scatterplot3d - An R Package for Visualizing Multivariate Data

Scatterplot3d is an R package for the visualization of multivariate data in a three dimensional space. R is a "language for data analysis and graphics". In this paper we discuss the features of the package. It is designed by exclusively making use of already existing functions of R and its graphics system and thus shows the extensibility of the R graphics system. Additionally some examples on generated and real world data are provided.

Nested Archimedean Copulas Meet R: The nacopula Package

The package nacopula provides procedures for constructing nested Archimedean copulas in any dimensions and with any kind of nesting structure, generating vectors of random variates from the constructed objects, computing function values and probabilities of falling into hypercubes, as well as evaluation of characteristics such as Kendall's tau and the tail-dependence coefficients. As by-products, algorithms for various distributions, including exponentially tilted stable and Sibuya distributions, are implemented. Detailed examples are given.

Insulin secretion profiles are modified by overexpression of glutamate dehydrogenase in pancreatic islets

Aims/hypothesis: Glutamate dehydrogenase (GDH) is a mitochondrial enzyme playing a key role in the control of insulin secretion. However, it is not known whether GDH expression levels in beta cells are rate-limiting for the secretory response to glucose. GDH also controls glutamine and glutamate oxidative metabolism, which is only weak in islets if GDH is not allosterically activated by L-leucine or (+/−)-2-aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH). Methods: We constructed an adenovirus encoding for GDH to overexpress the enzyme in the beta-cell line INS-1E, as well as in isolated rat and mouse pancreatic islets. The secretory responses to glucose and glutamine were studied in static and perifusion experiments. Amino acid concentrations and metabolic parameters were measured in parallel. Results: GDH overexpression in rat islets did not change insulin release at basal or intermediate glucose (2.8 and 8.3mmol/l respectively), but potentiated the secretory response at high glucose concentrations (16.7mmol/l) compared to controls (+35%). Control islets exposed to 5mmol/l glutamine at basal glucose did not increase insulin release, unless BCH was added with a resulting 2.5-fold response. In islets overexpressing GDH glutamine alone stimulated insulin secretion (2.7-fold), which was potentiated 2.2-fold by adding BCH. The secretory responses evoked by glutamine under these conditions correlated with enhanced cellular metabolism. Conclusions/interpretation: GDH could be rate-limiting in glucose-induced insulin secretion, as GDH overexpression enhanced secretory responses. Moreover, GDH overexpression made islets responsive to glutamine, indicating that under physiological conditions this enzyme acts as a gatekeeper to prevent amino acids from being inappropriate efficient secretagogue

Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

Aims/hypothesis: The expression of several neuronal genes in pancreatic beta cells is due to the absence of the transcription factor repressor element 1 (RE-1) silencing transcription factor (REST). The identification of these traits and their functional significance in beta cells has only been partly elucidated. Herein, we investigated the biological consequences of a repression of REST target genes by expressing REST in beta cells. Methods: The effect of REST expression on glucose homeostasis, insulin content and release, and beta cell mass was analysed in transgenic mice selectively expressing REST in beta cells. Relevant target genes were identified in INS-1E and primary beta cells expressing REST. Results: Transgenic mice featuring a beta cell-targeted expression of REST exhibited glucose intolerance and reduced beta cell mass. In primary beta cells, REST repressed several proteins of the exocytotic machinery, including synaptosomal-associated protein (SNAP) 25, synaptotagmin (SYT) IV, SYT VII, SYT IX and complexin II; it impaired first and second phases of insulin secretion. Using RNA interference in INS-1E cells, we showed that SYT IV and SYT VII were implicated in the control of insulin release. Conclusions/interpretation: The data document the critical role of REST target genes in pancreatic beta cells. Specifically, we provide evidence that the downregulation of these genes is detrimental for the exocytosis of large dense core vesicles, thus contributing to beta cell dysfunction and impaired glucose homeostasi

Cardiac power output accurately reflects external cardiac work over a wide range of inotropic states in pigs

