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BACKGROUND: Inflammation plays a pivotal role in coronary artery disease (CAD). The anti- inflammatory drug colchicine seems to reduce ischemic events in patients with CAD. So far there is equipoise about its safety and impact on mortality METHODS AND RESULTS: To evaluate the utility of colchicine in patients with acute and chronic CAD, we performed a systematic review and meta- analysis. MEDLINE, EMBASE, Cochrane CENTRAL and conference abstracts were searched from January 1975 to October 2020. Randomized trials assessing colchicine compared with placebo/standard therapy in patients with CAD were included. Data were combined using random- effects models. The reliability of the available data was tested using trial sequential analyses. Of 3108 citations, 13 randomized trials (n=13 125) were included. Colchicine versus placebo/standard therapy in patients withCAD reduced risk of myocardial infarction (odds ratio [OR] 0.64; 95% CI, 0.46 ��� 0.90; P= 0.01; I 41%) and stroke/transient ischemic attack (OR 0.50; 95% CI, 0.31��� 0.81; P=0.005; I 0%). But treatment with colchicine compared with placebo/standard therapy had no influence on all- cause and cardiovascular mortality (OR 0.96; 95% CI, 0.65��� 1.41; P=0.83; I 24%; and OR 0.82; 95% CI, 0.55��� 1.22; P=0.45; I 0%, respectively). Colchicine increased the risk for gastrointestinal side effects (P, + ID der Publikation: unilu_54969 + Sprache: Englisch + Letzte Aktualisierung: 2021-10-27 16:06:46

A 25 year old woman was referred to our center for further evaluation of an exercise-induced dyspnea. Moreover, the patient suffered from hoarseness and recurrent sinusitis and otitis.After initially finding nothing suspicious, a spiro-ergometry was performed. Interestingly, we saw a relevant limitation of the inspiratory flow-volume curve under maximal exercise load. Further evaluation (in particular the bronchoscopy and the resulting biopsies) led us to the final diagnosis of a granulomatosis with polyangiitis.After 4 weeks of an established therapy regime with prednisone and rituximab the prior detected subglottic stenosis and the inspiratory flow-volume curve limitation could no longer detected.We describe a rare differential diagnosis of an exercise-induced asthma and we underline the importance of a multimodal therapy concept. We highlight the critical nature of the flow-volume curve in spiro-ergometry under maximal exercise load. We recommend frequent follow-up control visits to monitor the subglottic stenosis. Keywords: Asthma, Exercise induced, GPA

A 55-year-old male patient under permanent testosterone therapy for hypogonadism presented with abdominal pain and increased blood pressure values. In the physical examination a plethora was noted and laboratory examinations revealed polyglobulia. In the subsequent diagnostic process polycythemia vera and cancer could be excluded as the cause. A secondary polyglobulia due to testosterone substitution was diagnosed. Unphysiologically high testosterone levels represent a rare cause of secondary polyglobulia and with an appropriate medical history should be taken into account at an early stage.

The relevance of the soil moisture content (SMC) for runoff processes and thus for flood prediction is rather undisputed; however, there are still gaps in our knowledge of the precipitation – soil moisture reaction pattern. A new event-based approach, using statistical methods to analyse monitoring data, is presented and applied for soil moisture data of three test sites, situated in different parts of the Tyrolean Alps (Austria). The analyses revealed a significant influence of the initial soil moisture on the remaining soil storage capacity. A comparison of the value pairs initial soil moisture and soil moisture difference (SMCmax caused by rain events minus initial SMC) resulted in funnel-shaped distributions, whereby the upper boundary of the data should roughly match the field capacity of the soils. For purposes of flood prediction, precipitation sums and initial conditions are the relevant variables, while precipitation duration, intensities, and antecedent precipitation have significantly less influence on SMC. However, the functions describing the relationship between precipitation and SMC showed poor model fits despite their significance. The linkage of soil moisture content between different depths, which, inter alia, are important when using remote sensing data for spatial SMC estimations, showed that the soil moisture conditions in the upper layer do not necessarily represent the water storage state of the deeper layers. The relation strongly depends on the kind of transition between the horizons, underlining the great importance of proper spatial information on soil characteristics. Approaches to estimate the initial SMC at the beginning of heavy rainfall events on the basis of antecedent precipitation sums are not very promising due to the weak relationships between these parameters.

