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Gilbert et al. conclude that evidence from the Open Science Collaboration’s Reproducibility Project: Psychology indicates high reproducibility, given the study methodology. Their very optimistic assessment is limited by statistical misconceptions and by causal inferences from selectively interpreted, correlational data. Using the Reproducibility Project: Psychology data, both optimistic and pessimistic conclusions about reproducibility are possible, and neither are yet warranted.
The Research Data Policy of the University of Potsdam has been ratified by Senate on September 25, 2019 and published in Amtliche Bekanntmachungen “Official Notices” September 30, 2019. It applies to all researchers and research support staff.
The Recommendations for the Handling of Research Data at the University of Potsdam specify and complement the Research Data Policy of the University of Potsdam. They are aimed at all researchers and research support staff have been adopted by Senate’s Commission for Research and Junior Academics (FNK) on on October 9, 2019.
This record provides a non-official translation of both documents from the German original.
Reply to Peng et al.: Archaeological contexts should not be ignored for early chicken domestication
(2015)
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.
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 bibliographic project 'Renaissance Linguistics Archive' (R.L.A.) aimed at establishing a comprehensive database of secondary sources covering the linguistics ideas developed by Renaissance scholars in Europe. The database project, founded in 1986 by Mirko Tavoni (Pisa) and in 1994 transferred to Gerda Haßler (Potsdam), resulted so far in three print-outs, each of them counting 1000 records. It is the aim of this website to publish the results of the collective efforts undertaken thus far (R.L.A. 1.0, 1986-1999).
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.
This paper proposes an education approach for master and bachelor students to enhance their skills in the area of reliability, safety and security of the electronic components in automated driving. The approach is based on the active synergetic work of research institutes, academia and industry in the frame of joint lab. As an example, the jointly organized summer school with the respective focus is organized and elaborated.
Reinhard Hujer
(2020)
This paper focuses on the characterization and use of polymer-modified phosphatidylcholine (PC)/sodium dodecyl sulfate (SDS)-based inverse microemulsions as a template phase for BaSO4 nanoparticle formation. The area of the optically clear inverse microemulsion phase in the isooctane/hexanol/water/PC/SDS system is not significantly changed by adding polyelectrolytes, i.e., poly(diallyldimethylammonium chloride) (PDADMAC), or amphoteric copolymers of diallyldimethylammonium chloride and maleamid acid to the SDS-modified inverse microemulsion. Shear experiments show non- Newtonian flow behavior and oscillation experiments show a frequency-dependent viscosity increase (dilatant behavior) of the microemulsions. Small amounts of bulk water were identified by means of differential scanning calorimetry. One can conclude that the macromolecules are incorporated into the individual droplets, and polymer-filled microemulsions are formed. The polymer-filled microemulsions were used as a template phase for the synthesis of BaSO4 nanoparticles. After solvent evaporation the nanoparticles were redispersed in water and isooctane, respectively. The polymers incorporated into the microemulsion are involved in the redispersion process and influence the size and shape of the redispersed BaSO4 particles in a specific way. The crystallization process mainly depends on the type of solvent and the polymer component added. In the presence of the cationic polyelectrolyte PDADMAC the crystallization to larger cubic crystals is inhibited, and layers consisting of polymer-stabilized spherical nanoparticles of BaSO4 (6 nm in size) will be observed. (c) 2004 Elsevier Inc. All rights reserved
Various techniques are utilized by the seismological community, extractive industries, energy and geoengineering companies to identify earthquake nucleation processes in close proximity to engineering operation points. These operations may comprise fluid extraction or injections, artificial water reservoir impoundments, open pit and deep mining, deep geothermal power generations or carbon sequestration. In this letter to the editor, we outline several lines of investigation that we suggest to follow to address the discrimination problem between natural seismicity and seismic events induced or triggered by geoengineering activities. These suggestions have been developed by a group of experts during several meetings and workshops, and we feel that their publication as a summary report is helpful for the geoscientific community. Specific investigation procedures and discrimination approaches, on which our recommendations are based, are also published in this Special Issue (SI) of Journal of Seismology.
