Elevated Levels of Toxic Bile Acids in Serum of Cystic Fibrosis Patients with CFTR Mutations Causing Pancreatic Insufficiency

Hepatobiliary involvement is a hallmark in cystic fibrosis (CF), as the causative CF Transmembrane Conductance Regulator (CFTR) defect is expressed in the biliary tree. However, bile acid (BA) compositions in regard to pancreatic insufficiency, which is present at an early stage in about 85% of CF patients, have not been satisfactorily understood. We assess the pattern of serum BAs in people with CF (pwCF) without CFTR modulator therapy in regard to pancreatic insufficiency and the CFTR genotype. In 47 pwCF, 10 free and 12 taurine- and glycine-conjugated BAs in serum were prospectively assessed. Findings were related to genotype, pancreatic insufficiency prevalence (PIP)-score, and hepatic involvement indicated by serum liver enzymes, as well as clinical and ultrasound criteria for CF-related liver disease. Serum concentrations of total primary BAs and free cholic acid (CA) were significantly higher in pwCF with higher PIP-scores (p = 0.025, p = 0.009, respectively). Higher total BAs were seen in pwCF with PIP-scores ≥0.88 (p = 0.033) and with pancreatic insufficiency (p = 0.034). Free CA was higher in patients with CF-related liver involvement without cirrhosis, compared to pwCF without liver disease (2.3-fold, p = 0.036). pwCF with severe CFTR genotypes, as assessed by the PIP-score, reveals more toxic BA compositions in serum. Subsequent studies assessing changes in BA homeostasis during new highly effective CFTR-modulating therapies are of high interest.     

Single-Cell RNA Sequencing Reveals Heterogeneity and Functional Diversity of Lymphatic Endothelial Cells

Lymphatic endothelial cells (LECs) line the lymphatic vasculature and play a central role in the immune response. LECs have abilities to regulate immune transport, to promote immune cell survival, and to cross present antigens to dendritic cells. Single-cell RNA sequencing (scRNA) technology has accelerated new discoveries in the field of lymphatic vascular biology. This review will summarize these new findings in regard to embryonic development, LEC heterogeneity with associated functional diversity, and interactions with other cells. Depending on the organ, location in the lymphatic vascular tree, and micro-environmental conditions, LECs feature unique properties and tasks. Furthermore, adjacent stromal cells need the support of LECs for fulfilling their tasks in the immune response, such as immune cell transport and antigen presentation. Although aberrant lymphatic vasculature has been observed in a number of chronic inflammatory diseases, the knowledge on LEC heterogeneity and functional diversity in these diseases is limited. Combining scRNA sequencing data with imaging and more in-depth functional experiments will advance our knowledge of LECs in health and disease. Building the case, the LEC could be put forward as a new therapeutic target in chronic inflammatory diseases, counterweighting the current immune-cell focused therapies.     

The Stratosphere platform for big data analytics

We present Stratosphere, an open-source software stack for parallel data analysis. Stratosphere brings together a unique set of features that allow the expressive, easy, and efficient programming of analytical applications at very large scale. Stratosphere’s features include “in situ” data processing, a declarative query language, treatment of user-defined functions as first-class citizens, automatic program parallelization and optimization, support for iterative programs, and a scalable and efficient execution engine. Stratosphere covers a variety of “Big Data” use cases, such as data warehousing, information extraction and integration, data cleansing, graph analysis, and statistical analysis applications. In this paper, we present the overall system architecture design decisions, introduce Stratosphere through example queries, and then dive into the internal workings of the system’s components that relate to extensibility, programming model, optimization, and query execution. We experimentally compare Stratosphere against popular open-source alternatives, and we conclude with a research outlook for the next years.     

Long-Term Orientation and Relationship Lending: A Cross-Cultural Study on the Effect of Time Preferences on the Choice of Corporate Debt

We examine how time preferences impact the financing decision of firms. We hypothesize that the degree of long-term orientation in a country is positively related to the use of bank relationship lending. Based on a thorough theoretical investigation and an extensive empirical analysis using a large, worldwide dataset, we find strong support for our hypothesis on the role of time preferences for financial intermediation. Our results are robust to controlling for other determinants of the choice of debt financing as well as to applying alternative variables and different estimation methods. Firms in long-term orientation countries appear to prefer relationship bank financing, since it is usually available for the long run and will not be withdrawn quickly in response to adverse developments. This allows managers to preserve a more strategic view and pursue longer planning horizons.     

7 Themes for guiding situated ergonomic assessments of medical devices: A case study of an inpatient glucometer

There is relatively little guidance on the situated ergonomic assessment of medical devices, and few case studies that detail this type of evaluation. This paper reports results of a detailed case study that focuses on the design and use of a modern blood glucose meter on an oncology ward. We spent approximately 150 h in-situ, over 11 days and 4 nights, performing observations and interviews with users. This was complemented by interviews with two staff with oversight and management responsibility related to the device. We identified 19 issues with the design and use of this device. These issues were grouped into 7 themes which can help guide the situated study of medical devices: usability, knowledge gaps and mental models, workarounds, wider tasks and equipment, the patient, connection between services, and policy.     

ADSEAT – Adaptive seat to reduce neck injuries for female and male occupants

Neck injuries sustained in low severity vehicle crashes are of worldwide concern and the risk is higher for females than for males. The objective of the study was to provide guidance on how to evaluate protective performance of vehicle seat designs aiming to reduce the incidence of neck injuries for female and male occupants. The objective was achieved by reviewing injury risk, establishing anthropometric data of an average female, performing dynamic volunteer tests comprising females and males, and developing a finite element model, EvaRID, of an average female. With respect to injury criteria, it was concluded based on the tests that using NIC (with a lower threshold value) and Nkm (with reduced intercept values) for females would be a suitable starting point. Virtual impact simulations with seats showed that differences were found in the response of the BioRID II and EvaRID models, for certain seats.     

Subjective and behavioral presence measurement and interactivity in the collaborative augmented reality game TimeWarp

Presence is usually assessed via a variety of subjective and objective measures. However, constraints often result in subjective measurements using questionnaires as a key method of data collection. In this paper we present a study of 44 participants of a collaborative augmented reality game known as TimeWarp which used both subjective and objective behavioral measures. Behavior as coded from video recordings of one scene of the game and self-reports about feelings of presence were compared. Our findings indicate that pointing behavior and verbal responses to the virtual content are correlated negatively to sense of presence. We further investigated the influence of subjectively perceived interactivity on perceived presence. We found that the interaction possibilities perceived by the participants predicted their experience of social presence with the virtual characters in the game. Furthermore, playing together with another person did not result in decreased social presence of the virtual characters. Implications for presence research are discussed.     

State equation of mineral sands

The pressure-volume analogy between compressible fluids and macroscopic sand bodies (Ivsic et al. in Phys A, 277:47–61, 2000) is further extended using quantitative determination of corresponding empirical constants based on adapted van der Waals state equation. The isothermal constants obtained by interpretation of triaxial sand tests at so called “critical state of sand” are clearly related to the universal ideal gas properties and molar properties of mineral sands. The corresponding constants for sand and gases or other volatile liquids have the same order of magnitude. The apparent bulk repulsion/attraction effects in sand bodies are also discussed.