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Increased aortic stiffness is known to be associated with atherosclerosis and has a predictive value for cardiovascular events. This study aims to investigate the local distribution of early arterial stiffening due to initial atherosclerotic lesions. Therefore, global and local pulse wave velocity (PWV) were measured in ApoE\(^{-/-}\) and wild type (WT) mice using ultrahigh field MRI. For quantification of global aortic stiffness, a new multi-point transit-time (TT) method was implemented and validated to determine the global PWV in the murine aorta. Local aortic stiffness was measured by assessing the local PWV in the upper abdominal aorta, using the flow/area (QA) method. Significant differences between age matched ApoE\(^{-/-}\) and WT mice were determined for global and local PWV measurements (global PWV: ApoE\(^{-/-}\): 2.7 ±0.2m/s vs WT: 2.1±0.2m/s, P<0.03; local PWV: ApoE\(^{-/-}\): 2.9±0.2m/s vs WT: 2.2±0.2m/s, P<0.03). Within the WT mouse group, the global PWV correlated well with the local PWV in the upper abdominal aorta (R\(^2\) = 0.75, P<0.01), implying a widely uniform arterial elasticity.
In ApoE\(^{-/-}\) animals, however, no significant correlation between individual local and global PWV was present (R\(^2\) = 0.07, P = 0.53), implying a heterogeneous distribution of vascular stiffening in early atherosclerosis. The assessment of global PWV using the new multi-point TT measurement technique was validated against a pressure wire measurement in a vessel
phantom and showed excellent agreement. The experimental results demonstrate that vascular stiffening caused by early atherosclerosis is unequally distributed over the length of large vessels. This finding implies that assessing heterogeneity of arterial stiffness by multiple local measurements of PWV might be more sensitive than global PWV to identify early atherosclerotic lesions.
Introduction: Calciphylaxis/calcific uremic arteriolopathy affects mainly end-stage kidney disease patients but is also associated with malignant disorders such as myeloma, melanoma and breast cancer. Genetic risk factors of calciphylaxis have never been studied before.
Methods: We investigated 10 target genes using a tagging SNP approach: the genes encoding CD73/ ecto-5'-nucleotidase (purinergic pathway), Matrix Gla protein, Fetuin A, Bone Gla protein, VKORC1 (all related to intrinsic calcification inhibition), calcium-sensing receptor, FGF23, Klotho, vitamin D receptor, stanniocalcin 1 (all related to CKD-MBD). 144 dialysis patients from the German calciphylaxis registry were compared with 370 dialysis patients without history of CUA. Genotyping was performed using iPLEX Gold MassARRAY(Sequenom, San Diego, USA), KASP genotyping chemistry (LGC, Teddington, Middlesex, UK) or sequencing. Statistical analysis comprised logistic regression analysis with adjustment for age and sex.
Results: 165 SNPs were finally analyzed and 6 SNPs were associated with higher probability for calciphylaxis (OR>1) in our cohort. Nine SNPs of three genes (CD73, FGF23 and Vitamin D receptor) reached nominal significance (p< 0.05), but did not reach statistical significance after correction for multiple testing. Of the CD73 gene, rs4431401 (OR = 1.71, 95%CI 1.08-2.17, p = 0.023) and rs9444348 (OR = 1.48, 95% CI 1.11-1.97, p = 0.008) were associated with a higher probability for CUA. Of the FGF23 and VDR genes, rs7310492, rs11063118, rs13312747 and rs17882106 were associated with a higher probability for CUA.
Conclusion: Polymorphisms in the genes encoding CD73, vitamin D receptor and FGF23 may play a role in calciphylaxis development. Although our study is the largest genetic study on calciphylaxis, it is limited by the low sample sizes. It therefore requires replication in other cohorts if available.
Objective: Perception of time as well as rhythm in musical structures rely on complex brain mechanisms and require an extended network of multiple neural sources. They are therefore sensitive to impairment. Several psychophysical studies have shown that patients with Parkinson's disease (PD) have deficits in perceiving time and rhythms due to a malfunction of the basal ganglia (BG) network.
Method: In this study we investigated the time perception of PD patients during music perception by assessing their just noticeable difference (JND) in the time perception of a complex musical Gestalt. We applied a temporal discrimination task using a short melody with a clear beat-based rhythm. Among the subjects, 26 patients under L-Dopa administration and 21 age-matched controls had to detect an artificially delayed time interval in the range between 80 and 300 ms in the middle of the musical period. We analyzed the data by (a) calculating the detection threshold directly, (b) by extrapolating the JNDs, (c) relating it to musical expertise.