BACKGROUND: Cardiac power output (CPO), derived from the product of cardiac output and mean aortic pressure, is an important yet underexploited parameter for hemodynamic monitoring of critically ill patients in the intensive-care unit (ICU). The conductance catheter-derived pressure-volume loop area reflects left ventricular stroke work (LV SW). Dividing LV SW by time, a measure of LV SW min- 1 is obtained sharing the same unit as CPO (W). We aimed to validate CPO as a marker of LV SW min- 1 under various inotropic states. METHODS: We retrospectively analysed data obtained from experimental studies of the hemodynamic impact of mild hypothermia and hyperthermia on acute heart failure. Fifty-nine anaesthetized and mechanically ventilated closed-chest Landrace pigs (68 ± 1 kg) were instrumented with Swan-Ganz and LV pressure-volume catheters. Data were obtained at body temperatures of 33.0 °C, 38.0 °C and 40.5 °C; before and after: resuscitation, myocardial infarction, endotoxemia, sevoflurane-induced myocardial depression and beta-adrenergic stimulation. We plotted LVSW min- 1 against CPO by linear regression analysis, as well as against the following classical indices of LV function and work: LV ejection fraction (LV EF), rate-pressure product (RPP), triple product (TP), LV maximum pressure (LVPmax) and maximal rate of rise of LVP (LV dP/dtmax). RESULTS: CPO showed the best correlation with LV SW min- 1 (r2 = 0.89; p < 0.05) while LV EF did not correlate at all (r2 = 0.01; p = 0.259). Further parameters correlated moderately with LV SW min- 1 (LVPmax r2 = 0.47, RPP r2 = 0.67; and TP r2 = 0.54). LV dP/dtmax correlated worst with LV SW min- 1 (r2 = 0.28). CONCLUSION: CPO reflects external cardiac work over a wide range of inotropic states. These data further support the use of CPO to monitor inotropic interventions in the ICU

Bioconductor: open software development for computational biology and bioinformatics.

The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples

Eigenschaften, Häufigkeit und Verbreitung von Vancomycin-resistenten Enterokokken in Deutschland – Update

Vancomycin-resistente Enterokokken (VRE) gehören zu den in Deutschland gemäß § 23 Abs. 4 IfSG zu erfassenden Erregern und werden in vielen deutschen Kliniken häufig beobachtet. Der Nachweis von VRE ist in den zurückliegenden Jahren auf einem stabil hohen Niveau in Deutschland und bewegt sich leicht oberhalb des EU-Durchschnitts. Die Krankheitslast durch invasive VRE-Infektionen ist hingegen nachweislich ansteigend. Das Nationale Referenzzentrum für Staphylokokken und Enterokokken beobachtet diese Entwicklungen und berichtet über die Situation von VRE und Enterokokken mit besonderen Antibiotikaresistenzen im Zeitraum 2021/2022. Darüber hinaus wird auf allgemeine VRE-Resistenzsta¬tistiken nationaler Erhebungssysteme und -studien hingewiesen.Peer Reviewe

Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

AIMS/HYPOTHESIS: The expression of several neuronal genes in pancreatic beta cells is due to the absence of the transcription factor repressor element 1 (RE-1) silencing transcription factor (REST). The identification of these traits and their functional significance in beta cells has only been partly elucidated. Herein, we investigated the biological consequences of a repression of REST target genes by expressing REST in beta cells. METHODS: The effect of REST expression on glucose homeostasis, insulin content and release, and beta cell mass was analysed in transgenic mice selectively expressing REST in beta cells. Relevant target genes were identified in INS-1E and primary beta cells expressing REST. RESULTS: Transgenic mice featuring a beta cell-targeted expression of REST exhibited glucose intolerance and reduced beta cell mass. In primary beta cells, REST repressed several proteins of the exocytotic machinery, including synaptosomal-associated protein (SNAP) 25, synaptotagmin (SYT) IV, SYT VII, SYT IX and complexin II; it impaired first and second phases of insulin secretion. Using RNA interference in INS-1E cells, we showed that SYT IV and SYT VII were implicated in the control of insulin release. CONCLUSIONS/INTERPRETATION: The data document the critical role of REST target genes in pancreatic beta cells. Specifically, we provide evidence that the downregulation of these genes is detrimental for the exocytosis of large dense core vesicles, thus contributing to beta cell dysfunction and impaired glucose homeostasis

