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Root infinitives on Twitter
(2017)
Background: Evidence that home telemonitoring (HTM) for patients with chronic heart failure (CHF) offers clinical benefit over usual care is controversial as is evidence of a health economic advantage. Therefore the CardioBBEAT trial was designed to prospectively assess the health economic impact of a dedicated home monitoring system for patients with CHF based on actual costs directly obtained from patients’ health care providers.
Methods: Between January 2010 and June 2013, 621 patients (mean age 63,0 ± 11,5 years, 88 % male) with a confirmed diagnosis of CHF (LVEF ≤ 40 %) were enrolled and randomly assigned to two study groups comprising usual care with and without an interactive bi-directional HTM (Motiva®). The primary endpoint was the Incremental Cost-Effectiveness Ratio (ICER) established by the groups’ difference in total cost and in the combined clinical endpoint “days alive and not in hospital nor inpatient care per potential days in study” within the follow up of 12 months. Secondary outcome measures were total mortality and health related quality of life (SF-36, WHO-5 and KCCQ).
Results: In the intention-to-treat analysis, total mortality (HR 0.81; 95% CI 0.45 – 1.45) and days alive and not in hospital (343.3 ± 55.4 vs. 347.2 ± 43.9; p = 0.909) were not significantly different between HTM and usual care. While the resulting primary endpoint ICER was not positive (-181.9; 95% CI −1626.2 ± 1628.9), quality of life assessed by SF-36, WHO-5 and KCCQ as a secondary endpoint was significantly higher in the HTW group at 6 and 12 months of follow-up.
Conclusions: The first simultaneous assessment of clinical and economic outcome of HTM in patients with CHF did not demonstrate superior incremental cost effectiveness compared to usual care. On the other hand, quality of life was improved. It remains open whether the tested HTM solution represents a useful innovative approach in the recent health care setting.
Preclinical assessment of penetration not only in intact, but also in barrier‐disrupted skin is important to explore the surplus value of novel drug delivery systems, which can be specifically designed for diseased skin. Here, we characterized physical and chemical barrier disruption protocols for short‐term ex vivo skin cultures with regard to structural integrity, physiological and biological parameters. Further, we compared the penetration of dexamethasone (Dex) in different nanoparticle‐based formulations in stratum corneum, epidermis and dermis extracts of intact vs. barrier‐disrupted skin as well as by dermal microdialysis at 6, 12 and 24 hours after topical application. Dex was quantified by liquid‐chromatography ‐ tandem‐mass spectrometry (LC‐MS/MS). Simultaneously, we investigated the Dex efficacy by interleukin (IL) analysis. Tape‐stripping (TS) and 4 hours sodium lauryl sulfate 5 % (SLS) exposure were identified as highly effective barrier disruption methods assessed by reproducible transepidermal water loss (TEWL) changes and IL‐6/8 increase which was more pronounced in SLS‐treated skin. The barrier state has also a significant impact on the Dex penetration kinetics: for all formulations, TS highly increased dermal Dex concentration despite the fact that nanocrystals quickly and effectively penetrated both, intact and barrier‐disrupted skin reaching significantly higher dermal Dex concentration after 6 hours compared to Dex cream. The surplus value of encapsulation in ethyl cellulose nanocarriers could mostly be observed when applied on intact skin, in general showing a delayed Dex penetration. Estimation of cytokines was limited due to the trauma caused by probe insertion. In summary, ex vivo human skin is a highly interesting short‐term preclinical model for the analysis of penetration and efficacy of novel drug delivery systems.
Emergency Care in Germany being re-assessed Hybrid Medical Care Model Seen As Potential Answer
(2017)
Nanocarriers
(2017)
Der Leserbrief fokussiert in weiten Teilen auf das Gutachterwesen, weshalb wir ausschließlich auf die inhaltlichen Punkte im Zusammenhang mit unserer Arbeit eingehen. Untersucht wurden schmerzpsychologische Interventionen, wie beschrieben definiert als psychologische Interventionen, deren primäres Ziel die Schmerzreduktion war.
Die extrahierten Zielgrößen, wie Lebensqualität oder Depressivität, ergaben sich aus den in den Primärstudien untersuchten Hauptoutcomes und nicht aus der Suchstrategie.
Zur Einschätzung der methodischen Qualität der Primärstudien konnte ein Kriterium des von Johannsen und Kollegen [2] gebildeten Scores nicht berücksichtigt werden, da die eingeschlossenen Primärstudien keine metaanalytische Zusammenfassung erlaubten. Stellt man dies in Rechnung, bleibt die Vergleichbarkeit beider Werte erhalten.