BACKGROUND Patients with atrial fibrillation (AF) have an increased risk of cognitive decline, potentially resulting from clinically unrecognized vascular brain lesions. OBJECTIVES This study sought to assess the relationships between cognitive function and vascular brain lesions in patients with AF. METHODS Patients with known AF were enrolled in a multicenter study in Switzerland. Brain magnetic resonance imaging (MRI) and cognitive testing using the Montreal Cognitive Assessment (MoCA) were performed in all participants. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions were quantified by a central core laboratory. Clinically silent infarcts were defined as infarcts on brain MRI in patients without a clinical history of stroke or transient ischemic attack. RESULTS The study included 1,737 patients with a mean age of 73 ± 8 years (28% women, 90% taking oral anticoagulant agents). On MRI, LNCCIs were found in 387 patients (22%), SNCIs in 368 (21%), microbleeds in 372 (22%), and white matter lesions in 1715 (99%). Clinically silent infarcts among the 1,390 patients without a history of stroke or transient ischemic attack were found in 201 patients with LNCCIs (15%) and 245 patients with SNCIs (18%). The MoCA score was 24.7 ± 3.3 in patients with and 25.8 ± 2.9 in those without LNCCIs on brain MRI (p < 0.001). The difference in MoCA score remained similar when only clinically silent LNCCIs were considered (24.9 ± 3.1 vs. 25.8 ± 2.9; p < 0.001). In a multivariable regression model including all vascular brain lesion parameters, LNCCI volume was the strongest predictor of a reduced MoCA (β = -0.26; 95% confidence interval: -0.40 to -0.13; p < 0.001). CONCLUSIONS Patients with AF have a high burden of LNCCIs and other brain lesions on systematic brain MRI screening, and most of these lesions are clinically silent. LNCCIs were associated with worse cognitive function, even among patients with clinically silent infarcts. Our findings raise the question of MRI screening in patients with AF.

Plasma levels of natriuretic peptides (NP) have been inversely related to hemoglobin (Hb) concentration in prior studies. However, the mechanism underlying this association remains unclear. We aimed to obtain further insights into potential mechanisms for this correlation in a cohort of healthy adults.A population-based study was performed among 2113 healthy adults aged 25-41years. Relationships of N-Terminal fragment of Pro-B-Type Natriuretic Peptide (NT-proBNP) or copeptin with volume-dependent (Hb, hematocrit (Hct), erythrocyte count (EC), mean corpuscular Hb concentration (MCHC)) and volume-independent (mean corpuscular volume (MCV), mean corpuscular Hb (MCH)) erythrocyte-related parameters were assessed using sex-specific multivariable linear regression analyses.The median age was 36.7years. Median NT-proBNP (ng/L) levels were 49.5 and 20 among women and men, respectively (p0.0001). Mean (standard deviation) Hb (g/L) levels were 130.1(9.1) and 149.7(8.6) among women and men, respectively (p0.0001). Among men, multivariable adjusted β-coefficients (95% confidence interval) for NT-proBNP were -1.68 (-2.36; -1.01), p0.0001 for Hb; -0.38 (-0.57; -0.20), p0.0001 for Hct; -0.06 (-0.09; -0.04), p0.0001 for EC; -0.78 (-1.50; -0.07), p=0.03 for MCHC; 0.26 (-0.04; 0.56), p=0.09 for MCV; and 0.03 (-0.08; 0.14), p=0.61 for MCH. For copeptin, these relationships were 1.36 (0.39; 2.32), p=0.006; 0.41 (0.15; 0.68), p=0.002; 0.06 (0.02; 0.09), p=0.002; -0.17 (-1.19; 0.86), p=0.75; -0.12 (-0.55; 0.31), p=0.58 and -0.05 (-0.21; 0.10), p=0.52. Similar results were observed among women.We found significant relationships of NT-proBNP and copeptin with volume-dependent but not volume-independent erythrocyte-related parameters, suggesting that hemodilution may at least in part explain these associations.

