Effects of lactate and acetate on the determination of serum ethyl glucuronide by CZE

The analysis of ethyl glucuronide (EtG), a marker of recent alcohol consumption, in serum with an optimized CZE assay is reported. The method uses a 0.1-mm id fused-silica capillary of 50 cm effective length that is coated with linear polyacrylamide, a pH 4.4 nicotinic acid/epsilon-aminocaproic acid (EACA) BGE, reversed polarity and indirect analyte detection. The assay is based on a 1:1 dilution of serum with deionized water and has LODs for EtG, lactate and acetate of 3.8 x 10(-7) M, 2.60 x 10(-6 )M and 2.18 x 10(-6 )M, respectively. Separation of EtG from endogenous macro- and microcomponents (anionic serum components of high and low concentration, respectively) and its quantification are shown to be possible for a wide range of lactate (stacker) and acetate (destacker) concentrations, macrocomponents that have an impact on the CZE behavior of EtG and that change after intake of ethanol. The assay has been successfully applied to the analysis of EtG, lactate and acetate in (i) sera of volunteers that ingested known amounts of alcohol and (ii) samples of patients that were classified (teetotalers and social drinkers vs. alcohol abusers) via analysis of carbohydrate-deficient transferrin.

Relation of depression to various markers of coagulation and fibrinolysis in patients with and without coronary artery disease

BACKGROUND: It has been suggested that changes in blood coagulation and fibrinolysis might explain the observed association between depression and coronary artery disease (CAD). So far, only a few coagulation factors have been investigated in this regard, and the results were not consistent. DESIGN: The aim of our study was to analyse a broad range of coagulation and fibrinolytic factors, with emphasis on factors directly involved in clot formation and degradation or reflecting coagulation activation, in patients with CAD and controls without CAD, as assessed by coronary angiography, who also underwent a diagnostic procedure for depression. METHODS: We screened 306 patients with CAD and controls without CAD for depression using the Hospital Anxiety and Depression Scale and Allgemeine Depressions Skala-L questionnaires. In participants with positive screening result, diagnosis of major depression was confirmed or excluded by a structured interview. We analysed the following coagulation and fibrinolytic factors: fibrinogen, prothrombin fragment F1+2, factor XIII A-subunit, factor XIII B-subunit, tissue plasminogen activator, plasminogen activator inhibitor-1, thrombin-activable fibrinolysis inhibitor, and D-dimer. RESULTS: We did not observe significant associations between depression and CAD, nor between depression and cardiovascular risk factors. Coagulation and fibrinolytic factors showed no differences between patients with CAD and controls, but they were associated with several cardiovascular risk factors. Depression was not associated with coagulation and fibrinolytic factors. No associations were found either when both CAD and depression were taken into account. CONCLUSION: Our study gives no evidence that there is a significant relation among depression, CAD, and blood coagulation and fibrinolysis.

A feasibility study on model-based evaluation of kidney perfusion measured by means of FAIR prepared true-FISP arterial spin labeling (ASL) on a 3-T MR scanner

RATIONALE AND OBJECTIVES: A feasibility study on measuring kidney perfusion by a contrast-free magnetic resonance (MR) imaging technique is presented. MATERIALS AND METHODS: A flow-sensitive alternating inversion recovery (FAIR) prepared true fast imaging with steady-state precession (TrueFISP) arterial spin labeling sequence was used on a 3.0-T MR-scanner. The basis for quantification is a two-compartment exchange model proposed by Parkes that corrects for diverse assumptions in single-compartment standard models. RESULTS: Eleven healthy volunteers (mean age, 42.3 years; range 24-55) were examined. The calculated mean renal blood flow values for the exchange model (109 +/- 5 [medulla] and 245 +/- 11 [cortex] ml/min - 100 g) are in good agreement with the literature. Most important, the two-compartment exchange model exhibits a stabilizing effect on the evaluation of perfusion values if the finite permeability of the vessel wall and the venous outflow (fast solution) are considered: the values for the one-compartment standard model were 93 +/- 18 (medulla) and 208 +/- 37 (cortex) ml/min - 100 g. CONCLUSION: This improvement will increase the accuracy of contrast-free imaging of kidney perfusion in treatment renovascular disease.

