1,720,975 research outputs found

    Analysis of acute COVID-19 including chronic morbidity: protocol for the deep phenotyping National Pandemic Cohort Network in Germany (NAPKON-HAP)

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    Abstract Background The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). Methods NAPKON-HAP is a multi‐centered prospective observational study with a long‐term follow‐up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. Results Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. Conclusion NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    Wirksamkeit und Wirkmechanismus synthetischer GPI-Glykokonjugat-Impfstoffe bei zerebraler Malaria im Mausmodell

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    Background: Cerebral malaria is the most severe manifestation of Plasmodium falciparum malaria. Sensing of Plasmodium-specific pathogen-associated molecular patterns such as glycosylphosphatidylinositol (GPI) by the host pattern recognition receptors leads to the induction of pro inflammatory pathways, and has been shown to be a major contributor to cerebral malaria pathogenesis. Carbohydrate-based vaccines have widely been applied and successfully prevented disease and death in recent decades. An antitoxic GPI glycoconjugate vaccine therefore represents a promising approach to preventing cerebral malaria pathogenesis. Method: Six structurally distinct GPI glycans were synthesized and conjugated to CRM197. GPI1 and GPI2 both containing Man3-GlcN, with PEthN attached to GPI2; GPI3 and GPI4 core structures containing Man4-GlcN, with PEthN attached to GPI4; and GPI5 (Man3-GlcN) and GPI6 (Man4 GlcN) both containing PEthN and PI. Glycoconjugates were tested for immunogenicity and efficacy in C57BL/6JRj mice susceptible to experimental cerebral malaria (ECM). Mice were immunized three times intraperitoneally at 14-day intervals and were finally challenged with 1x106 erythrocytes infected with P. berghei ANKA (PbA). Serum samples were obtained before immunizations to determine anti GPI antibody level. Prior to onset of ECM (day 6 post infection), 5 mice per group were sacrificed to investigate spleen cell composition, brain T cell sequestration and vaccine specific T cell re- stimulation. The remaining 10 mice per group were used for survival studies. Results: Mice immunized with GPI2, GPI4, GPI5 and GPI6 developed significantly increased anti GPI antibodies compared to control mice. Only a slight increase was observed in mice immunized with GPI1 and GPI3. Control mice succumbed to experimental cerebral malaria in 100% of cases, whereas all GPI- CRM197-immunized mice displayed an improved survival. In particular, GPI5-vaccinated mice were significantly protected against PbA-induced encephalopathy with 40% survival. Immunological characterization of spleen cell population and serum cytokines did not reveal significant differences between GPI-CRM197-vaccinated groups. However, distinct trends were observed, with GPI5 showing decreased cellular activation and reduced levels of serum cytokines TNF-α, IFN-γ and IL-6. Conclusion: In this study, the efficacy and immunogenicity of structurally distinct GPI glycoconjugate vaccines was investigated. For the first time, the approved non-toxic mutant of diphtheria toxin CRM197 and alum were applied in this glycoconjugate formulation. A structure activity relationship of different synthetic GPIs with respect to immunogenicity by glycan array analysis was established. Further, the effectiveness of the GPI-antitoxic vaccine approach could be reproduced with a diminished pro inflammatory immune response against Plasmodium GPI, preventing disease pathology and death in some of the glycoconjugates tested. In conclusion, this study adds to current evidence that a GPI-antitoxic vaccine provides protection against Plasmodium GPI-induced ECM.Hintergrund: Die zerebrale Malaria gehört zu den schwersten Verlaufsformen der durch Plasmodium falciparum verursachten Malaria tropica. Die Erkennung von pathogen-assoziierten molekularen Mustern, wie beispielsweise parasitäres Glykosylphosphatidylinositol (GPI) durch Mustererkennungsrezeptoren, führt zur Induktion einer proinflammatorischen Reaktion des Wirtes. Dieser konnte eine entscheidende Rolle in der Pathogenese der zerebralen Malaria nachgewiesen werden. Kohlenhydrat-basierte Impfstoffe sind ein essentieller Bestandteil der aktuell zugelassenen Vakzine und spielen eine wichtige Rolle in der Prävention von Infektionskrankheiten. Ein antitoxischer GPI-Glykokonjugat-Impfstoff ist daher ein vielversprechender Ansatz zur Prävention der zerebralen Malaria. Methode: Sechs strukturell verschiedene GPI-Glykane wurden synthetisiert und an CRM197 konjugiert: GPI1 und GPI2 jeweils basierend auf Man3-GlcN, mit PEthN zusätzlich an GPI2 gebunden; GPI3 und GPI4 basierend auf Man4-GlcN, mit PEthN an GPI4 gebunden; sowie GPI5 (Man3-GlcN) und GPI6 (Man4-GlcN) jeweils mit PEthN und PI versehen. Alle Glykokonjugate wurden an für die experimentelle zerebrale Malaria (ECM) empfänglichen C57BL/6JRj Mäusen hinsichtlich Immunogenität und Wirksamkeit getestet. Die Immunisierung wurde intraperitoneal in 14-tägigen Abständen appliziert und den Versuchstieren anschließend 1x106 P. berghei ANKA (PbA) infizierte Erythrozyten injiziert. Serumproben wurden vor den Immunisierungen entnommen. 5 Mäuse wurden zur detaillierten Analyse von Milzzellpopulationen, zerebraler T Zell Sequestrierung und Impfstoff-spezifischen T-Zell Re-stimulation vor Auftreten ECM spezifischer Symptome (Tag 6 post infectionem) pro Gruppe verwendet. Mit den verbleibenden 10 Mäusen wurde die Wirksamkeit der Impfstoffe mittels Überlebensstudien durchgeführt. Ergebnisse: GPI2, GPI4, GPI5 und GPI6 immunisierte Mäuse entwickelten signifikant höhere anti GPI Antikörper im Vergleich zu Kontrolltieren. Für GPI1 und GPI3 konnte nur ein leichter Anstieg beobachtet werden. Insgesamt war die Prävalenz der ECM bei den Kontrollmäusen 100%, wohingegen alle GPI CRM197 immunisierten Mäuse eine verbesserte Überlebensrate aufwiesen. Insbesondere konnte bei GPI5 geimpften Mäusen ein signifikanter Schutz gegen PbA induzierte Enzephalopathie festgestellt werden. Die immunologische Charakterisierung von Milz Zellpopulation und Serum Zytokinen zeigte keine signifikanten Unterschiede zwischen den GPI-CRM197 geimpften Gruppen. Es konnten jedoch Tendenzen beobachtet werden, wobei GPI5 immunisierte Mäuse eine verringerte Zellaktivierung sowie ebenfalls verringerte TNF-α, IFN-γ und IL-6 Spiegel im Serum aufwiesen. Diskussion: In dieser Studie konnte die Wirksamkeit und der Wirkmechanismus eines GPI Glykokonjugat-Impfstoffes weiter untersucht werden. Zum ersten Mal wurden das zugelassene Trägerprotein CRM197 und Alum als Adjuvans verwendet. Es ließ sich eine Struktur Funktionsbeziehung verschiedener synthetischer GPI-Konstrukte in Bezug auf die Immunogenität mittels Glycan Array-Analyse herstellen. Ferner konnte die anti inflammatorische Wirksamkeit antitoxischer GPI-Impfstoffe reproduziert, sowie ein daraus resultierendes verbessertes Überleben in ECM- empfänglichen Mäusen festgestellt werden. Zusammenfassend lässt sich herausstellen, dass der Nachweis eines partiellen Impfschutzes gegen Plasmodium GPI induzierte ECM durch synthetische GPI Vakzine gelungen ist

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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