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Providing laypeople with results from dynamic infectious disease modelling studies affects their allocation preference for scarce medical resources—a factorial experiment
No full textBackground: Allocation of scarce medical resources can be based on different principles. It has not yet been investigated which allocation schemes are preferred by medical laypeople in a particular situation of medical scarcity like an emerging infectious disease and how the choices are affected by providing information about expected population-level effects of the allocation scheme based on modelling studies. We investigated the potential benefit of strategic communication of infectious disease modelling results. Methods: In a two-way factorial experiment (n = 878 participants), we investigated if prognosis of the disease or information about expected effects on mortality at population-level (based on dynamic infectious disease modelling studies) influenced the choice of preferred allocation schemes for prevention and treatment of an unspecified sexually transmitted infection. A qualitative analysis of the reasons for choosing specific allocation schemes supplements our results. Results: Presence of the factor "information about the population-level effects of the allocation scheme" substantially increased the probability of choosing a resource allocation system that minimized overall harm among the population, while prognosis did not affect allocation choices. The main reasons for choosing an allocation scheme differed among schemes, but did not differ among those who received additional model-based information on expected population-level effects and those who did not. Conclusions: Providing information on the expected population-level effects from dynamic infectious disease modelling studies resulted in a substantially different choice of allocation schemes. This finding supports the importance of incorporating model-based information in decision-making processes and communication strategies
Radiation Therapy in the German Hodgkin Study Group HD 16 and HD 17 Trials: Quality Assurance and Dosimetric Analysis for Hodgkin Lymphoma in the Modern Era
No full textPurpose: Radiation therapy (RT) is an integral part of treatment concepts for early-stage Hodgkin lymphoma. This analysis reports on RT quality in the recent HD16 and 17 trials of the German Hodgkin Study Group (GHSG). Methods and Materials: All RT plans of involved-node radiation therapy (INRT) in HD 17 were requested for analysis, along with 100 and 50 involved-field radiation therapy (IFRT) plans in HD 16 and 17, respectively. A structured assessment regarding field design and protocol adherence was performed by the reference radiation oncology panel of the GHSG. Results: Overall, 100 (HD 16) and 176 (HD 17) patients were eligible for analysis. In HD 16, 84% of RT series were evaluated as correct, with significant improvement compared with the predecessor studies (P < .001). In HD 17, 76.1% of INRT cases revealed a correct RT design compared with 69.0% of IFRT-cases, which was superior to previous studies (P < .001). Comparing INRT and IFRT, we found no significant differences in the percentage of any deviation (P = .418) or major deviations (P = .466). Regarding dosimetry, INRT was accompanied by an improvement in thyroid doses. Comparing different RT techniques, we found that intensity-modulated RT showed a reduction of high doses in the lung at the expense of an increased low-dose exposure in HD 17. Conclusions: The latest study generation of the GHSG demonstrates an improved quality in RT. A modern INRT design could be established without deterioration in quality. On a conceptual level, an individual consideration of the appropriate RT technique has to be performed
Success factors of academic journals in the digital age