Results: Patients differed from controls in the detection of time-intervals between 220 and 300 ms (*p = 0.0200, n = 47). Furthermore, this deficit depended on the severity of the disease (*p = 0.0452; n = 47). Surprisingly, PD patients did not show any deficit of their JND compared to healthy controls, although the results showed a trend (*p = 0.0565, n = 40). Furthermore, no significant difference of the JND was found according to the severity of the disease. Additionally, musically trained persons seemed to have lower thresholds in detecting deviations in time and syntactic structures of music (*p = 0.0343, n = 39).
Conclusion: As an explanation of these results, we would like to propose the hypothesis of a time-syntax-congruency in music perception suggesting that processing of time and rhythm is a Gestalt process and that cortical areas involved in processing of musical syntax may compensate for impaired BG circuits that are responsible for time processing and rhythm perception. This mechanism may emerge more strongly as the deficits in time processing and rhythm perception progress. Furthermore, we presume that top-down-bottom-up-processes interfere additionally and interact in this context of compensation.
In this article, we present approaches to interactive simulations of biohybrid systems. These simulations are comprised of two major computational components: (1) agent-based developmental models that retrace organismal growth and unfolding of technical scaffoldings and (2) interfaces to explore these models interactively. Simulations of biohybrid systems allow us to fast forward and experience their evolution over time based on our design decisions involving the choice, configuration and initial states of the deployed biological and robotic actors as well as their interplay with the environment. We briefly introduce the concept of swarm grammars, an agent-based extension of L-systems for retracing growth processes and structural artifacts. Next, we review an early augmented reality prototype for designing and projecting biohybrid system simulations into real space. In addition to models that retrace plant behaviors, we specify swarm grammar agents to braid structures in a self-organizing manner. Based on this model, both robotic and plant-driven braiding processes can be experienced and explored in virtual worlds. We present an according user interface for use in virtual reality. As we present interactive models concerning rather diverse description levels, we only ensured their principal capacity for interaction but did not consider efficiency analyzes beyond prototypic operation. We conclude this article with an outlook on future works on melding reality and virtuality to drive the design and deployment of biohybrid systems.
This essay argues that Orwell’s representation of animals as companion species offers a strikingly new, as-yet largely neglected view of animal agency and interiority in his work. In “Shooting an Elephant”, Burmese Days and “Marrakech”, the writer’s focus on the social reject is supplemented by a marked sense of community implying human tragedy yet framing it within precariously situated human-animal, colonial or urban-imperial transitions that visualise animals as agents of change and co-shaping species interdependent with the lives of the humans that utilize and domineer them. Animals are required whenever Orwell aspires to shift from isolation to communality, from the self-conscious outsider to the larger realm of ideas framing the world in which his characters strive to overstep the accepted lines of social performance and conformity. Read in and around disciplinary structures of rationalization, Orwell’s animals appear to secure themselves, quite paradoxically, a place within the normative anthropocentric framework excluding them. They extend beyond anthropomorphising or allegorical modes of description and open up bio-political perspectives within and across regimes of knowledge and empathy. Orwell’s writings thus present a challenge to the culturally accredited fantasy of human exceptionalism, collapsing any epistemic space between humans and animals and burying the idea of sustaining radical species distinction.
Für Menschen ohne Religionszugehörigkeit und religiöses Selbstverständnis liegt kaum eine Beschreibung jenseits negativer Abgrenzungen von traditioneller Religion vor, wie sie in den Begriffen „nichtreligiös“ und „konfessionslos“ zum Ausdruck kommen. Der Aufsatz untersucht die Option eines säkularen „worldview“ und fragt, ob und in welchem Maß religiöse und nichtreligiöse Studienteilnehmer sich in ihrer Haltung zu Menschenrechten unterscheiden. Die empirische Studie (N=2244) zeigt, dass Menschenrechte bei jungen Menschen bei unterschiedlichen Akzentsetzungen durchweg auf Zustimmung stoßen. In Umrissen tritt dabei ein gemeinsamer „worldview“ oder eine „Weltanschauung“ der säkularen Befragten hervor, die in der Anerkennung des intrinsischen Wertes des Anderen und gesellschaftlich gesetzter Normen besteht.
Schule als Lern- und Lebensort zukünftiger Generationen partizipiert an global sich vollziehenden medialen Transformationsprozessen. Religionspädagogik und -didaktik sind, wie alle anderen Fachwissenschaften auch, herausgefordert, die Integration digitaler Medien in Theorie und Praxis zu reflektieren und konzeptionieren. Dies hat in mindestens drei Dimensionen zu erfolgen: beim Lernen mit digitalen Medien, beim Lernen über digitale Medien sowie in der Einübung in eine konstruktiv-kritische Medienbildung. Das Projekt ist der Entwicklung, Erprobung und Evaluation von Lernszenarien im Religionsunterricht und im Austausch mit außerschulischen religiösen Bildungsorten gewidmet.