Recht im Ausnahmezustand
(2020)
Viele Länder weltweit haben im Bemühen, die Ausbreitung des Corona-Virus zu stoppen oder wenigstens zu verlangsamen, drastische Maßnahmen ergriffen: Schulen, Universitäten und kulturelle Einrichtungen sind geschlossen, öffentliche Plätze dürfen nicht betreten und das Zuhause nur in dringenden Fällen verlassen werden. Damit schränken einige der Maßnahmen sogar fundamentale Menschenrechte ein. Matthias Zimmermann sprach mit Prof. Dr. Andreas Zimmermann, dem Direktor des Potsdamer MenschenRechtsZentrums (MRZ), und Prof. Dr. Norman Weiß, der seit vielen Jahren am MRZ tätig ist, über die Menschenrechte im Ausnahmezustand.
A fundamental task in 3D geovisualization and GIS applications is the visualization of vector data that can represent features such as transportation networks or land use coverage. Mapping or draping vector data represented by geometric primitives (e.g., polylines or polygons) to 3D digital elevation or 3D digital terrain models is a challenging task. We present an interactive GPU-based approach that performs geometry-based draping of vector data on per-frame basis using an image-based representation of a 3D digital elevation or terrain model only.
Harmonized data file as the basis for comparative analysis of quality of life in the Candidate Countries and the European Union member states, based on seven different data sets, one Eurobarometer survey covering 13 Candidate Countries with an identical set of variables conducted in April 2002, the other six Standard Eurobarometer of different subjects and fielded in different years, each with another set of questions identical with the CC Eurobarometer. Selected aggregate indicators of quality of life ... describing the social situation in the EU15 and Candidate Countries.
The identification of vulnerabilities relies on detailed information about the target infrastructure. The gathering of the necessary information is a crucial step that requires an intensive scanning or mature expertise and knowledge about the system even though the information was already available in a different context. In this paper we propose a new method to detect vulnerabilities that reuses the existing information and eliminates the necessity of a comprehensive scan of the target system. Since our approach is able to identify vulnerabilities without the additional effort of a scan, we are able to increase the overall performance of the detection. Because of the reuse and the removal of the active testing procedures, our approach could be classified as a passive vulnerability detection. We will explain the approach and illustrate the additional possibility to increase the security awareness of users. Therefore, we applied the approach on an experimental setup and extracted security relevant information from web logs.
The globally distributed sperm whale (Physeter macrocephalus) has a partly matrilineal social structure with predominant male dispersal. At the beginning of 2016, a total of 30 male sperm whales stranded in five different countries bordering the southern North Sea. It has been postulated that these individuals were on a migration route from the north to warmer temperate and tropical waters where females live in social groups. By including samples from four countries (n = 27), this event provided a unique chance to genetically investigate the maternal relatedness and the putative origin of these temporally and spatially co-occuring male sperm whales. To utilize existing genetic resources, we sequenced 422 bp of the mitochondrial control region, a molecular marker for which sperm whale data are readily available from the entire distribution range. Based on four single nucleotide polymorphisms (SNPs) within the mitochondrial control region, five matrilines could be distinguished within the stranded specimens, four of which matched published haplotypes previously described in the Atlantic. Among these male sperm whales, multiple matrilineal lineages co-occur. We analyzed the population differentiation and could show that the genetic diversity of these male sperm whales is comparable to the genetic diversity in sperm whales from the entire Atlantic Ocean. We confirm that within this stranding event, males do not comprise maternally related individuals and apparently include assemblages of individuals from different geographic regions. (c) 2017 Deutsche Gesellschaft fur Saugetierkunde. Published by Elsevier GmbH. All rights reserved.
Public Private Partnerships as an Accelerator of Broadband Diffusion? Findings from Case Studies,
(2006)
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.
