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Based on accumulating evidence of a role of lipid signaling in many physiological and pathophysiological processes including psychiatric diseases, the present data driven analysis was designed to gather information needed to develop a prospective biomarker, using a targeted lipidomics approach covering different lipid mediators. Using unsupervised methods of data structure detection, implemented as hierarchal clustering, emergent self-organizing maps of neuronal networks, and principal component analysis, a cluster structure was found in the input data space comprising plasma concentrations of d = 35 different lipid-markers of various classes acquired in n = 94 subjects with the clinical diagnoses depression, bipolar disorder, ADHD, dementia, or in healthy controls. The structure separated patients with dementia from the other clinical groups, indicating that dementia is associated with a distinct lipid mediator plasma concentrations pattern possibly providing a basis for a future biomarker. This hypothesis was subsequently assessed using supervised machine-learning methods, implemented as random forests or principal component analysis followed by computed ABC analysis used for feature selection, and as random forests, k-nearest neighbors, support vector machines, multilayer perceptron, and naïve Bayesian classifiers to estimate whether the selected lipid mediators provide sufficient information that the diagnosis of dementia can be established at a higher accuracy than by guessing. This succeeded using a set of d = 7 markers comprising GluCerC16:0, Cer24:0, Cer20:0, Cer16:0, Cer24:1, C16 sphinganine, and LacCerC16:0, at an accuracy of 77%. By contrast, using random lipid markers reduced the diagnostic accuracy to values of 65% or less, whereas training the algorithms with randomly permuted data was followed by complete failure to diagnose dementia, emphasizing that the selected lipid mediators were display a particular pattern in this disease possibly qualifying as biomarkers.
The Gini index is a measure of the inequality of a distribution that can be derived from Lorenz curves. While commonly used in, e.g., economic research, it suffers from ambiguity via lack of Lorenz dominance preservation. Here, investigation of large sets of empirical distributions of incomes of the World’s countries over several years indicated firstly, that the Gini indices are centered on a value of 33.33% corresponding to the Gini index of the uniform distribution and secondly, that the Lorenz curves of these distributions are consistent with Lorenz curves of log-normal distributions. This can be employed to provide a Lorenz dominance preserving equivalent of the Gini index. Therefore, a modified measure based on log-normal approximation and standardization of Lorenz curves is proposed. The so-called UGini index provides a meaningful and intuitive standardization on the uniform distribution as this characterizes societies that provide equal chances. The novel UGini index preserves Lorenz dominance. Analysis of the probability density distributions of the UGini index of the World’s counties income data indicated multimodality in two independent data sets. Applying Bayesian statistics provided a data-based classification of the World’s countries’ income distributions. The UGini index can be re-transferred into the classical index to preserve comparability with previous research.
Persistent and, in particular, neuropathic pain is a major healthcare problem with still insufficient pharmacological treatment options. This triggered research activities aimed at finding analgesics with a novel mechanism of action. Results of these efforts will need to pass through the phases of drug development, in which experimental human pain models are established components e.g. implemented as chemical hyperalgesia induced by capsaicin. We aimed at ranking the various readouts of a human capsaicin–based pain model with respect to the most relevant information about the effects of a potential reference analgesic. In a placebo‐controlled, randomized cross‐over study, seven different pain‐related readouts were acquired in 16 healthy individuals before and after oral administration of 300 mg pregabalin. The sizes of the effect on pain induced by intradermal injection of capsaicin were quantified by calculating Cohen's d. While in four of the seven pain‐related parameters, pregabalin provided a small effect judged by values of Cohen's d exceeding 0.2, an item categorization technique implemented as computed ABC analysis identified the pain intensities in the area of secondary hyperalgesia and of allodynia as the most suitable parameters to quantify the analgesic effects of pregabalin. Results of this study provide further support for the ability of the intradermal capsaicin pain model to show analgesic effects of pregabalin. Results can serve as a basis for the designs of studies where the inclusion of this particular pain model and pregabalin is planned.
An easy-to-use model to evaluate conductivities at high and middle latitudes in the height range 70–100 km is presented. It is based on electron density profiles obtained with the EISCAT VHF radar during 11 years and on the neutral atmospheric model MSIS95. The model uses solar zenith angle, geomagnetic activity and season as input parameters. It was mainly constructed to study the properties of Schumann resonances that depend on such conductivity profiles.
