Late to post-Variscan basement segmentation and differential exhumation along the SW Bohemian Massif, central Europe

The exposed Variscan basement in central Europe is well-known for its complex structural and lithological architecture resulting from multiple deformation phases. We studied the southwestern margin of the Bohemian Massif, which is characterized by major and long-lived shear zones, such as the Pfahl and Danube shear zones, extending over > 100 km and initiated during Variscan tectonics. We integrated Bouguer gravity anomaly and lidar topographic data analyses and combined our results with available data and observations from low-temperature thermochronology, metamorphic grades, and the exposed granite inventory to detect patterns of basement block segmentation and differential exhumation. Three NW–SE-striking basement blocks are bordered by the Runding, Pfahl, and Danube shear zones from the northeast to the southwest. Basement block boundaries are indicated by abrupt changes in measured gravity patterns and metamorphic grades. By applying high-pass filters to gravity data in combination with lineament analysis, we identified a new NNW–SSE-striking tectonic structure (Cham Fault), which further segments known basement blocks. Basement blocks that are segmented by the Cham Fault differ in the abundance and spatial distribution of exposed late Variscan granites and are further characterized by variations in apparent thermochronological age data. Based on our observations and analyses, a differential exhumation and tectonic tilt model is proposed to explain the juxtaposition of different crustal levels. Block segmentation along the NW–SE-striking Pfahl and Runding shear zones most likely occurred prior, during, and after late orogenic granite emplacement at ca. 320 ± 10 Ma, as some of the granites are cross-cut by the shear zones, while others utilized these structures during magma ascent and emplacement. In contrast, activity and block segmentation along the Cham Fault occurred after granite emplacement as the fault sharply truncates the granite inventory. Our study provides evidence of intense and continuous fault activities during late and post-orogenic times and highlights the importance of tectonic structures in the exhumation and juxtaposition of different crustal levels and the creation of complex lithological patterns in orogenic terrains

BMSC–HNC Interaction: Exploring Effects on Bone Integrity and Head and Neck Cancer Progression

In recent research, the tumor microenvironment has been shown to attract mesenchymal stromal cells (MSCs), which is of particular interest due to its implications for cancer progression. The study focused on understanding the interaction between bone marrow-derived MSCs (BMSCs) and head and neck cancer (HNC) cells. This interaction was found to activate specific markers, notably the osteogenic marker alkaline phosphatase and the oncogene Runx2. These activations corresponded with the release of collagenase enzymes, MMP9 and MMP2. To gain insights into bone resorption related to this interaction, bovine bone slices were used, supporting the growth of “heterogeneous spheroids” that contained both BMSCs and HNC cells. Through scanning electron microscopy and energy-dispersive X-ray (EDX) analysis, it was observed that these mixed spheroids were linked to a notable increase in bone degradation and collagen fiber exposure, more so than spheroids of just BMSCs or HNC cells. Furthermore, the EDX results highlighted increased nitrogen content on bone surfaces with these mixed clusters. Overall, the findings underscore the significant role of BMSCs in tumor growth, emphasizing the need for further exploration in potential cancer treatment strategies

Scandinavian Higher Education Governance – Pursuing Similar Goals through Different Organizational Arrangements

Under embargo until: 2022-02-03The differences and similarities among the three Scandinavian countries, Denmark, Norway, and Sweden have been discussed by social scientists on several occasions. Focusing on higher education (HE) governance systems, this paper raises three questions. (1) What are the differences and similarities among the three countries? (2) How can the similarities and differences be explained? (3) Are the similarities strong enough to justify the common label of a Scandinavian model of HE governance? The three HE governance systems are briefly described and compared. They are then analyzed as, respectively, outcomes of partisan politics or politico-administrative regimes. The paper argues that similarities such as publicness, massive investments, and emphasis on access are best explained in terms of partisan politics, while the variation in governance arrangements can best be explained by path dependencies following choices made at critical junctures within similar politicoadministrative regimes.acceptedVersio

