidence area in a more complete geodetic way. We present the results obtained from all those techniques, their comparison, and the interpretation results using different inversion techniques (Tiampo et al., 2011; Camacho et al., 2011, 2015; Cannavò et al., 2015).Peer reviewe