108 research outputs found

    SARS‑CoV‑2 entry into and evolution within a skilled nursing facility

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    SARS-CoV-2 belongs to the family Coronaviridae which includes multiple human pathogens that have an outsized impact on aging populations. As a novel human pathogen, SARS-CoV-2 is undergoing continuous adaptation to this new host species and there is evidence of this throughout the scientific and public literature. However, most investigations of SARS-CoV-2 evolution have focused on largescale collections of data across diverse populations and/or living environments. Here we investigate SARS-CoV-2 evolution in epidemiologically linked individuals within a single outbreak at a skilled nursing facility beginning with initial introduction of the pathogen. The data demonstrate that SARSCoV- 2 was introduced to the facility multiple times without establishing an interfacility transmission chain, followed by a single introduction that infected many individuals within a week. This largescale introduction by a single genotype then persisted in the facility. SARS-CoV-2 sequences were investigated at both the consensus and intra-host variation levels. Understanding the variability in SARS-CoV-2 during transmission chains will assist in understanding the spread of this disease and can ultimately inform best practices for mitigation strategies

    Herausforderung Climate Engineering – Bewertung neuer Optionen für den Klimaschutz

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    [Einleitung] Der Begriff Climate Engineering (CE) fasst verschiedene Technologien zusammen, mit denen bewusst in das Klimasystem der Erde eingegriffen wird, um den anthropogenen Klimawandel zu begrenzen. Dabei lassen sich die CE-Technologien von den herkömmlichen Vermeidungs- und Anpassungsmaßnahmen durch die Tatsache abgrenzen, dass sie ansetzen, nachdem Treibhausgase in die Atmosphäre emittiert wurden, aber bevor es zu einer Anpassung an die Auswirkungen des Klimawandels kommt (Keith 2000). Sie können danach in zwei Gruppen eingeteilt werden, je nachdem ob sie eingesetzt werden, um die atmosphärische Treibhausgaskonzentration zu senken - und damit die Ursache des Klimawandels zurückzuführen - oder ob sie eingesetzt werden, um in die Strahlungsbilanz der Erde einzugreifen und damit die Symptome des Klimawandels abzumildern. Die Technologien der ersten Gruppe werden als Carbon Dioxid Removal (CDR)-Technologien und jene der anderen als Radiation Management (RM)-Technologien bezeichnet. Dabei ist Radiation Management der weitere Begriff, da sowohl Technologien zur direkten Beeinflussung der kurzwelligen (SRM) als auch der langwelligen (TRM) Strahlung beinhaltet sind. Entsprechend könnten Technologien zur ursächlichen Rückführung des Klimawandels eigentlich auch als Concentration Management bezeichnet werden, da theoretisch die atmosphärische Konzentration verschiedener Treibhausgase manipuliert werden könnte (Rickels et al. 2011: 41). Da aber derzeit nur die Konzentration von Kohlendioxid (CO2) beeinflusst wird, wird in der vorliegenden Studie der engere Begriff CDR verwendet. [...

    Improvement of late gadolinium enhancement image quality using a deep learning–based reconstruction algorithm and its influence on myocardial scar quantification