Atorvastatin does not alter serum levels of sCD95 and sCD95L in multiple sclerosis

Elimination of autoreactive T cells by apoptosis is critical for restricting immune responses to self-antigens. An errant lytic interaction between the CD95 death receptor and its ligand CD95L is presumed to be involved in the pathogenesis of multiple sclerosis (MS). Statins are promising agents for the treatment of MS and were shown to modulate levels of soluble death receptors. Here, we evaluated the in vivo effects by interferon (IFN)-beta and atorvastatin on soluble CD95 (sCD95) and sCD95L in serum of patients with MS. Concentrations of sCD95 and sCD95L did not show any differences between MS and healthy control subjects. In patients with MS, treatment with IFN-beta increased serum levels of sCD95 and sCD95L significantly (P < 0.01 and P < 0.05 respectively). Addition of atorvastatin to IFN-beta did not alter serum levels of sCD95 and sCD95L significantly. Our study suggests that atorvastatin does not affect IFN-beta-induced increases of the soluble death receptors in the serum of patients with MS.

Linkage in narratives: A comparison between monolingual speakers of French and Italian, and early and late French-Italian bilinguals

In the course of language acquisition learners have to deal with the task of producing narrative texts that are coherent across a range of conceptual domains (space, time, entities) -- both within as well as across utterances. The organization of information is analyzed in this study, on the basis of retellings of a silent film, in terms of devices used in the coordination and subordination of events within the narrative sequence. The focus on subordination reflects a core grammatical difference between Italian and French, as Italian is a null-subject language while French is not. The implications of this contrast for information structure include differences in topic management within the sequence of events. The present study investigates in how far Italian-French bilingual speakers acquire the patterns of monolingual speakers of Italian. It compares how early and late bilinguals of these two languages proceed when linking information in narratives in Italian.

Cost-effectiveness of ticagrelor and generic clopidogrel in patients with acute coronary syndrome in Switzerland

QUESTION UNDER STUDY The aim of this study was to evaluate the cost-effectiveness of ticagrelor and generic clopidogrel as add-on therapy to acetylsalicylic acid (ASA) in patients with acute coronary syndrome (ACS), from a Swiss perspective. METHODS Based on the PLATelet inhibition and patient Outcomes (PLATO) trial, one-year mean healthcare costs per patient treated with ticagrelor or generic clopidogrel were analysed from a payer perspective in 2011. A two-part decision-analytic model estimated treatment costs, quality-adjusted life years (QALYs), life years and the cost-effectiveness of ticagrelor and generic clopidogrel in patients with ACS up to a lifetime at a discount of 2.5% per annum. Sensitivity analyses were performed. RESULTS Over a patient's lifetime, treatment with ticagrelor generates an additional 0.1694 QALYs and 0.1999 life years at a cost of CHF 260 compared with generic clopidogrel. This results in an Incremental Cost Effectiveness Ratio (ICER) of CHF 1,536 per QALY and CHF 1,301 per life year gained. Ticagrelor dominated generic clopidogrel over the five-year and one-year periods with treatment generating cost savings of CHF 224 and 372 while gaining 0.0461 and 0.0051 QALYs and moreover 0.0517 and 0.0062 life years, respectively. Univariate sensitivity analyses confirmed the dominant position of ticagrelor in the first five years and probabilistic sensitivity analyses showed a high probability of cost-effectiveness over a lifetime. CONCLUSION During the first five years after ACS, treatment with ticagrelor dominates generic clopidogrel in Switzerland. Over a patient's lifetime, ticagrelor is highly cost-effective compared with generic clopidogrel, proven by ICERs significantly below commonly accepted willingness-to-pay thresholds.

When language of instruction and language of application differ: Cognitive costs of bilingual mathematics learning

Bilingual education programs implicitly assume that the acquired knowledge is represented in a language-independent way. This assumption, however, stands in strong contrast to research findings showing that information may be represented in a way closely tied to the specific language of instruction and learning. The present study aims to examine whether and to which extent cognitive costs appear during arithmetic learning when language of instruction and language of retrieving differ. Thirty-nine high school students participating in a bilingual education program underwent a four-day training on multiplication and subtraction problems in one language (German or French), followed by a test session in which they had to solve trained as well as untrained problems in both languages. We found that cognitive costs related to language switching appeared for both arithmetic operations. Implications of our findings are discussed with respect to bilingual education as well as to cognitive mechanisms underlying different arithmetic operations.