No full textSince the early 1990s, when digitalisation began to open new opportunities for disseminating information, many academic journals started to introduce online services. However, while some studies suggest that online availability and free access to journal articles are positively connected to the number of citations an article receives, little is known about whether being an early adopter of digital services provides journals with a (long-term) competitive advantage in times of digital change. We use data from SSCI-listed management journals to examine which journals pioneered the introduction of digital services, to what extent first-mover advantages can be identified, and which journal characteristics are associated with citation-based performance indicators. Our results show that lower ranked journals were the first to introduce digital services and were beneficiaries of the digital age. Furthermore, we find a negative correlation between general submission fees and journal performance and that the top-performing journals of our sample are those of non-commercial publishers. Our analysis of the relationship between journal performance and the provision of open access contradicts previous studies, as we find no positive correlations between performance and open access on the journal level
The Anthelmintic Quassinoids Ailanthone and Bruceine a Induce Infertility in the Model Organism Caenorhabditis elegans by an Apoptosis-like Mechanism Induced in Gonadal and Spermathecal Tissues
No full textIn continuation of the search for new anthelmintic natural products, the study at hand investigated the nematicidal effects of the two naturally occurring quassinoids ailanthone and bruceine A against the reproductive system of the model nematode 'Caenorhabditis elegans' to pinpoint their anthelmintic mode of action by the application of various microscopic techniques. Differential Interference Contrast (DIC) and the epifluorescence microscopy experiments used in the presented study indicated the genotoxic effects of the tested quassinoids (c ailanthone = 50 µM, c bruceine A = 100 µM) against the nuclei of the investigated gonadal and spermathecal tissues, leaving other morphological key features such as enterocytes or body wall muscle cells unimpaired. In order to gain nanoscopic insight into the morphology of the gonads as well as the considerably smaller spermathecae of 'C. elegans', an innovative protocol of polyethylene glycol embedding, ultra-sectioning, acridine orange staining, tissue identification by epifluorescence, and subsequent AFM-based ultrastructural data acquisition was applied. This sequence allowed the facile and fast assessment of the impact of quassinoid treatment not only on the gonadal but also on the considerably smaller spermathecal tissues of 'C. elegans'. These first-time ultrastructural investigations on 'C. elegans' gonads and spermathecae by AFM led to the identification of specific quassinoid-induced alterations to the nuclei of the reproductive tissues (e.g., highly condensed chromatin, impaired nuclear membrane morphology, as well as altered nucleolus morphology), altogether implying an apoptosis-like effect of ailanthone and bruceine A on the reproductive tissues of 'C. elegans'
The Position of the Virtual Hinge Axis in Relation to the Maxilla in Digital Orthognathic Surgery Planning—A k-Means Cluster Analysis
No full textThe aim of this study was to investigate a possible relation between skeletal phenotypes and virtual mounting data in orthognathic surgery patients. A retrospective cohort study including 323 female (26.1 ± 8.7 years) and 191 male (27.9 ± 8.3 years) orthognathic surgery patients was conducted. A k-means cluster analysis was performed on the mounting parameters: the angle 𝛼 between the upper occlusal plane (uOP) and the axis orbital plane (AOP); the perpendicular distance (AxV) from the uOP to the hinge axis; and the horizontal length (AxH) of the uOP from upper incisor edge to AxV, with subsequent statistical analysis of related cepalometric values. Three clusters of mounting data were identified, representing three skeletal phenotypes: (1) balanced face with marginal skeletal class II or III and 𝛼=8∘, AxV = 36 mm and AxH = 99 mm; (2) vertical face with skeletal class II and 𝛼=11∘, AxV = 27 mm and AxH = 88 mm; (3) horizontal face with class III and 𝛼=2∘, AxV = 36 mm and AxH = 86 mm. The obtained data on the position of the hinge axis can be applied to any digital planning in orthognathic surgery using CBCT or a virtual articulator, provided that the case can be clearly assigned to one of the calculated clusters
The Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor Empagliflozin Reverses Hyperglycemia-Induced Monocyte and Endothelial Dysfunction Primarily through Glucose Transport-Independent but Redox-Dependent Mechanisms