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    Objectives: The aim of this study was to assess the effect of a deep learning (DL)–based reconstruction algorithm on late gadolinium enhancement (LGE) image quality and to evaluate its influence on scar quantification. Methods: Sixty patients (46 ± 17 years, 50% male) with suspected or known cardiomyopathy underwent CMR. Short-axis LGE images were reconstructed using the conventional reconstruction and a DL network (DLRecon) with tunable noise reduction (NR) levels from 0 to 100%. Image quality of standard LGE images and DLRecon images with 75% NR was scored using a 5-point scale (poor to excellent). In 30 patients with LGE, scar size was quantified using thresholding techniques with different standard deviations (SD) above remote myocardium, and using full width at half maximum (FWHM) technique in images with varying NR levels. Results: DLRecon images were of higher quality than standard LGE images (subjective quality score 3.3 ± 0.5 vs. 3.6 ± 0.7, p < 0.001). Scar size increased with increasing NR levels using the SD methods. With 100% NR level, scar size increased 36%, 87%, and 138% using 2SD, 4SD, and 6SD quantification method, respectively, compared to standard LGE images (all p values < 0.001). However, with the FWHM method, no differences in scar size were found (p = 0.06). Conclusions: LGE image quality improved significantly using a DL-based reconstruction algorithm. However, this algorithm has an important impact on scar quantification depending on which quantification technique is used. The FWHM method is preferred because of its independency of NR. Clinicians should be aware of this impact on scar quantification, as DL-based reconstruction algorithms are being used. Key Points: • The image quality based on (subjective) visual assessment and image sharpness of late gadolinium enhancement images improved significantly using a deep learning–based reconstruction algorithm that aims to reconstruct high signal-to-noise images using a denoising technique. • Special care should be taken when scar size is quantified using thresholding techniques with different standard deviations above remote myocardium because of the large impact of these advanced image enhancement algorithms. • The full width at half maximum method is recommended to quantify scar size when deep learning algorithms based on noise reduction are used, as this method is the least sensitive to the level of noise and showed the best agreement with visual late gadolinium enhancement assessment

    Epigenetic Silencing of the Circadian Clock Gene CRY1 is Associated with an Indolent Clinical Course in Chronic Lymphocytic Leukemia

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    Disruption of circadian rhythm is believed to play a critical role in cancer development. Cryptochrome 1 (CRY1) is a core component of the mammalian circadian clock and we have previously shown its deregulated expression in a subgroup of patients with chronic lymphocytic leukemia (CLL). Using real-time RT-PCR in a cohort of 76 CLL patients and 35 normal blood donors we now demonstrate that differential CRY1 mRNA expression in high-risk (HR) CD38+/immunoglobulin variable heavy chain gene (IgVH) unmutated patients as compared to low-risk (LR) CD38−/IgVH mutated patients can be attributed to down-modulation of CRY1 in LR CLL cases. Analysis of the DNA methylation profile of the CRY1 promoter in a subgroup of 57 patients revealed that CRY1 expression in LR CLL cells is silenced by aberrant promoter CpG island hypermethylation. The methylation pattern of the CRY1 promoter proved to have high prognostic impact in CLL where aberrant promoter methylation predicted a favourable outcome. CRY1 mRNA transcript levels did not change over time in the majority of patients where sequential samples were available for analysis. We also compared the CRY1 expression in CLL with other lymphoid malignancies and observed epigenetic silencing of CRY1 in a patient with B cell acute lymphoblastic leukemia (B-ALL)

    A complex secretory program orchestrated by the inflammasome controls paracrine senescence

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    Oncogene-induced senescence (OIS) is crucial for tumour suppression. Senescent cells implement a complex pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence, activates immune surveillance and paradoxically also has pro-tumorigenic properties. Here, we present evidence that the SASP can also induce paracrine senescence in normal cells both in culture and in human and mouse models of OIS in vivo. Coupling quantitative proteomics with small-molecule screens, we identified multiple SASP components mediating paracrine senescence, including TGF-β family ligands, VEGF, CCL2 and CCL20. Amongst them, TGF-β ligands play a major role by regulating p15INK4b and p21CIP1. Expression of the SASP is controlled by inflammasome-mediated IL-1 signalling. The inflammasome and IL-1 signalling are activated in senescent cells and IL-1α expression can reproduce SASP activation, resulting in senescence. Our results demonstrate that the SASP can cause paracrine senescence and impact on tumour suppression and senescence in vivo

    Interne Unternehmenskommunikation in Theorie und Praxis. Psychologische, kommunikationswissenschaftliche und kulturvergleichende Studien

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    Niederländisch/Flämisch

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