Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials.

AimsThis analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials.Materials and methodsData from 4983 randomized patients (1940 with MetS; 1642 with diabetes excluded) were assessed in subgroups by MetS status. Efficacy data were analysed in 4 pools per study design: 2 placebo-controlled pools (1 using alirocumab 150 mg every 2 weeks [Q2W], 1 using 75/150 mg Q2W) with background statin, and 2 ezetimibe-controlled pools (both alirocumab 75/150 mg Q2W), 1 with and 1 without background statin. Alirocumab 75/150 mg indicates possible dose increase from 75 to 150 mg at Week 12 based on Week 8 LDL-C.ResultsLDL-C percentage reduction from baseline at Week 24 with alirocumab was 63.9% (MetS) and 56.8% (non-MetS) in the pool of alirocumab 150 mg Q2W, and 42.2% to 52.2% (MetS) and 45.0% to 52.6% (non-MetS) in 3 pools using 75/150 mg Q2W. Levels of other lipid and lipoprotein parameters were also improved with alirocumab treatment, including apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein(a) and HDL-C. Overall, the percentage change at Week 24 in LDL-C and other lipids and lipoproteins did not vary by MetS status. Adverse event rates were generally similar between treatment groups, regardless of MetS status; injection-site reactions occurred more frequently in alirocumab vs control groups.ConclusionsAcross study pools, alirocumab-associated reductions in LDL-C, apolipoprotein B, and non-HDL-C were significant vs control, and did not vary by MetS status

Scale Factor Determination for the GRACE-Follow On Laser Ranging Interferometer including Thermal Coupling

The GRACE Follow-On satellites carry the very first inter-spacecraft Laser Ranging Interferometer (LRI). After more than four years in orbit, the LRI outperforms the sensitivity of the conventional Microwave Instrument (MWI). However, in the current data processing scheme, the LRI product still needs the MWI data to determine the unknown absolute laser frequency, representing the ruler for converting the raw phase measurements into a physical displacement in meters. In this paper, we derive formulas for precisely performing that conversion from the phase measurement into a range, accounting for a varying carrier frequency. Furthermore, the dominant errors due to knowledge uncertainty of the carrier frequency as well as uncorrected time biases are derived. In the second part, we address the dependency of the LRI on the MWI in the currently employed cross-calibration scheme and present three different models for the LRI laser frequency, two of which are largely independent of the MWI. Furthermore, we analyze the contribution of thermal variations on the scale factor estimates and the LRI-MWI residuals. A linear model called Thermal Coupling (TC) is derived that significantly reduces the differences between LRI and MWI to a level where the MWI observations limit the comparison.Comment: 26 pages, 15 figure

Habitus und Resonanz: eine weltbeziehungstheoretische Perspektive auf die Inkorporierung sozialweltlicher Strukturen

Die Untersuchung macht es sich zur Aufgabe, die Sozialtheorie Pierre Bourdieus und sein Konzept des Habitus um wesentliche Elemente der Weltbeziehungstheorie Hartmut Rosas und insbesondere dessen Idee der Resonanz zu erweitern. Das zentrale Anliegen ist hierbei, durch die Erhellung der Wechselwirkungen zwischen Habitus und Resonanz zu einem umfassenderen theoretischen Verständnis der individuellen Sozialisation sowie damit verbundener Problemfelder, wie Entfremdung oder die Reproduktion gesellschaftlicher Machtverhältnisse, zu gelangen. Dafür werden zunächst die grundlegenden Konzepte und Begriffe beider Theorien vorgestellt und dabei vor allem der Körper als zentraler Bezugspunkt sozialer Prägungsprozesse thematisiert. Um die Inkorporierung sozialweltlicher Strukturen durch Resonanzprozesse analytisch nachvollziehbar zu machen, wird anschließend das Körperverständnis Bourdieus um die leibsoziologischen Überlegungen Ulle Jägers erweitert und damit eine Theorie der doppelseitigen Inkorporierung (leiblich wie körperlich) vorgeschlagen. Anhand dieser theoretischen Basis wird dann der empirische Vorgang der Habitusbildung in seinen Grundzügen nachvollzogen und weltbeziehungstheoretisch erschlossen, womit einerseits der Ansatz Bourdieus um eine subjektsoziologisch fundierte Sozialisationstheorie erweitert und andererseits ein gesellschaftsstruktureller Rahmen für die Weltbeziehungssoziologie Rosas vorgeschlagen wird. Nicht zuletzt werden hieraus auch Impulse für weiterführende ungleichheitssoziologische und entfremdungskritische Betrachtungen gezogen