No full textPurpose: Hyperglycaemia-induced oxidative stress and inflammation contribute to vascular cell dysfunction and subsequent cardiovascular events in T2DM. Selective sodium-glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin significantly improves cardiovascular mortality in T2DM patients (EMPA-REG trial). Since SGLT-2 is known to be expressed on cells other than the kidney cells, we investigated the potential ability of empagliflozin to regulate glucose transport and alleviate hyperglycaemia-induced dysfunction of these cells. Methods: Primary human monocytes were isolated from the peripheral blood of T2DM patients and healthy individuals. Primary human umbilical vein endothelial cells (HUVECs) and primary human coronary artery endothelial cells (HCAECs), and fetoplacental endothelial cells (HPECs) were used as the EC model cells. Cells were exposed to hyperglycaemic conditions in vitro in 40 ng/mL or 100 ng/mL empagliflozin. The expression levels of the relevant molecules were analysed by RT-qPCR and confirmed by FACS. Glucose uptake assays were carried out with a fluorescent derivative of glucose, 2-NBDG. Reactive oxygen species (ROS) accumulation was measured using the H2DFFDA method. Monocyte and endothelial cell chemotaxis were measured using modified Boyden chamber assays. Results: Both primary human monocytes and endothelial cells express SGLT-2. Hyperglycaemic conditions did not significantly alter the SGLT-2 levels in monocytes and ECs in vitro or in T2DM conditions. Glucose uptake assays carried out in the presence of GLUT inhibitors revealed that SGLT-2 inhibition very mildly, but not significantly, suppressed glucose uptake by monocytes and endothelial cells. However, we detected the significant suppression of hyperglycaemia-induced ROS accumulation in monocytes and ECs when empagliflozin was used to inhibit SGLT-2 function. Hyperglycaemic monocytes and endothelial cells readily exhibited impaired chemotaxis behaviour. The co-treatment with empagliflozin reversed the PlGF-1 resistance phenotype of hyperglycaemic monocytes. Similarly, the blunted VEGF-A responses of hyperglycaemic ECs were also restored by empagliflozin, which could be attributed to the restoration of the VEGFR-2 receptor levels on the EC surface. The induction of oxidative stress completely recapitulated most of the aberrant phenotypes exhibited by hyperglycaemic monocytes and endothelial cells, and a general antioxidant N-acetyl-L-cysteine (NAC) was able to mimic the effects of empagliflozin. Conclusions: This study provides data indicating the beneficial role of empagliflozin in reversing hyperglycaemia-induced vascular cell dysfunction. Even though both monocytes and endothelial cells express functional SGLT-2, SGLT-2 is not the primary glucose transporter in these cells. Therefore, it seems likely that empagliflozin does not directly prevent hyperglycaemia-mediated enhanced glucotoxicity in these cells by inhibiting glucose uptake. We identified the reduction of oxidative stress by empagliflozin as a primary reason for the improved function of monocytes and endothelial cells in hyperglycaemic conditions. In conclusion, empagliflozin reverses vascular cell dysfunction independent of glucose transport but could partially contribute to its beneficial cardiovascular effects
Towards Data Analytics-Driven Supply Chain Performance Measurement Systems:Development of a conceptual framework and a supportive guideline for the adoption of Data Analytics in Supply Chain Performance Measurement Systems
No full textIn der heutigen, äußerst wettbewerbsintensiven und dynamischen Geschäftswelt sind effiziente und effektive Lieferketten unerlässlich. Data analytics liefern datenbasierte Erkenntnisse, die eine effiziente Entscheidungsfindung ermöglichen. Gleichzeitig spielen Supply Chain Performance Measurement Systems (SCPMSs) eine zentrale Rolle bei der Effektivitätsmessung und -erreichung. Diese Dissertation führt eine umfassende Studie zum Zusammenspiel von data analytics und SCPMSs durch, mit dem Fokus auf Einblicke aus Forschung und Praxis. Dabei werden unterstützende Instrumente entwickelt, die das volle Potenzial eines data analytics-driven SCPMS aufzeigen. Die Forschung resultiert in einem prägnanten konzeptionellen Modell und praktischen Richtlinien, um Forschende und Praktiker bei der Gestaltung, Implementierung und Nutzung von data analytics-driven SCPMSs in verschiedenen Bereichen der Lieferketten zu unterstützen.In an intensely competitive and dynamic business landscape, supply chains are required to be efficient and effective. Data analytics is seen as an enabler in this pursuit, offering data-driven