CTLA-4 Activation of Phosphatidylinositol 3-Kinase (PI 3-K) and Protein Kinase B (PKB/AKT) Sustains T-Cell Anergy without Cell Death

The balance of T-cell proliferation, anergy and apoptosis is central to immune function. In this regard, co-receptor CTLA-4 is needed for the induction of anergy and tolerance. One central question concerns the mechanism by which CTLA-4 can induce T-cell non-responsiveness without a concurrent induction of antigen induced cell death (AICD). In this study, we show that CTLA-4 activation of the phosphatidylinositol 3-kinase (PI 3-K) and protein kinase B (PKB/AKT) sustains T-cell anergy without cell death. CTLA-4 ligation induced PI 3K activation as evidenced by the phosphorylation of PKB/AKT that in turn inactivated GSK-3. The level of activation was similar to that observed with CD28. CTLA-4 induced PI 3K and AKT activation also led to phosphorylation of the pro-apoptotic factor BAD as well as the up-regulation of BcL-XL. In keeping with this, CD3/CTLA-4 co-ligation prevented apoptosis under the same conditions where T-cell non-responsiveness was induced. This effect was PI 3K and PKB/AKT dependent since inhibition of these enzymes under conditions of anti-CD3/CTLA-4 co-ligation resulted in cell death. Our findings therefore define a mechanism by which CTLA-4 can induce anergy (and possibly peripheral tolerance) by preventing the induction of cell death

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

A multicentre randomised controlled trial evaluating lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea in older people admitted to hospital: the PLACIDE study protocol

<p>Abstract</p> <p>Background</p> <p>Antibiotic associated diarrhoea complicates 5–39% of courses of antibiotic treatment. Major risk factors are increased age and admission to hospital. Of particular importance is <it>C. difficile</it> associated diarrhoea which occurs in about 4% of antibiotic courses and may result in severe illness, death and high healthcare costs. The emergence of the more virulent 027 strain of <it>C. difficile</it> has further heightened concerns. Probiotics may prevent antibiotic associated diarrhoea by several mechanisms including colonization resistance through maintaining a healthy gut flora.</p> <p>Methods</p> <p>This study aims to test the hypothesis that administration of a probiotic comprising two strains of lactobacilli and two strains of bifidobacteria alongside antibiotic treatment prevents antibiotic associated diarrhoea. We have designed a prospective, parallel group trial where people aged 65 years or more admitted to hospital and receiving one or more antibiotics are randomly allocated to receive either one capsule of the probiotic or a matching placebo daily for 21 days. The primary outcomes are the frequency of antibiotic associated and <it>C. difficile</it> diarrhoea during 8–12 weeks follow-up. To directly inform routine clinical practice, we will recruit a sufficient number of patients to demonstrate a 50% reduction in the frequency of <it>C. difficile</it> diarrhoea with a power of 80%. To maximize the generalizability of our findings and in view of the well-established safety record of probiotics, we will recruit a broad range of medical and surgical in-patients from two different health regions within the UK.</p> <p>Discussion</p> <p>Antibiotic associated diarrhoea constitutes a significant health burden. In particular, current measures to prevent and control <it>C. difficile</it> diarrhoea are expensive and disrupt clinical care. This trial may have considerable significance for the prevention of antibiotic associated diarrhoea in hospitals.</p> <p>Trial registration</p> <p>International Standard Randomised Controlled Trial Number Register ISRCTN70017204.</p

The Nachtlichter app: a citizen science tool for documenting outdoor light sources in public space

The relationship between satellite based measurements of city radiance at night and the numbers and types of physical lights installed on the ground is not well understood. Here we present the "Nachtlichter app", which was developed to enable citizen scientists to classify and count light sources along street segments over large spatial scales. The project and app were co-designed: citizen scientists played key roles in the app development, testing, and recruitment, as well as in analysis of the data. In addition to describing the app itself and the data format, we provide a general overview of the project, including training materials, data cleaning, and the result of some basic data consistency checks