Why dried blood spots are an ideal tool for CYP1A2 phenotyping

Background and Objective: Dried blood spot (DBS) sampling has gained wide interest in bioanalysis during the last decade and has already been successfully applied in pharmacokinetic and phenotyping studies. However, all of the available phenotyping studies used small datasets and did not include a systematic evaluation of DBS-specific parameters. The latter is important since several of these factors still challenge the breakthrough of DBS in routine practice. In this study, caffeine and paraxanthine are determined in capillary DBS, venous DBS, whole blood and plasma for cytochrome P450 (CYP) 1A2 phenotyping. The aim of this study was to explore the usefulness of DBS as a tool for CYP1A2 phenotyping. Methods: A CYP1A2 phenotyping study was conducted in 73 healthy volunteers who received a 150 mg oral dose of caffeine. Six hours post-administration, caffeine and paraxanthine concentrations and paraxanthine:caffeine molar concentration ratios, i.e., the actual CYP1A2 phenotyping indices, were determined in capillary DBS (obtained by non-volumetric application, direct from the fingertip), venous DBS, whole blood, and plasma. Furthermore, the impact of DBS-specific parameters, including hematocrit, volume spotted, and punch location, was evaluated. Results: Concentrations of caffeine and paraxanthine in capillary DBS were, respectively, on average 12.7 and 13.8 % lower than those in venous DBS and 31.5 and 33.1 % lower than those in plasma. While these differences were statistically significant (p = 0.053). This ratio also alleviated the impact of hematocrit and volume spotted. Conclusions: Using the largest DBS-based phenotyping study to date, we have demonstrated that CYP1A2 phenotyping in capillary DBS is a valid and convenient alternative for the classical plasma-based approach. Additionally, we have provided an objective basis as to why DBS are an ideal tool for CYP1A2 phenotyping

European Security in the Context of Migration - Measures to Protect Borders and Security Aspects Connected with Migration

The aim of this article is to assess the existing development of migrant crisis in connection with the divided member states of the European Union. Based on the comparison of migrant flows, study of the measures adopted in order to prevent migration and analysis of security risks of migration presented in the article it has been proven that there is a direct correlation between migration and an increased rate of terrorist attacks in Europe. The elimination of smuggling groups and the support of migrants' countries of origin have helped to mitigate migration pressure. The outcomes of the article confirm that despite the adoption of legal and technical measures by the European Union in order to secure the external border of the Schengen Area, European countries do not share the same view of how to solve the migrant crisis. The outcome of migration issue solution is to provide relevant information to the expert public in order to support a stable and safe European Union. It is an equal partnership of all the European Union member states in all the areas that is of the highest priority in order to guarantee the above state

Environmental Support for Naval Operations—a Profile of Fleet Numerical Weather Facility, Monterey, California

The article of record as published may be found at https://www.jstor.org/stable/2625144

A Small, Additonal, Added–on Life Speaking. Remarks on the Vitalism in Giorgio Agamben's Critical Theory

Agamben’s thought gives us an interesting set of tools and references to critically analyse the logic of sovereignty haunting even the best intentions of Western biopolitics. As an alternative to the inherently disastrous logic of inclusive exclusion, he puts forward a strong vitalist, ontological way of thinking. This paper is an enquiry into whether that alternative is really valid. As far as his publications allow (since the “pars construens” of his Homo Sacer project is still to be published), the answer to this question must be negative. A careful reading of the passages on language in both Homo Sacer I and III (Remnants of Auschwitz), is illuminating in this regard. This is because the passages on language in which Agamben develops his alternative logic (for instance, the ones on bearing witness) do not overcome the logic of sovereignty denounced in the usual – representationalist – way of thinking the biopolitical. Those passages give no adequate answer to the representationalist way of treating the same problems, saying that the logic of sovereignty – of inclusive exclusion – is  the logic we have to deal with even to find solutions for the disaster that logic has provoked and is still able to provoke

Dried blood spots in toxicology : from the cradle to the grave?

About a century after its first described application by Ivar Bang, the potential of sampling via dried blood spots (DBS) as an alternative for classical venous blood sampling is increasingly recognized. Perhaps best known is the use of DBS in newborn screening programs, ignited by the hallmark paper by Guthrie and Susi half a century ago. However, it is only recently that both academia and industry have recognized the many advantages that DBS sampling may offer for bioanalytical purposes, as reflected by the strong increase in published reports during the last few years. Currently, major DBS applications include newborn screening for metabolic disorders, epidemiological surveys (e. g. HIV monitoring), therapeutic drug monitoring (TDM), as well as toxicology. In this review, we provide a comprehensive overview of the distinct subdisciplines of toxicology for which DBS sampling has been applied. DBS sampling for toxicological evaluation has been performed from birth until autopsy, aiming at the assessment of therapeutic drugs, drugs of abuse, environmental contaminants, toxins, as well as (trace) elements, with applications situated in fields as toxicokinetics, epidemiology and environmental and forensic toxicology. We discuss the strengths and limitations of DBS in the different subdisciplines and provide future prospects for the use of this promising sampling technique in toxicology