Durch die Vielzahl von Themengebieten, die unmittelbar mit der Digitalisierung zusammenhangen, ist es fur Unternehmen haufig schwer, die ersten Schritte zu gehen. In diesem Kapitel widmen wir uns der Entwicklung einer Digitalstrategie durch eine Vielzahl von Kompetenzfragen in unterschiedlichen Kategorien. Die Antworten auf diese Kompetenzfragen sollen die Grundlage fur eine Digitalstrategie bilden und geben fur das Unternehmen eine erste grobe Richtung vor, die in der Erarbeitung von Digitalisierungsvorhaben hilft, auf die wesentlichen Herausforderungen zu fokussieren.

Die digitale Transformation in Unternehmen erfordert Kompetenzen in unterschiedlichen Fachgebieten. Dieses Kapitel behandelt die notwendigen Kompetenzen in Abhangigkeit der Betrachtungsdimensionen und schlagt mogliche Teamkonstellationen vor. Daruber hinaus wird argumentiert, welche Rollen beratend und mitwirkend Beteiligte haben sollen und welche methodischen Kompetenzen, uber die fachlichen hinaus, erforderlich sind, um ein Digitalisierungsvorhaben erfolgreich durchfuhren zu konnen.

In der Analyse- und Innovationsdimension wird initial eine Umwelt- und Unternehmensanalyse durchgefuhrt. Fur die Analyse stellt das Buch mehrere Ansatze vor, die sich hierfur eignen. Im Bereich der Innovation widmet sich das Kapitel einer durchgehenden Methode fur die Entwicklung von Ideen und darauf basierenden Innovationen. Die Ergebnisse der Analyse und der Innovation sind Inhalte fur die Digitalisierungsaspekte im Bereich „einwirkende Einflusse“ und „ausgehende Interaktionen“. Ein Digitalisierungsvorhaben hat immer das Ziel, die ausgehenden Interaktionen zu realisieren.

Viele der Veranderungen der Digitalisierung haben unmittelbaren Einfluss auf Unternehmen. Initial stellen wir in diesem Kapitel die einfachen Grunde und Zusammenhange von Veranderungen vor, die auf Unternehmen durch die Digitalisierung zukommen. Eine wichtige Facette der Digitalisierung ist eine veranderte Kultur in Unternehmen, die sich z.B. in einer veranderten Fuhrungskultur zeigt. Aber auch die Art der Projektdurchfuhrung verandert sich durch volatilere Anforderungen und Technologieentwicklungen. Das Kapitel schliest mit den Auswirkungen auf Ablaufe innerhalb von Unternehmen ab.

Die Vorgehensweise, die mit dem Digital-Base-Modell eingefuhrt wird, sieht den Durchlauf von drei Betrachtungsdimensionen vor. In diesen Betrachtungsdimensionen werden Teilaktivitaten durchgefuhrt, die in diesem Kapitel vorgestellt werden. Teilaktivitaten liefern Ergebnisse, die, abhangig von der Priorisierung von Zielen, unterschiedlich ausgewahlt werden konnen. Dieses Kapitel behandelt weiter, wie lange die Durchfuhrung eines Digitalisierungsvorhabens typischerweise dauert und welche finanziellen Kosten mit der Durchfuhrung verbunden sind.

In der Definitions- und Integrationsdimension wird das eigentliche Digitalisierungsszenario erstellt. Die Ergebnisse aus der Analyse und der Innovationsentwicklung werden in ein Digitalisierungsvorhaben ubernommen. Die internen Digitalisierungsaspekte eines Unternehmen werden dann in Anbetracht der zu erfullenden Ziele erfasst. Die Integration eines Digitalisierungsszenarios bezeichnet die Ubernahme der Strategie und des Geschaftsmodells eines Digitalisierungsszenarios in die Strategie und das Geschaftsmodell eines Unternehmens. Hierfur ist die Unterstutzung des Top-Managements erforderlich. Dieses Kapitel beschreibt abschliesend, wie diese Integration vollzogen werden kann.

