Loop Quantum Cosmology: A Status Report

The goal of this article is to provide an overview of the current state of the art in loop quantum cosmology for three sets of audiences: young researchers interested in entering this area; the quantum gravity community in general; and, cosmologists who wish to apply loop quantum cosmology to probe modifications in the standard paradigm of the early universe. An effort has been made to streamline the material so that, as described at the end of section I, each of these communities can read only the sections they are most interested in, without a loss of continuity.Comment: 138 pages, 15 figures. Invited Topical Review, To appear in Classical and Quantum Gravity. Typos corrected, clarifications and references adde

Protocol to isolate and culture primary mouse feto-placental endothelial cells.

In the mouse, feto-placental endothelial cells (FPEC) line the inner surface of the feto-placental blood vessels located within placental labyrinthine zone and play critical roles in placental development and function. Here, we present a detailed protocol for isolation and culture of primary mouse FPEC, as well as two complementary methods (immunohistochemistry staining and flow cytometry analysis) to assess their purity. These cells are suitable for downstream ex vivo studies to investigate their functional properties, both in normal and pathological contexts. For complete details on the use and execution of this protocol, please refer to Sandovici et al. (2022)

Grasping Virtual Objects Benefits Lower Aptitude Learners’ Acquisition of Foreign Language Vocabulary

Acknowledgements Special thanks go to the Ars Electronica Centre, Linz, and to co-workers who aided in the study implementation, particularly Christoph Kremer, Erika Mondria, and the staff of the Future Lab. Supported by the Johannes Kepler Open Access Publishing Fund. Funding Open access funding provided by Johannes Kepler University Linz.Peer reviewedPublisher PD

Microstructure-sensitive fatigue modelling of medical-grade fine wire

This work presents a modelling methodology to assess the sensitivity to microstructure in high‐cycle fatigue performance of fine wires made from MP35N alloy (35Ni‐35Co‐20Cr‐10Mo in wt%) used as conductors in cardiac leads. The model consists of a microstructure generator that creates a mesh of a statistically representative microstructure, a finite element analysis using a crystal plasticity constitutive model to determine the local response behaviour of the microstructure, and a postprocesser using fatigue indicating parameters to assess the likelihood of fatigue crack initiation. The fatigue crack initiation potency for selected microstructure attributes, boundary and interface conditions, and loading profiles is determined by computing the Fatemi‐Socie fatigue indicating parameter over a physically relevant volume of scale. Case studies are used to investigate (1) the influence of nonmetallic inclusion proximity to the wire surface on fatigue potency and (2) the transition life demarcating lives primarily controlled by fatigue crack initiation versus microcrack fatigue growth

Eros, Beauty, and Phon-Aesthetic Judgements of Language Sound. We Like It Flat and Fast, but Not Melodious. Comparing Phonetic and Acoustic Features of 16 European Languages

This paper concerns sound aesthetic preferences for European foreign languages. We investigated the phonetic-acoustic dimension of the linguistic aesthetic pleasure to describe the “music” found in European languages. The Romance languages, French, Italian, and Spanish, take a lead when people talk about melodious language – the music-like effects in the language (a.k.a., phonetic chill). On the other end of the melodiousness spectrum are German and Arabic that are often considered sounding harsh and un-attractive. Despite the public interest, limited research has been conducted on the topic of phonaesthetics, i.e., the subfield of phonetics that is concerned with the aesthetic properties of speech sounds (Crystal, 2008). Our goal is to fill the existing research gap by identifying the acoustic features that drive the auditory perception of language sound beauty. What is so music-like in the language that makes people say “it is music in my ears”? We had 45 central European participants listening to 16 auditorily presented European languages and rating each language in terms of 22 binary characteristics (e.g., beautiful – ugly, funny - boring) plus indicating their language familiarities, L2 backgrounds, speaker voice liking, demographics and musicality levels. Findings revealed that all factors in complex interplay explain a certain percentage of variance: familiarity and expertise in foreign languages, speaker voice characteristics, phonetic complexity, musical acoustic properties, and finally musical expertise of the listener. The most important discovery was the trade-off between speech tempo and so-called linguistic melody (pitch variance): the faster the language, the flatter/more atonal it is in terms of the pitch (speech melody), making it highly appealing acoustically (sounding beautiful and sexy), but not so melodious in a “musical” sense

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

The EU’s Indo-Pacific strategy: prospects for cooperation with South Korea

Security and Global Affair

Dietary Fat Interacts with PCBs to Induce Changes in Lipid Metabolism in Mice Deficient in Low-Density Lipoprotein Receptor

There is evidence that dietary fat can modify the cytotoxicity of polychlorinated biphenyls (PCBs) and that coplanar PCBs can induce inflammatory processes critical in the pathology of vascular diseases. To test the hypothesis that the interaction of PCBs with dietary fat is dependent on the type of fat, low-density lipoprotein receptor–deficient (LDL-R(−/−)) mice were fed diets enriched with either olive oil or corn oil for 4 weeks. Half of the animals from each group were injected with PCB-77. Vascular cell adhesion molecule-1 (VCAM-1) expression in aortic arches was non-detectable in the olive-oil–fed mice but was highly expressed in the presence of PCB-77. PCB treatment increased liver neutral lipids and decreased serum fatty acid levels only in mice fed the corn-oil–enriched diet. PCB treatment increased mRNA expression of genes involved in inflammation, apoptosis, and oxidative stress in all mice. Upon PCB treatment, mice in both olive- and corn-oil–diet groups showed induction of genes involved in fatty acid degradation but with up-regulation of different key enzymes. Genes involved in fatty acid synthesis were reduced only upon PCB treatment in corn-oil–fed mice, whereas lipid transport/export genes were altered in olive-oil–fed mice. These data suggest that dietary fat can modify changes in lipid metabolism induced by PCBs in serum and tissues. These findings have implications for understanding the interactions of nutrients with environmental contaminants on the pathology of inflammatory diseases such as atherosclerosis

Possible Contexts of Use for in Silico Trials Methodologies: A Consensus-Based Review

The term 'In Silico Trial' indicates the use of computer modelling and simulation to evaluate the safety and efficacy of a medical product, whether a drug, a medical device, a diagnostic product or an advanced therapy medicinal product. Predictive models are positioned as new methodologies for the development and the regulatory evaluation of medical products. New methodologies are qualified by regulators such as FDA and EMA through formal processes, where a first step is the definition of the Context of Use (CoU), which is a concise description of how the new methodology is intended to be used in the development and regulatory assessment process. As In Silico Trials are a disruptively innovative class of new methodologies, it is important to have a list of possible CoUs highlighting potential applications for the development of the relative regulatory science. This review paper presents the result of a consensus process that took place in the InSilicoWorld Community of Practice, an online forum for experts in in silico medicine. The experts involved identified 46 descriptions of possible CoUs which were organised into a candidate taxonomy of nine CoU categories. Examples of 31 CoUs were identified in the available literature; the remaining 15 should, for now, be considered speculative