Oxidative posttranslationale Modifikationen endogener Proteine werden v. a. durch reaktive Sauerstoff- und Stickstoffspezies (engl:. Reactive Oxygen Species, ROS, reactive nitrogen species, RNS) hervorgerufen und können sowohl reversibel (z. B. Disulfidbindungen) als auch irreversibel (z. B. Proteincarbonyle) erfolgen [1–3]. Lange wurde angenommen, dass oxidative posttranslationale Proteinmodifikationen (oxPTPM) nur von untergeordneter Bedeutung für den Metabolismus sind. Tatsächlich handelt es sich jedoch um einen physiologischen Prozess, der über die Modulation der Proteinstruktur auch die Proteinfunktion (z. B. Enzymaktivität, Stabilität) und somit zahlreiche Stoffwechselwege wie den Energiestoffwechsel, die Immunfunktion, die vaskuläre Funktion sowie Apoptose und Genexpression beeinflussen kann. Die Bildung von oxPTPM ist dabei hochreguliert und hängt u. a. von der Proteinstruktur, der Verfügbarkeit von ROS und RNS sowie dem lokalen Mikromilieu der Zelle ab [2, 4].
The collaboration during the modeling process is uncomfortable and characterized by various limitations. Faced with the successful transfer of first process modeling languages to the augmented world, non-transparent processes can be visualized in a more comprehensive way. With the aim to rise comfortability, speed, accuracy and manifoldness of real world process augmentations, a framework for the bidirectional interplay of the common process modeling world and the augmented world has been designed as morphologic box. Its demonstration proves the working of drawn AR integrations. Identified dimensions were derived from (1) a designed knowledge construction axiom, (2) a designed meta-model, (3) designed use cases and (4) designed directional interplay modes. Through a workshop-based survey, the so far best AR modeling configuration is identified, which can serve for benchmarks and implementations.
Prevention of Cognitive Decline: A Physical Exercise Perspective on Brain Health in the Long Run
(2016)
Declarative languages for knowledge representation and reasoning provide constructs to define preference relations over the set of possible interpretations, so that preferred models represent optimal solutions of the encoded problem. We introduce the notion of approximation for replacing preference relations with stronger preference relations, that is, relations comparing more pairs of interpretations. Our aim is to accelerate the computation of a non-empty subset of the optimal solutions by means of highly specialized algorithms. We implement our approach in Answer Set Programming (ASP), where problems involving quantitative and qualitative preference relations can be addressed by ASPRIN, implementing a generic optimization algorithm. Unlike this, chains of approximations allow us to reduce several preference relations to the preference relations associated with ASP’s native weak constraints and heuristic directives. In this way, ASPRIN can now take advantage of several highly optimized algorithms implemented by ASP solvers for computing optimal solutions
Preface to BPM 2014
(2016)
Preface
(2018)
Preface
(2019)
Preface
(2017)
Preface
(2018)
Data limitations can lead to unrealistic fits of predictive species distribution models (SDMs) and spurious extrapolation to novel environments. Here, we want to draw attention to novel combinations of environmental predictors that are within the sampled range of individual predictors but are nevertheless outside the sample space. These tend to be overlooked when visualizing model behaviour. They may be a cause of differing model transferability and environmental change predictions between methods, a problem described in some studies but generally not well understood. We here use a simple simulated data example to illustrate the problem and provide new and complementary visualization techniques to explore model behaviour and predictions to novel environments. We then apply these in a more complex real-world example. Our results underscore the necessity of scrutinizing model fits, ecological theory and environmental novelty.
Predicting macroscopic elastic rock properties requires detailed information on microstructure
(2017)
Predicting variations in macroscopic mechanical rock behaviour due to microstructural changes, driven by mineral precipitation and dissolution is necessary to couple chemo-mechanical processes in geological subsurface simulations. We apply 3D numerical homogenization models to estimate Young’s moduli for five synthetic microstructures, and successfully validate our results for comparable geometries with the analytical Mori-Tanaka approach. Further, we demonstrate that considering specific rock microstructures is of paramount importance, since calculated elastic properties may deviate by up to 230 % for the same mineral composition. Moreover, agreement between simulated and experimentally determined Young’s moduli is significantly improved, when detailed spatial information are employed.