Dual-task paradigms encompass a broad range of approaches to measure cognitive load in instructional settings. As a common characteristic, an additional task is implemented alongside a learning task to capture the individual’s unengaged cognitive capacities during the learning process. Measures to determine these capacities are, for instance, reaction times and interval errors on the additional task, while the performance on the learning task is to be maintained. Opposite to retrospectively applied subjective ratings, the continuous assessment within a dual-task paradigm allows to simultaneously monitor changes in the performance related to previously defined tasks. Following the Cognitive Load Theory, these changes in performance correspond to cognitive changes related to the establishment of permanently existing knowledge structures. Yet the current state of research indicates a clear lack of standardization of dual-task paradigms over study settings and task procedures. Typically, dual-task designs are adapted uniquely for each study, albeit with some similarities across different settings and task procedures. These similarities range from the type of modality to the frequency used for the additional task. This results in a lack of validity and comparability between studies due to arbitrarily chosen patterns of frequency without a sound scientific base, potentially confounding variables, or undecided adaptation potentials for future studies. In this paper, the lack of validity and comparability between dual-task settings will be presented, the current taxonomies compared and the future steps for a better standardization and implementation discussed.
Este artigo tem por objetivo analisar comparativamente as semelhanças contidas nas críticas à democracia liberal presentes em alguns trabalhos selecionados de Carl Schmitt (1888-1985) e Robert Kurz (1943-2012). A despeito da estreita associação do primeiro autor com o regime nazista após 1933 e do segundo ser normalmente caracterizado como um pensador marxista (embora bastante crítico ao marxismo “ortodoxo”), são verificáveis inúmeras similitudes entre ambos quando se propõem a analisar as características do liberalismo parlamentar das democracias do século XX. Uma hipótese que pode explicar tais semelhanças seria a influência exercida por Schmitt sobre diversos teóricos da escola de Frankfurt, com os quais Kurz frequentemente dialoga em seus escritos e que foram inspiradores de algumas de suas reflexões – em especial, Walter Benjamin, Theodor Adorno e Max Horkheimer, embora Schmitt também tenha influenciado Franz Neumann, Otto Kirchheimer, Karl Korsch e Herbert Marcuse. Outra via de interpretação abordada aqui se refere à possibilidade de Schmitt ter encontrado, em suas teorias sobre o Estado e sobre o direito, os limites epistemológicos do liberalismo moderno, o que constitui o principal objeto de pesquisa de Kurz e foi tema recorrente nos escritos dos teóricos de Frankfurt.
Este artigo analisa a crítica de Adorno à ontologia de Heidegger. Para tal, utiliza como leitmotiv a interpretação heideggeriana de Kant. Procuraremos mostrar que para Adorno a edificação da ontologia fundamental a partir da filosofia de Kant é uma interpretação indevida desta. Por fim, procura apontar uma possível saída na filosofia de Adorno para o problema da necessidade de fundamentação do discurso filosófico. Tal saída passa pela constatação da importância da arte para a construção da universalidade na filosofia.
A critical role for VEGF and VEGFR2 in NMDA receptor synaptic function and fear-related behavior
(2016)
Vascular endothelial growth factor (VEGF) is known to be required for the action of antidepressant therapies but its impact on brain synaptic function is poorly characterized. Using a combination of electrophysiological, single-molecule imaging and conditional transgenic approaches, we identified the molecular basis of the VEGF effect on synaptic transmission and plasticity. VEGF increases the postsynaptic responses mediated by the N-methyl-d-aspartate type of glutamate receptors (GluNRs) in hippocampal neurons. This is concurrent with the formation of new synapses and with the synaptic recruitment of GluNR expressing the GluN2B subunit (GluNR-2B). VEGF induces a rapid redistribution of GluNR-2B at synaptic sites by increasing the surface dynamics of these receptors within the membrane. Consistently, silencing the expression of the VEGF receptor 2 (VEGFR2) in neural cells impairs hippocampal-dependent synaptic plasticity and consolidation of emotional memory. These findings demonstrated the direct implication of VEGF signaling in neurons via VEGFR2 in proper synaptic function. They highlight the potential of VEGF as a key regulator of GluNR synaptic function and suggest a role for VEGF in new therapeutic approaches targeting GluNR in depression.
Rezension zu: Psychology of Retention:Theory, Research and Practice / Melinde Coetzee, Ingrid L. Potgieter and Nadia Ferreira (Eds.), ISBN:978-3-319-98919-8 Publisher:Springer Nature, 2018, R1600 (Preis SA)