77 research outputs found
The typology of vocational education and training cooperation between Germany and China
Germany and China have been engaged in a wide range of vocational education and training (VET) cooperation activities since the 1980s. To clarify what organizations have been involved and what project types exist within VET cooperation, a semistructured survey had been conducted for collecting data. By this approach, 99 VET project profiles with 258 organizations related were detected. To analyse these projects and organizations, the âgeneral key factor model of sustainabilityâ is used to structure the analysis framework. In this framework, âcooperation typeâ, âcontent typeâ and âproject durationâ were considered as the three fundamental criteria for further categorization. On this basis, seven cooperation types were created by the organizations involved, three content types were established by the goal of the project and three project duration were distinguished by the time planned for the project. The result shows that governmental organizations are the main actors who play a major role in the Sino-German VET cooperation. However, numerically, German private organizations participated more in VET cooperation rather than Chinese private organizations. Civil social organizations show no significant function. Meanwhile, different cooperation types show different projects' emphasis: Type G (Governmental) projects focus on building or promoting on the organization level; Type Gâ+âP (Governmentalâ+âPrivate) projects tend to objectives on the individual and system level; Type Gâ+âC (Governmentalâ+âCivil) projects occur more often at an individual level; Type Gâ+âPâ+âC (Governmentalâ+âPrivateâ+âCivil) projects tend to pursue goals on organizational or system level
Altered metabolic pathways elucidated via untargeted in vivo toxicometabolomics in rat urine and plasma samples collected after controlled application of a human equivalent amphetamine dose
Amphetamine is widely consumed as drug of abuse due to its stimulating and cognitive enhancing effects. Since amphetamine has been on the market for quite a long time and it is one of the most commonly used stimulants worldwide, to date there is still limited information on its effects on the metabolome. In recent years, untargeted toxicometabolomics have been increasingly used to study toxicity-related pathways of such drugs of abuse to find and identify important endogenous and exogenous biomarkers. In this study, the acute effects of amphetamine intake on plasma and urinary metabolome in rats were investigated. For this purpose, samples of male Wistar rats after a single dose of amphetamine (5 mg/kg) were compared to a control group using an untargeted metabolomics approach. Analysis was performed using normal and reversed phase liquid chromatography coupled to high-resolution mass spectrometry using positive and negative ionization mode. Statistical evaluation was performed using Welchâs two-sample t test, hierarchical clustering, as well as principal component analysis. The results of this study demonstrate a downregulation of amino acids in plasma samples after amphetamine exposure. Furthermore, four new potential biomarkers N-acetylamphetamine, N-acetyl-4-hydroxyamphetamine, N-acetyl-4-hydroxyamphetamine glucuronide, and amphetamine succinate were identified in urine. The present study complements previous data and shows that several studies are necessary to elucidate altered metabolic pathways associated with acute amphetamine exposure
Model Selection in Variational Mixed Effects Models
Variational inference is an alternative estimation technique for Bayesian
models. Recent work shows that variational methods provide consistent
estimation via efficient, deterministic algorithms. Other tools, such as model
selection using variational AICs (VAIC) have been developed and studied for the
linear regression case. While mixed effects models have enjoyed some study in
the variational context, tools for model selection are lacking. One important
feature of model selection in mixed effects models, particularly longitudinal
models, is the selection of the random effects which in turn determine the
covariance structure for the repeatedly sampled outcome. To address this, we
derive a VAIC specifically for variational mixed effects (VME) models. We also
implement a parameter-efficient VME as part of our study which reduces any
general random effects structure down to a single subject-specific score. This
model accommodates a wide range of random effect structures including random
intercept and slope models as well as random functional effects. Our VAIC can
model and perform selection on a variety of VME models including more classic
longitudinal models as well as longitudinal scalar-on-function regression. As
we demonstrate empirically, our VAIC performs well in discriminating between
correctly and incorrectly specified random effects structures. Finally, we
illustrate the use of VAICs for VMEs on two datasets: a study of lead levels in
children and a study of diffusion tensor imaging
Method development for quantitative determination of seven statins including four active metabolites by means of high-resolution tandem mass spectrometry applicable for adherence testing and therapeutic drug monitoring
Background: Statins are used to treat and prevent cardiovascular diseases (CVDs) by reducing the total serum cholesterol concentration. Unfortunately, dose-related side effects and sub-optimal response, attributed to non-adherence amongst others, were described. Therefore, a fast and sensitive liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) method for adherence testing and therapeutic drug monitoring of all currently marketed statins and their active metabolites in human blood plasma should be developed, validated and tested for applicability. Methods:Atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as ortho- and para-hydroxy-atorvastatin, lovastatin hydroxy acid and simvastatin hydroxy acid were included and several internal standards (IS) tested. Validation was performed according to the guideline of the European Medicines Agency including selectivity, carry-over, accuracy, precision, matrix effects, dilution integrity and analyte stability. Finally, applicability was tested using 14 patient samples submitted for regular toxicological analysis. Results: Due to an analytical interference of atorvastatin-d5, diazepam-d5 and pentobarbital-d5 were chosen as IS for positive and negative ionization mode, respectively. All statins and metabolites fulfilled the validation acceptance criteria except for fluvastatin, which could not be quantified reliably and reproducibly, most probably due to instability. Analyses of human plasma samples revealed concentrations of statins and metabolites below the reference plasma concentrations in the case of eight patients. However, nothing was known concerning patientsâ adherence and time between intake and sampling. Conclusions: An LC-HRMS/MS method for identification and quantification of atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and four active metabolites was successfully developed and applicability demonstrated
In Vitro and In Vivo Toxicometabolomics of the Synthetic Cathinone PCYP Studied by Means of LC-HRMS/MS
Synthetic cathinones are one important group amongst new psychoactive substances (NPS)
and limited information is available regarding their toxicokinetics and -dynamics. Over the past few
years, nontargeted toxicometabolomics has been increasingly used to study compound-related effects
of NPS to identify important exogenous and endogenous biomarkers. In this study, the effects of
the synthetic cathinone PCYP (2-cyclohexyl-1-phenyl-2-(1-pyrrolidinyl)-ethanone) on in vitro and
in vivo metabolomes were investigated. Pooled human-liver microsomes and blood and urine of
male Wistar rats were used to generate in vitro and in vivo data, respectively. Samples were analyzed
by liquid chromatography and high-resolution mass spectrometry using an untargeted metabolomics
workflow. Statistical evaluation was performed using univariate and multivariate statistics. In total,
sixteen phase I and one phase II metabolite of PCYP could be identified as exogenous biomarkers.