Interactions of climate and land use documented in the varved sediments of Seebergsee in the Swiss Alps

This paper presents a multiproxy high-resolution study of the past 2600 years for Seebergsee, a small Swiss lake with varved sediments at the present tree-line ecotone. The laminae were identified as varves by a numerical analysis of diatom counts in the thin-sections. The hypothesis of two diatom blooms per year was corroborated by the 210Pb and 137Cs chronology. A period of intensive pasturing during the ‘Little Ice Age’ between ad 1346 and ad 1595 is suggested by coprophilous fungal spores, as well as by pollen indicators of grazing, by the diatom-inferred total phosphorus, by geochemistry and by documentary data. The subsequent re-oligotrophication of the lake took about 88 years, as determined by the timelag between the decline of coprophile fungal spores and the restoration of pre-eutrophic nutrient conditions. According to previous studies of latewood densities from the same region, cold summers around ad 1600 limited the pasturing at this altitude. This demonstrated the socio-economic impact of a single climatic event. However, the variance partitioning between the effects of land use and climate, which was applied for the whole core, revealed that climate independent of land use and time explained only 1.32% of the diatom data, while land use independent of climate and time explained 15.7%. Clearly land use in‘ uenced the lake, but land use was not always driven by climate. Other factors beside climate, such as politics or the introduction of fertilizers in the seventeenth and eighteenth centuries also in‘ uenced the development of Alpine pasturing.

On the initiation of boudinage and folding instabilities in layered elasto-visco-plastic solids - Insights from natural microstructures and numerical simulations

The present understanding of the initiation of boudinage and folding structures is based on viscosity contrasts and stress exponents, considering an intrinsically unstable state of the layer. The criterion of localization is believed to be prescribed by geometry-material interactions, which are often encountered in natural structures. An alternative localization phenomenon has been established for ductile materials, in which instability emerges for critical material parameters and loading rates from homogeneous conditions. In this thesis, conditions are sought under which this type of instability prevails and whether localization in geological materials necessarily requires a trigger by geometric imperfections. The relevance of critical deformation conditions, material parameters and the spatial configuration of instabilities are discussed in a geological context. In order to analyze boudinage geometries, a numerical eigenmode analysis is introduced. This method allows determining natural frequencies and wavelengths of a structure and inducing perturbations on these frequencies. In the subsequent coupled thermo-mechanical simulations, using a grain size evolution and end-member flow laws, localization emerges when material softening through grain size sensitive viscous creep sets in. Pinch-and-swell structures evolve along slip lines through a positive feedback between the matrix response and material bifurcations inside the layer, independent from the mesh-discretization length scale. Since boudinage and folding are considered to express the same general instability, both structures should arise independently of the sign of the loading conditions and for identical material parameters. To this end, the link between material to energy instabilities is approached by means of bifurcation analyses of the field equations and finite element simulations of the coupled system of equations. Boudinage and folding structures develop at the same critical energy threshold, where dissipative work by temperature-sensitive creep overcomes the diffusive capacity of the layer. This finding provides basis for a unified theory for strain localization in layered ductile materials. The numerical simulations are compared to natural pinch-and-swell microstructures, tracing the adaption of grain sizes, textures and creep mechanisms in calcite veins. The switch from dislocation to diffusion creep relates to strain-rate weakening, which is induced by dissipated heat from grain size reduction, and marks the onset of continuous necking. The time-dependent sequence uncovers multiple steady states at different time intervals. Microstructurally and mechanically stable conditions are finally expressed in the pinch-and-swell end members. The major outcome of this study is that boudinage and folding can be described as the same coupled energy-mechanical bifurcation, or as one critical energy attractor. This finding allows the derivation of critical deformation conditions and fundamental material parameters directly from localized structures in the field.