Determination of drugs used in combined cardiovascular therapy

Cardiovascular diseases are nowadays the first cause of mortality worldwide, causing around the 30% of global deaths each year. The risk of suffering from cardiovascular illnesses is strongly related to some factors such as hypertension, high cholesterol levels, diabetes, obesity The combination of these different risk factors is known as metabolic syndrome and it is considered a pandemic due to the high prevalence worldwide. The pathology of the disorders implies a combined cardiovascular therapy with drugs which have different targets and mechanisms of action, to regulate each factor separately. The simultaneous analysis of these drugs turns interesting but it is a complex task since the determination of multiple substances with different physicochemical properties and physiological behavior is always a challenge for the analytical chemist. The complexity of the biological matrices and the difference in the expected concentrations of some analytes require the development of extremely sensitive and selective determination methods. The aim of this work is to fill the gap existing in this field of the drug analysis, developing analytical methods capable of quantifying the different drugs prescribed in combined cardiovascular therapy simultaneously. Liquid chromatography andem mass spectrometry (LCMS/MS) has been the technique of choice throughout the main part of this work, due to the high sensitivity and selectivity requirements.

Development of new applications of inductively coupled plasma mass spectrometry (ICP-MS) hyphenated with different sample introduction systems

225 p. : il. Texto en español con conclusiones en inglés

The Uniform World Model: A Methodology for Predicting the Health Impacts of Air Pollution

47 p.

Mass spectrometry coupled to imaging techniques: The better the view the greater the challenge

These are definitively exciting times for membrane lipid researchers. Once considered just as the cell membrane building blocks, the important role these lipids play is steadily being acknowledged. The improvement occurred in mass spectrometry techniques (MS) allows the establishment of the precise lipid composition of biological extracts. However, to fully understand the biological function of each individual lipid species, we need to know its spatial distribution and dynamics. In the past 10 years, the field has experienced a profound revolution thanks to the development of MS-based techniques allowing lipid imaging (MSI). Images reveal and verify what many lipid researchers had already shown by different means, but none as convincing as an image: each cell type presents a specific lipid composition, which is highly sensitive to its physiological and pathological state. While these techniques will help to place membrane lipids in the position they deserve, they also open the black box containing all the unknown regulatory mechanisms accounting for such tailored lipid composition. Thus, these results urges to different disciplines to redefine their paradigm of study by including the complexity revealed by the MSI techniques.

Spatial-temporal excess mortality patterns of the 1918-1919 influenza pandemic in Spain

Background: The impact of socio-demographic factors and baseline health on the mortality burden of seasonal and pandemic influenza remains debated. Here we analyzed the spatial-temporal mortality patterns of the 1918 influenza pandemic in Spain, one of the countries of Europe that experienced the highest mortality burden. Methods: We analyzed monthly death rates from respiratory diseases and all-causes across 49 provinces of Spain, including the Canary and Balearic Islands, during the period January-1915 to June-1919. We estimated the influenza-related excess death rates and risk of death relative to baseline mortality by pandemic wave and province. We then explored the association between pandemic excess mortality rates and health and socio-demographic factors, which included population size and age structure, population density, infant mortality rates, baseline death rates, and urbanization. Results: Our analysis revealed high geographic heterogeneity in pandemic mortality impact. We identified 3 pandemic waves of varying timing and intensity covering the period from Jan-1918 to Jun-1919, with the highest pandemic-related excess mortality rates occurring during the months of October-November 1918 across all Spanish provinces. Cumulative excess mortality rates followed a south-north gradient after controlling for demographic factors, with the North experiencing highest excess mortality rates. A model that included latitude, population density, and the proportion of children living in provinces explained about 40% of the geographic variability in cumulative excess death rates during 1918-19, but different factors explained mortality variation in each wave. Conclusions: A substantial fraction of the variability in excess mortality rates across Spanish provinces remained unexplained, which suggests that other unidentified factors such as comorbidities, climate and background immunity may have affected the 1918-19 pandemic mortality rates. Further archeo-epidemiological research should concentrate on identifying settings with combined availability of local historical mortality records and information on the prevalence of underlying risk factors, or patient-level clinical data, to further clarify the drivers of 1918 pandemic influenza mortality.

Predictive score for mortality in patients with COPD exacerbations attending hospital emergency departments

Background: Limited information is available about predictors of short-term outcomes in patients with exacerbation of chronic obstructive pulmonary disease (eCOPD) attending an emergency department (ED). Such information could help stratify these patients and guide medical decision-making. The aim of this study was to develop a clinical prediction rule for short-term mortality during hospital admission or within a week after the index ED visit. Methods: This was a prospective cohort study of patients with eCOPD attending the EDs of 16 participating hospitals. Recruitment started in June 2008 and ended in September 2010. Information on possible predictor variables was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up. Main short-term outcomes were death during hospital admission or within 1 week of discharge to home from the ED, as well as at death within 1 month of the index ED visit. Multivariate logistic regression models were developed in a derivation sample and validated in a validation sample. The score was compared with other published prediction rules for patients with stable COPD. Results: In total, 2,487 patients were included in the study. Predictors of death during hospital admission, or within 1 week of discharge to home from the ED were patient age, baseline dyspnea, previous need for long-term home oxygen therapy or non-invasive mechanical ventilation, altered mental status, and use of inspiratory accessory muscles or paradoxical breathing upon ED arrival (area under the curve (AUC) = 0.85). Addition of arterial blood gas parameters (oxygen and carbon dioxide partial pressures (PO2 and PCO2)) and pH) did not improve the model. The same variables were predictors of death at 1 month (AUC = 0.85). Compared with other commonly used tools for predicting the severity of COPD in stable patients, our rule was significantly better. Conclusions: Five clinical predictors easily available in the ED, and also in the primary care setting, can be used to create a simple and easily obtained score that allows clinicians to stratify patients with eCOPD upon ED arrival and guide the medical decision-making process.

Hartle's model within the general theory of perturbatiye matchings: the change in mass

Hartle's model provides the most widely used analytic framework to describe isolated compact bodies rotating slowly in equilibrium up to second order in perturbations in the context of General Relativity. Apart from some explicit assumptions, there are some implicit, like the "continuity" of the functions in the perturbed metric across the surface of the body. In this work we sketch the basics for the analysis of the second order problem using the modern theory of perturbed matchings. In particular, the result we present is that when the energy density of the fluid in the static configuration does not vanish at the boundary, one of the functions of the second order perturbation in the setting of the original work by Hartle is not continuous. This discrepancy affects the calculation of the change in mass of the rotating star with respect to the static configuration needed to keep the central energy density unchanged.

The center of mass and center of charge of the electron

9th Biennial Conference on Classical and Quantum Relativistic Dynamics of Particles and Fields (IARD)