Five endogenous biomarkers (e.g., adenosine and metabolites of tryptophan metabolism) related
to PCYP intake could be identified in rat samples. The present data on the exogenous biomarker
of PCYP are crucial for setting up analytical screening procedures. The data on the endogenous
biomarker are important for further studies to better understand the physiological changes associated
with cathinone abuse but may also serve in the future as additional markers for an intake
Comparison of Three Untargeted Data Processing Workflows for Evaluating LC-HRMS Metabolomics Data
The evaluation of liquid chromatography high-resolution mass spectrometry (LC-HRMS)
raw data is a crucial step in untargeted metabolomics studies to minimize false positive findings.
A variety of commercial or open source software solutions are available for such data processing.
This study aims to compare three different data processing workflows (Compound Discoverer 3.1,
XCMS Online combined with MetaboAnalyst 4.0, and a manually programmed tool using R) to
investigate LC-HRMS data of an untargeted metabolomics study. Simple but highly standardized
datasets for evaluation were prepared by incubating pHLM (pooled human liver microsomes)
with the synthetic cannabinoid A-CHMINACA. LC-HRMS analysis was performed using normaland reversed-phase chromatography followed by full scan MS in positive and negative mode.
MS/MS spectra of significant features were subsequently recorded in a separate run. The outcome of
each workflow was evaluated by its number of significant features, peak shape quality, and the results
of the multivariate statistics. Compound Discoverer as an all-in-one solution is characterized by its
ease of use and seems, therefore, suitable for simple and small metabolomic studies. The two open
source solutions allowed extensive customization but particularly, in the case of R, made advanced
programming skills necessary. Nevertheless, both provided high flexibility and may be suitable for
more complex studies and questions
Addendum: Hemmer, S., et al. Comparison of Three Untargeted Data Processing Workflows for Evaluating LC-HRMS Metabolomics Data. Metabolites 2020, 10, 378
The authors wish to make the following comment to this paper [...
âThe Bard meets the Doctorâ â ComputergestĂŒtzte Identifikation intertextueller ShakespearebezĂŒge in der Science Fiction-Serie Dr. Who.
A single abstract from the DHd-2019 Book of Abstracts.Sofern eine editorische Arbeit an dieser Publikation stattgefunden hat, dann bestand diese aus der Eliminierung von Bindestrichen in Ăberschriften, die aufgrund fehlerhafter Silbentrennung entstanden sind, der Vereinheitlichung von Namen der Autor*innen in das Schema "Nachname, Vorname" und/oder der Trennung von Ăberschrift und UnterĂŒberschrift durch die Setzung eines Punktes, sofern notwendig
Beliefs about the Strauss-Kahn case in France and Germany: Political orientation and sexual aggression myths as local versus global predictors
Helmke S, Kobusch P-R, Rees J, Meyer T, Bohner G. Beliefs about the Strauss-Kahn case in France and Germany: Political orientation and sexual aggression myths as local versus global predictors. International Journal of Conflict and Violence. 2014;8(1):171-186.In May 2011, Dominique Strauss-Kahn, head of the International Monetary Fund and a prominent member of the French Socialist Party, was charged with attempted rape. Extensive media coverage led people across the globe to speculate about intentions and responsibilities. While the case was pending, we conducted two parallel Internet surveys, with French and German participants (*N* = 1,314). We examined how strongly exoneration of the alleged perpetrator depended on acceptance of modern myths about sexual aggression (AMMSA) and identity attributes that are temporarily salient as a function of local context (gender, political left-right orientation, nationality). AMMSA was a global predictor of exonerating the alleged perpetrator across national sub-samples, whereas the predictive power of gender and left-right orientation varied locally: For French respondents, left-wing political attitudes predicted exoneration of the alleged perpetrator, whereas only for German respondents, being male predicted exoneration. We conclude that the interplay of global (sexual aggression myths) and local (social identification) factors affects the lay assessment of ambiguous cases of sexual violence
Species-conserved mechanisms of cognitive flexibility in complex environments
Flexible decision making in complex environments is a hallmark of intelligent behavior but the underlying learning mechanisms and neural computations remain elusive. Through a combination of behavioral, computational and electrophysiological analysis of a novel multidimensional rule-learning paradigm, we show that both rats and humans sequentially probe different behavioral strategies to infer the task rule, rather than learning all possible mappings between environmental cues and actions as current theoretical formulations suppose. This species-conserved process reduces task dimensionality and explains both observed sudden behavioral transitions and positive transfer effects. Behavioral strategies are represented by rat prefrontal activity and strategy-related variables can be decoded from magnetoencephalography signals in human prefrontal cortex. These mechanistic findings provide a foundation for the translational investigation of impaired cognitive flexibility.One-Sentence SummaryBoth rats and humans use behavioral strategies to infer task rules during multidimensional rule-learning
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