Discrimination between Gaussian process models: active learning and static constructions

The paper covers the design and analysis of experiments to discriminate between two Gaussian process models with different covariance kernels, such as those widely used in computer experiments, kriging, sensor location and machine learning. Two frameworks are considered. First, we study sequential constructions, where successive design (observation) points are selected, either as additional points to an existing design or from the beginning of observation. The selection relies on the maximisation of the difference between the symmetric Kullback Leibler divergences for the two models, which depends on the observations, or on the mean squared error of both models, which does not. Then, we consider static criteria, such as the familiar log-likelihood ratios and the Fréchet distance between the covariance functions of the two models. Other distance-based criteria, simpler to compute than previous ones, are also introduced, for which, considering the framework of approximate design, a necessary condition for the optimality of a design measure is provided. The paper includes a study of the mathematical links between different criteria and numerical illustrations are provided

Optimized Herschel/PACS photometer observing and data reduction strategies for moving solar system targets

The "TNOs are Cool!: A survey of the trans-Neptunian region" is a Herschel Open Time Key Program that aims to characterize planetary bodies at the outskirts of the Solar System using PACS and SPIRE data, mostly taken as scan-maps. In this paper we summarize our PACS data reduction scheme that uses a modified version of the standard pipeline for basic data reduction, optimized for faint, moving targets. Due to the low flux density of our targets the observations are confusion noise limited or at least often affected by bright nearby background sources at 100 and 160\,$\mu$m. To overcome these problems we developed techniques to characterize and eliminate the background at the positions of our targets and a background matching technique to compensate for pointing errors. We derive a variety of maps as science data products that are used depending on the source flux and background levels and the scientific purpose. Our techniques are also applicable to a wealth of other Herschel solar system photometric observations, e.g. comets and near-Earth asteroids. The principles of our observing strategies and reduction techniques for moving targets will also be applicable for similar surveys of future infrared space projects.Comment: Accepted for publication in Experimental Astronom

To defend or to attack? Antagonistic interactions between Serratia plymuthica and fungal plant pathogens, a species-specific volatile dialogue

Volatile organic compounds (VOCs) are involved in microbial interspecies communication and in the mode of action of various antagonistic interactions. They are important for balancing host-microbe interactions and provide the basis for developing biological control strategies to control plant pathogens. We studied the interactions between the bacterial antagonist Serratia plymuthica HRO-C48 and three fungal plant pathogens Rhizoctonia solani, Leptosphaeria maculans and Verticillium longisporum. Significant differences in fungal growth inhibition by the Serratia-emitted VOCs in pairwise dual culture assays and changes in the transcriptome of the bacterium and in the volatilomes of both interacting partners were observed. Even though the rate of fungal growth inhibition by Serratia was variable, the confrontation of the bacterium with the VOCs of all three fungi changed the levels of expression of the genes involved in stress response, biofilm formation, and the production of antimicrobial VOCs. Pairwise interacting microorganisms switched between defense (downregulation of gene expression) and attack (upregulation of gene expression and metabolism followed by growth inhibition of the interacting partner) modes, subject to the combinations of microorganisms that were interacting. In the attack mode HRO-C48 significantly inhibited the growth of R. solani while simultaneously boosting its own metabolism; by contrast, its metabolism was downregulated when HRO-C48 went into a defense mode that was induced by the L. maculans and V. longisporum VOCs. L. maculans growth was slightly reduced by the one bacterial VOC methyl acetate that induced a strong downregulation of expression of genes involved in almost all metabolic functions in S. plymuthica. Similarly, the interaction between S. plymuthica and V. longisporum resulted in an insignificant growth reduction of the fungus and repressed the rate of bacterial metabolism on the transcriptional level, accompanied by an intense volatile dialogue. Overall, our results indicate that VOCs substantially contribute to the highly break species-specific interactions between pathogens and their natural antagonists and thus deserving of increased consideration for pathogen control