Die Evidenzsynthese erfolgte narrativ in Text- und Tabellenform, d. h. in Form einer strukturierten Zusammenfassung und Diskussion von Studien [1].
Um unsere Arbeit zu fokussieren, hätten wir eine weitergehende Gegenüberstellung wie auch eine Überprüfung von Zitaten und Übersetzungen selbstverständlich vorgenommen, wenn wir den Hinweis dazu vor Publikation erhalten hätten.
As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously reevaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment. (C) 2017 Elsevier Inc. All rights reserved.
Recently a multitude of empirically derived damage models have been applied to project future tropical cyclone (TC) losses for the United States. In their study (Geiger et al 2016 Environ. Res. Lett. 11 084012) compared two approaches that differ in the scaling of losses with socio-economic drivers: the commonly-used approach resulting in a sub-linear scaling of historical TC losses with a nation's affected gross domestic product (GDP), and the disentangled approach that shows a sub-linear increase with affected population and a super-linear scaling of relative losses with per capita income. Statistics cannot determine which approach is preferable but since process understanding demands that there is a dependence of the loss on both GDP per capita and population, an approach that accounts for both separately is preferable to one which assumes a specific relation between the two dependencies. In the accompanying comment, Rybski et al argued that there is no rigorous evidence to reach the conclusion that high-income does not protect against hurricane losses. Here we affirm that our conclusion is drawn correctly and reply to further remarks raised in the comment, highlighting the adequateness of our approach but also the potential for future extension of our research.
S-test results for the USGS and RELM forecasts. The differences between the simulated log-likelihoods and the observed log-likelihood are labelled on the horizontal axes, with scaling adjustments for the 40year.retro experiment. The horizontal lines represent the confidence intervals, within the 0.05 significance level, for each forecast and experiment. If this range contains a log-likelihood difference of zero, the forecasted log-likelihoods are consistent with the observed, and the forecast passes the S-test (denoted by thin lines). If the minimum difference within this range does not contain zero, the forecast fails the S-test for that particular experiment, denoted by thick lines. Colours distinguish between experiments (see Table 2 for explanation of experiment durations). Due to anomalously large likelihood differences, S-test results for Wiemer-Schorlemmer.ALM during the 10year.retro and 40year.retro experiments are not displayed. The range of log-likelihoods for the Holliday-et-al.PI forecast is lower than for the other forecasts due to relatively homogeneous forecasted seismicity rates and use of a small fraction of the RELM testing region.
DPP4 inhibition prevents AKI
(2017)
Since the Shallow Structure Hypothesis (SSH) was first put forward in 2006, it has inspired a growing body of research on grammatical processing in nonnative (L2) speakers. More than 10 years later, we think it is time for the SSH to be reconsidered in the light of new empirical findings and current theoretical assumptions about human language processing. The purpose of our critical commentary is twofold: to clarify some issues regarding the SSH and to sketch possible ways in which this hypothesis might be refined and improved to better account for L1 and L2 speakers’ performance patterns.
The keynote article (Mayberry & Kluender, 2017) makes an important contribution to questions concerning the existence and characteristics of sensitive periods in language acquisition. Specifically, by comparing groups of non-native L1 and L2 signers, the authors have been able to ingeniously disentangle the effects of maturation from those of early language exposure. Based on L1 versus L2 contrasts, the paper convincingly argues that L2 learning is a less clear test of sensitive periods. Nevertheless, we believe Mayberry and Kluender underestimate the evidence for maturational factors in L2 learning, especially that coming from recent research.
In recent years, “transnationalism” has become a key concept for historians and other scholars in the humanities and social sciences. However, its overuse threatens to dilute what would otherwise be a distinct approach with promising heuristic potential. This danger seems especially pronounced when the notion of transnationalism is applied to Jewish history, which, paradoxically, most scholars would agree, is at its core transnational. Many studies have analyzed how Jewries in different times and places, from the biblical era to the present, have been shaped by people, ideas, texts, and institutions that migrated across state lines and between cultures. So what is new about transnationalism in Jewish Studies? What new insights does it offer?
American Jewry offers an obvious arena to test transnationalism’s significance as an approach to historical research within Jewish studies. As a “nation of nations,” the United States is made up of a distinct and unique society, built on ideas of diversity and pluralism, and transcending old European concepts of nation and state. The transformative incorporation in American life of cultural, political, and social traditions brought from abroad is one feature of this distinctiveness. American Jewish history and culture, in particular, are best understood in the context of interaction with Jews in other places, both because of American Jews’ roots in and continued entanglement with Europe, and because of their differences from other Jews.