insights that steer efficient decision-making. Simultaneously, Supply Chain Performance Measurement Systems (SCPMSs) play a vital role in measuring and achieving effectiveness. This thesis reports a comprehensive study on the synergistic interplay between data analytics and SCPMSs, focusing on gathering insights from both research and practice and developing supportive artifacts that disclose the full potential of a data analytics-driven SCPMS. This research resulted in a concise conceptual framework and a practical guideline to support scholars and practitioners in navigating the research, design, implementation, and utilization of data analytics-driven SCPMSs across diverse supply chain areas
Transatlantic Archives and Transatlantic Literary Studies
No full textDer Beitrag beschreibt schlaglichtartig die historische Entwicklung sowie die gegenwärtigen Herausforderungen der Archivierung literarischer Handschriften im globalen Kontext. Ein besonderer Schwerpunkt liegt dabei auf den Wechselwirkungen zwischen der Institution Literaturarchiv einerseits und der transatlantischen Literaturwissenschaft und -geschichte andererseits. Durch ihre konkreten historischen und geographischen Entstehungszusammenhänge und ihre materielle Unikalität sind Manuskripte in nicht unerheblichem Maß lokal determiniert und an nationalkulturelle Narrative gekoppelt, werden aber als Resultat von Entwicklungen des 20. Jahrhunderts (wie z.B. der Exilierung und Vertreibung von Autor:innen im Kontext europäischer Totalitarismen oder der Herausbildung eines internationalen Markts für schriftstellerische Papiere in der zweiten Hälfte des Jahrhunderts) zunehmend disloziert und als von universalem Wert beschrieben. Der Beitrag spürt diesen Themen unter anderem am Beispiel Thomas Manns und seiner amerikanischen Archivgeschichte nach. Den Abschluss bilden einige Überlegungen zu (Literatur-)Archiven und Digitalisierung, insbesondere im Kontext der Corona-Pandemie.The contribution describes aspects of the historical development of, and the contemporary challenges faced by, the archiving of literary manuscripts in a global context. It focuses more specifically on the relationship between the literary archive as an institution, on the one hand, and transatlantic literary studies and literary history, on the other. Manuscripts are to a significant extent marked as local and described as national in terms of their historical and geographical genesis and their material uniqueness, but they have increasingly come to be seen as deterritorialized and universal as the result of twentieth-century developments (phenomena which include the exile and enforced migration of authors in the context of European totalitarian regimes or the rise of an international marketplace for literary papers over the course of the second half of the century). One of the key examples through which the contribution traces these themes is Thomas Mann and the history of his American archiving. The conclusion offers reflections on (literary) archives and digitization, in particular in the context of the global pandemic
Transcriptome analyses in infertile men reveal germ cell–specific expression and splicing patterns
No full textThe process of spermatogenesis—when germ cells differentiate into sperm—is tightly regulated, and misregulation in gene expression is likely to be involved in the physiopathology of male infertility. The testis is one of the most transcriptionally rich tissues; nevertheless, the specific gene expression changes occurring during spermatogenesis are not fully understood. To better understand gene expression during spermatogenesis, we generated germ cell–specific whole transcriptome profiles by systematically comparing testicular transcriptomes from tissues in which spermatogenesis is arrested at successive steps of germ cell differentiation. In these comparisons, we found thousands of differentially expressed genes between successive germ cell types of infertility patients. We demonstrate our analyses’ potential to identify novel highly germ cell–specific markers (TSPY4 and LUZP4 for spermatogonia; HMGB4 for round spermatids) and identified putatively misregulated genes in male infertility ('RWDD2A, CCDC183, CNNM1, SERF1B'). Apart from these, we found thousands of genes showing germ cell–specific isoforms (including 'SOX15, SPATA4, SYCP3, MKI67'). Our approach and dataset can help elucidate genetic and transcriptional causes for male infertility