Bottom-up saliency is often cited as a factor driving the choice of fixation locations of human observers, based on the (partial) success of saliency models to predict fixation densities in free viewing. However, these observations are only weak evidence for a causal role of bottom-up saliency in natural viewing behaviour. To test bottom-up saliency more directly, we analyse the performance of a number of saliency models---including our own saliency model based on our recently published model of early visual processing (Schütt & Wichmann, 2017, JoV)---as well as the theoretical limits for predictions over time. On free viewing data our model performs better than classical bottom-up saliency models, but worse than the current deep learning based saliency models incorporating higher-level information like knowledge about objects. However, on search data all saliency models perform worse than the optimal image independent prediction. We observe that the fixation density in free viewing is not stationary over time, but changes over the course of a trial. It starts with a pronounced central fixation bias on the first chosen fixation, which is nonetheless influenced by image content. Starting with the 2nd to 3rd fixation, the fixation density is already well predicted by later densities, but more concentrated. From there the fixation distribution broadens until it reaches a stationary distribution around the 10th fixation. Taken together these observations argue against bottom-up saliency as a mechanistic explanation for eye movement control after the initial orienting reaction in the first one to two saccades, although we confirm the predictive value of early visual representations for fixation locations. The fixation distribution is, first, not well described by any stationary density, second, is predicted better when including object information and, third, is badly predicted by any saliency model in a search task.
The problem of atmospheric emission from OH molecules is a long standing problem for near-infrared astronomy. PRAXIS is a unique spectrograph which is fed by fibres that remove the OH background and is optimised specifically to benefit from OH-Suppression. The OH suppression is achieved with fibre Bragg gratings, which were tested successfully on the GNOSIS instrument. PRAXIS uses the same fibre Bragg gratings as GNOSIS in its first implementation, and will exploit new, cheaper and more efficient, multicore fibre Bragg gratings in the second implementation. The OH lines are suppressed by a factor of similar to 1000, and the expected increase in the signal-to-noise in the interline regions compared to GNOSIS is a factor of similar to 9 with the GNOSIS gratings and a factor of similar to 17 with the new gratings. PRAXIS will enable the full exploitation of OH suppression for the first time, which was not achieved by GNOSIS (a retrofit to an existing instrument that was not OH-Suppression optimised) due to high thermal emission, low spectrograph transmission and detector noise. PRAXIS has extremely low thermal emission, through the cooling of all significantly emitting parts, including the fore-optics, the fibre Bragg gratings, a long length of fibre, and the fibre slit, and an optical design that minimises leaks of thermal emission from outside the spectrograph. PRAXIS has low detector noise through the use of a Hawaii-2RG detector, and a high throughput through a efficient VPH based spectrograph. PRAXIS will determine the absolute level of the interline continuum and enable observations of individual objects via an IFU. In this paper we give a status update and report on acceptance tests.
The fabrication of compartmented micellar systems is an exciting new area of research in the field of polymer self-assembly. Multicompartment micelles composed of a water-soluble shell and a segregated hydrophobic core can be obtained via direct aqueous self-assembly of preformed polymeric amphiphiles possessing one hydrophilic segment and two incompatible hydrophobic segments (e.g. hydrocarbon and fluorocarbon blocks). Such macromolecular building-blocks were prepared in the present work principally via reversible addition-fragmentation transfer polymerization (RAFT). Polysoaps or triblock macrosurfactants can be synthesized in high yields by RAFT under relatively straightforward experimental conditions.
Playful Classics
(2021)
In self-incompatible plants the female style rejects self pollen, yet the extent to which the female style in the many self-compatible species can still select between different pollen genotypes and thus bias fertilization success is unclear. A new study identifies the molecular basis for how styles of the self-compatible coyote tobacco bias the fertilization success of pollen genotypes using matching gene expression patterns in a manner analogous to cryptic female choice in animals.
Planstadt Doberlug
(2020)
PlAnalyzer
(2018)
In this work we propose PIAnalyzer, a novel approach to analyze PendingIntent related vulnerabilities. We empirically evaluate PIAnalyzer on a set of 1000 randomly selected applications from the Google Play Store and find 1358 insecure usages of Pendinglntents, including 70 severe vulnerabilities. We manually inspected ten reported vulnerabilities out of which nine correctly reported vulnerabilities, indicating a high precision. The evaluation shows that PIAnalyzer is efficient with an average execution time of 13 seconds per application.