Therapierelevante Antibiotikaresistenzen im One-Health-Kontext

„One Health“ bezeichnet ein Konzept, das die Gesundheit von Menschen, Tieren und der Umwelt miteinander verbindet. In Deutschland gibt es umfangreiche Daten zur Antibiotikaresistenz (AMR) und multiresistenten Erregern (MRE) in der Human- und Veterinärmedizin sowie aus Untersuchungen in verschiedenen Umweltkompartimenten (Boden, Wasser, Abwasser). Die Erhebung erfolgt nach unterschiedlichen Vorgaben und Standards, was den Vergleich von Daten erschwert. Ein Fokus auf humantherapeutisch wichtige AMR und MRE ist hilfreich, um eine gewisse Orientierung vorzugeben. Die meisten Daten liegen sektorübergreifend zu Methicillin-resistenten Staphylococcus aureus und multiresistenten Enterobacterales wie Escherichia coli und Klebsiella pneumoniae vor. Hier sind die Trends der Resistenzen heterogen. Der Einsatz von Antibiotika führt zur Selektion von MRE, was gut dokumentiert ist. Erfolge bei der Minimierung des Antibiotikaeinsatzes konnten in zurückliegenden Jahren für einzelne Sektoren dargestellt und z. T. mit Erfolgen in der Eindämmung von AMR und MRE korreliert werden (Rückgang MRSA in der Humanmedizin). Auch sektorspezifische Maßnahmen zur Senkung der Last durch MRE und AMR sind notwendig, da Resistenzprobleme nicht generell eine Verknüpfung mit anderen Sektoren aufweisen. Carbapenemresistenzen sind vor allem bei pathogenen Erregern vom Menschen nachweisbar. Colistinresistenzen kommen in verschiedenen Sektoren vor, zeigen aber dort jeweils verschiedene Mechanismen. Resistenzen gegen Reservesubstanzen wie Linezolid sind in Deutschland selten, sie zeigen aber einen konkreten One-Health-Bezug. Bestrebungen zur Harmonisierung von Methoden, z. B. im Bereich der antimikrobiellen Empfindlichkeitstestung und genombasierten Erreger- und AMR-Surveillance, sind ein wichtiger erster Schritt zu einer Vergleichbarkeit der verschiedenen Datenerhebungen.One Health refers to a concept that links human, animal, and environmental health. In Germany, there is extensive data on antibiotic resistance (AMR) and multidrug-resistant (micro)organisms (MDRO) in human and veterinary medicine, as well as from studies in various environmental compartments (soil, water, wastewater). All these activities are conducted according to different specifications and standards, which makes it difficult to compare data. A focus on AMR and MDRO of human therapeutic importance is helpful to provide some guidance. Most data are available across sectors on methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Enterobacterales such as Escherichia coli and Klebsiella pneumoniae. Here, the trends of resistance are heterogeneous. Antibiotic use leads to MRE selection, which is well documented. Success in minimizing antibiotic use has also been demonstrated in recent years in several sectors and could be correlated with success in containing AMR and MDRO (e.g., decrease in MRSA in human medicine). Sector-specific measures to reduce the burden of MDRO and AMR are also necessary, as not all resistance problems are linked to other sectors. Carbapenem resistance is still rare, but most apparent in human pathogens. Colistin resistance occurs in different sectors but shows different mechanisms in each. Resistance to antibiotics of last resort such as linezolid is rare in Germany, but shows a specific One Health correlation. Efforts to harmonize methods, for example in the field of antimicrobial susceptibility testing and genome-based pathogen and AMR surveillance, are an important first step towards a better comparability of the different data collections.Peer Reviewe