These considerations guided the participants in a roundtable that formed a prologue to an international conference held July 20–22, 2016, at the School of Jewish Theology at the University of Potsdam and the Center for Jewish Studies Berlin-Brandenburg, Germany. The conference title, “Re-Framing American Jewish History and Thought: New Transnational Perspectives,” indicated the organizers’ conviction that the transnational approach does have the potential to shed fresh light on the American Jewish experience. The participants were asked to bring their experiences to the table, in an effort to clarify what transnationalism might mean for American Jewish Studies, and where it might yield new approaches and insights.
The conference brought together some thirty scholars of various disciplines from Europe, Israel, and the United States. In addition to exploring a relatively new approach (at least, in the field of American Jewish Studies), the conference also served a second purpose: to further the interest in American Jewry as a subject of scholarly attention in countries outside the U.S., where the topic has been curiously neglected. The assumption underlying the conference was that a transnational perspective on American Jewry would bring to bear the particular interests and skills of scholars working outside the American academy, and thereby complement, rather than replicate, the ways American Jewish Studies have been pursued in North America itself.
Just after the publication of the Theory of Communicative Action in 1981, a new generation of interpreters started a different reception of Durkheim in Germany. Hans-Peter Müller, sociologist and editor of the German translation of Leçons de sociologie, reconstructs the history of the German Durkheim’s Reception and illuminates the reasons for his interest in the French sociologist. He delivers different insights into the background which permitted the post-Habermasian generation to reach a new understanding of Durkheim’s work by enlightening the scientific and political conditions from which this new sensibility emerged.
The interview offers a reconstruction of the German reception of Durkheim since the middle of the 1970s. Hans Joas, who was one of its major protagonists, discusses the backdrop that finally permitted a scholarly examination of Durkheim’s sociology in Germany. Focussing on his personal reception Joas then gives an account of the Durkheimian themes that inspire his work.
New data from the LEADER trial show that the glucagon-like peptide 1 receptor agonist liraglutide protects against diabetic nephropathy in patients with type 2 diabetes mellitus. The renoprotective efficacy of liraglutide is not, however, as great as that reported for the sodium-glucose cotransporter 2 inhibitor emplagiflozin in the EMPA-REG OUTCOME trial.
The German Enlightenment
(2017)
The term Enlightenment (or Aufklärung) remains heavily contested. Even when historians delimit the remit of the concept, assigning it to a particular historical period rather than to an intellectual or moral programme, the public resonance of the Enlightenment remains high and problematic—especially when equated in an essentialist manner with modernity or some core values of ‘the West’. This Forum has been convened to discuss recent research on the Enlightenment in Germany, different views of the term and its ideological use in public discourse outside academia (and sometimes within it).
Dielectrophoretic functionalization of nanoelectrode arrays for the detection of influenza viruses
(2017)
Influenza virus vRNPs: quantitative investigations via fluorescence
cross-correlation spectroscopy
(2017)
Direct visualization of APLP1 cell-cell adhesion platforms via fluorescence fluctuation spectroscopy
(2017)
Tailed bacteriophages specific for Gram‐negative bacteria encounter lipopolysaccharide (LPS) during the first infection steps. Yet, it is not well understood how biochemistry of these initial interactions relates to subsequent events that orchestrate phage adsorption and tail rearrangements to initiate cell entry. For many phages, long O‐antigen chains found on the LPS of smooth bacterial strains serve as essential receptor recognized by their tailspike proteins (TSP). Many TSP are depolymerases and O‐antigen cleavage was described as necessary step for subsequent orientation towards a secondary receptor. However, O‐antigen specific host attachment must not always come along with O‐antigen degradation. In this issue of Molecular Microbiology Prokhorov et al. report that coliphage G7C carries a TSP that deacetylates O‐antigen but does not degrade it, whereas rough strains or strains lacking O‐antigen acetylation remain unaffected. Bacteriophage G7C specifically functionalizes its tail by attaching the deacetylase TSP directly to a second TSP that is nonfunctional on the host's O‐antigen. This challenges the view that bacteriophages use their TSP only to clear their way to a secondary receptor. Rather, O‐antigen specific phages may employ enzymatically active TSP as a tool for irreversible LPS membrane binding to initiate subsequent infection steps.