Photonic sensing in highly concentrated biotechnical processes by photon density wave spectroscopy
(2017)
Photon Density Wave (PDW) spectroscopy is introduced as a new approach for photonic sensing in highly concentrated biotechnical processes. It independently quantifies the absorption and reduced scattering coefficient calibration-free and as a function of time, thus describing the optical properties in the vis/NIR range of the biomaterial during their processing. As examples of industrial relevance, enzymatic milk coagulation, beer mashing, and algae cultivation in photo bioreactors are discussed.
In a recent contribution in Nature (vol. 442, pp. 555-558) Austin & Vivanco showed that sunlight is the dominant factor for decomposition of grass litter in a semi-arid grassland in Argentine. The quantification of this effect was portrayed as a novel finding. I put this result in the context of three other publications from as early as 1980 that quantified photodegradation. My synopsis shows that photodegradation is an important process in semi-arid grasslands in South America, North America and eastern Europe.
User-generated content on social media platforms is a rich source of latent information about individual variables. Crawling and analyzing this content provides a new approach for enterprises to personalize services and put forward product recommendations. In the past few years, brands made a gradual appearance on social media platforms for advertisement, customers support and public relation purposes and by now it became a necessity throughout all branches. This online identity can be represented as a brand personality that reflects how a brand is perceived by its customers. We exploited recent research in text analysis and personality detection to build an automatic brand personality prediction model on top of the (Five-Factor Model) and (Linguistic Inquiry and Word Count) features extracted from publicly available benchmarks. The proposed model reported significant accuracy in predicting specific personality traits form brands. For evaluating our prediction results on actual brands, we crawled the Facebook API for 100k posts from the most valuable brands' pages in the USA and we visualize exemplars of comparison results and present suggestions for future directions.
Evaluating the performance of self-adaptive systems (SAS) is challenging due to their complexity and interaction with the often highly dynamic environment. In the context of self-healing systems (SHS), employing simulators has been shown to be the most dominant means for performance evaluation. Simulating a SHS also requires realistic fault injection scenarios. We study the state of the practice for evaluating the performance of SHS by means of a systematic literature review. We present the current practice and point out that a more thorough and careful treatment in evaluating the performance of SHS is required.
Speech scientists have long noted that the qualities of naturally-produced vowels do not remain constant over their durations regardless of being nominally "monophthongs" or "diphthongs". Recent acoustic corpora show that there are consistent patterns of first (F1) and second (F2) formant frequency change across different vowel categories. The three Australian English (AusE) close front vowels /i:, 1, i/ provide a striking example: while their midpoint or mean F1 and F2 frequencies are virtually identical, their spectral change patterns distinctly differ. The results indicate that, despite the distinct patterns of spectral change of AusE /i:, i, la/ in production, its perceptual relevance is not uniform, but rather vowel-category dependent.
Peace orders of modern times
(2019)
Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping on- going thought and behavior. The influence of Pavlovian stimuli on on-going behavior is paradigmatically measured by Pavlovian-to-instrumental-transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol
dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent, and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced Pavlovian-Instrumental transfer.
Methods: 32 recently detoxified alcohol-dependent patients and 32 age and gender matched healthy controls performed a PIT task with instrumental go/no-go approach behaviours. The task involved both Pavlovian stimuli associated with monetary rewards and losses, and images of drinks.
Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs.
Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol- dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
For a singularly perturbed parabolic - ODE system we construct the asymptotic expansion in the small parameter in the case, when the degenerate equation has a double root. Such systems, which are called partly dissipative reaction-diffusion systems, are used to model various natural processes, including the signal transmission along axons, solid combustion and the kinetics of some chemical reactions. It turns out that the algorithm of the construction of the boundary layer functions and the behavior of the solution in the boundary layers essentially differ from that ones in case of a simple root. The multizonal initial and boundary layers behaviour was stated.