BACKGROUND Lower birthweight is associated with an increased risk of cardiovascular diseases and diabetes. We hypothesized that inflammation and body fat may be potential mediators for these inverse relationships. MATERIALS AND METHODS Healthy adults aged 25-41 years were enrolled in a prospective population-based cohort study in the Principality of Liechtenstein. Main exclusion criteria were diabetes, overt cardiovascular disease or a body mass index > 35 kg/m(2) . Birthweight was self-reported by the study participants. White blood cell (WBC) count and high-sensitivity C-reactive protein (hs-CRP) levels were assayed from fresh blood samples. Body composition was determined by bioelectrical impedance analysis. Multivariable linear regression models were constructed to assess the relationships between birthweight, inflammation and body composition. RESULTS Our sample consisted of 1774 participants (53·4% females) with a median age of 37 years. Median birthweight was 3355 g. In multivariable models, we found an inverse relationship of birthweight with hs-CRP levels (β -0·010 (95% CI -0·02; -0·002), P = 0·01) and WBC count (β -0·002 (95% CI -0·004; -0·0002), P = 0·03). Additional adjustment for body fat mass attenuated these relationships (β -0·008 (95% CI -0·02; 0·0003), P = 0·06 for hs-CRP levels and (β -0·002 (95% CI -0·004; 0·0006), P = 0·16 for WBC count. Body fat mass itself was strongly associated with birthweight (β -0·06 (95% CI -0·10; -0·03), P < 0·0001). CONCLUSION Birthweight is inversely associated with inflammation in adulthood. This relationship may be mediated by an elevated body fat mass among individuals with lower birthweight.

Several biomarkers within the iron metabolism pathway have been related to the occurrence of diabetes mellitus, but underlying mechanisms are unknown. The aim of our study was to investigate the differential relationships of iron metabolism with a broad range of diabetes markers in young and healthy adults.2160 participants aged 25 to 41years were enrolled in a population-based study. Established cardiovascular disease, diabetes or a body mass index35kg/m(2) were exclusion criteria. Multivariable linear regression models were built to assess the associations of ferritin and transferrin saturation (TSAT) with blood levels of glucagon-like peptide-1 (GLP-1), insulin, homeostatic model assessment-insulin resistance (HOMA-IR), fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c).Median (interquartile range) age was 37 (31, 40) years. In multivariable linear regression analyses, β-coefficients (95% confidence intervals) per 1-SD increase in ferritin were 0.04 (0.02; 0.07, p=0.0008) for GLP-1, 0.06 (0.04; 0.08, p0.0001) for insulin, 0.07 (0.04; 0.09, p0.0001) for HOMA-IR, 0.004 (-0.00; 0.01, p=0.07) for FPG and -0.003 (-0.01; -0.00, p=0.07) for HbA1c. β-coefficients (95% CI) per 1-SD increase in TSAT were -0.07 (-0.09; -0.05, p0.0001) for GLP-1, -0.06 (-0.08; -0.04, p0.0001) for insulin, -0.07(-0.09; -0.05, p0.0001) for HOMA-IR, -0.01 (-0.01; -0.00, p0.0001) for FPG and -0.01 (-0.01; -0.00, p=0.0004) for HbA1c.Markers of insulin resistance are strongly related with markers of iron metabolism in healthy subjects. These relationships were inconsistent and weaker for short-term and long-term glucose levels. These results may provide insights in the relationships between iron metabolism and diabetes occurrence.

During the systems engineering process many heterogeneous artifacts which belong to different engineering disciplines and describe different views upon the product to be developed are produced. In order to integrate these artifacts, to increase the level of reuse, or to evaluate and implement changes, we need semantically rich relations between development artifacts and the parts of the product they describe. In this paper, we present our research to extend the IEEE Standard Upper Ontology with a mid-level layer which can be used as a reusable semantic basis for making the knowledge about the developed product, the development artifacts, and the relations between them explicit.

Teamwork is a prerequisite for the development of large complex software systems. In conventional software engineering coordination of teamwork is achieved by exchanging formal documents and by providing support for keeping these documents consistent even while several developers are evolving them. In order to support teamwork more effectively it is important to move the focus beyond coordination towards cooperation. The goal of the Beyond-Sniff project is to provide cooperation support in three ways. First, by providing a terminological and conceptional foundation for the field of cooperative software engineering. Second, by developing tools for computer supported cooperative software engineering. Third, by developing a platform for control and data integration, a technical prerequisite for computer supported cooperative software engineering. >