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.
Pace-of-life syndromes
(2018)
This introduction to the topical collection on Pace-of-life syndromes: a framework for the adaptive integration of behaviour, physiology, and life history provides an overview of conceptual, theoretical, methodological, and empirical progress in research on pace-of-life syndromes (POLSs) over the last decade. The topical collection has two main goals. First, we briefly describe the history of POLS research and provide a refined definition of POLS that is applicable to various key levels of variation (genetic, individual, population, species). Second, we summarise the main lessons learned from current POLS research included in this topical collection. Based on an assessment of the current state of the theoretical foundations and the empirical support of the POLS hypothesis, we propose (i) conceptual refinements of theory, particularly with respect to the role of ecology in the evolution of (sexual dimorphism in) POLS, and (ii) methodological and statistical approaches to the study of POLS at all major levels of variation. This topical collection further holds (iii) key empirical examples demonstrating how POLS structures may be studied in wild populations of (non) human animals, and (iv) a modelling paper predicting POLS under various ecological conditions. Future POLS research will profit from the development of more explicit theoretical models and stringent empirical tests of model assumptions and predictions, increased focus on how ecology shapes (sex-specific) POLS structures at multiple hierarchical levels, and the usage of appropriate statistical tests and study designs. Significance statement As an introduction to the topical collection, we summarise current conceptual, theoretical, methodological and empirical progress in research on pace-of-life syndromes (POLSs), a framework for the adaptive integration of behaviour, physiology and life history at multiple hierarchical levels of variation (genetic, individual, population, species). Mixed empirical support of POLSs, particularly at the within-species level, calls for an evaluation and refinement of the hypothesis. We provide a refined definition of POLSs facilitating testable predictions. Future research on POLSs will profit from the development of more explicit theoretical models and stringent empirical tests of model assumptions and predictions, increased focus on how ecology shapes (sex-specific) POLSs structures at multiple hierarchical levels and the usage of appropriate statistical tests and study designs.
Background: Infliximab (IFX), an anti-TNF monoclonal antibody approved for the treatment of inflammatory bowel disease, is dosed per kg body weight (BW). However, the rationale for body size adjustment has not been unequivocally demonstrated [1], and first attempts to improve IFX therapy have been undertaken [2]. The aim of our study was to assess the impact of different dosing strategies (i.e. body size-adjusted and fixed dosing) on drug exposure and pharmacokinetic (PK) target attainment. For this purpose, a comprehensive simulation study was performed, using patient characteristics (n=116) from an in-house clinical database.
Methods: IFX concentration-time profiles of 1000 virtual, clinically representative patients were generated using a previously published PK model for IFX in patients with Crohn's disease [3]. For each patient 1000 profiles accounting for PK variability were considered. The IFX exposure during maintenance treatment after the following dosing strategies was compared: i) fixed dose, and per ii) BW, iii) lean BW (LBW), iv) body surface area (BSA), v) height (HT), vi) body mass index (BMI) and vii) fat-free mass (FFM)). For each dosing strategy the variability in maximum concentration Cmax, minimum concentration Cmin (= C8weeks) and area under the concentration-time curve (AUC), as well as percent of patients achieving the PK target, Cmin=3 μg/mL [4] were assessed.
Results: For all dosing strategies the variability of Cmin (CV ≈110%) was highest, compared to Cmax and AUC, and was of similar extent regardless of dosing strategy. The proportion of patients reaching the PK target (≈⅓ was approximately equal for all dosing strategies.
Our Conclusions
(2018)
Data analytics are moving beyond the limits of a single data processing platform. A cross-platform query optimizer is necessary to enable applications to run their tasks over multiple platforms efficiently and in a platform-agnostic manner. For the optimizer to be effective, it must consider data movement costs across different data processing platforms. In this paper, we present the graph-based data movement strategy used by RHEEM, our open-source cross-platform system. In particular, we (i) model the data movement problem as a new graph problem, which we prove to be NP-hard, and (ii) propose a novel graph exploration algorithm, which allows RHEEM to discover multiple hidden opportunities for cross-platform data processing.