Separation and characterization of subpopulations of biopharmaceuticals

The chemical changes that cause heterogeneity in protein therapeutics are well described and monitored during development and manufacturing. Many of these subpopulations were investigated regarding their impact on the therapeutic protein function. Adjustments in processes, formulation and protein engineering are applied to mitigate the number and quantity of protein variants. Yet, the root cause for the formation of protein subpopulations can not be controlled considering the manifold influences that lead to chemical changes. Therefore, it is important to know the impact of each variant on the stability of the protein drug. However, little is known about the impact of each subpopulation on protein stability, self-interaction, interaction with other variants or aggregation propensity. This thesis aims to separate, characterize and identify potential aggregation prone protein variants. If such variants are identified, further investigations are conducted to determine the influence of the variants on the stability of the therapeutic agent. With this work we aim to develop a tool kit of methods to gain knowledge about aggregation prone variants. A prerequisite for all methods is the maintenance of the intact protein variant in order to avoid any changes that might alter the protein behavior. Our tools include the separation and collection of individual subpopulations in their native state and analytical methods suitable for the limited quantities of sample. In the future, these applications and the knowledge gained from them can be used to remove or stabilize critical variants as a step towards protein therapeutics with increased stability and safety

Confronting the Bullies, Comforting the Victim, or Reporting to University Staff? Prosocial Intentions Towards Social Exclusion in University Students.

Social exclusion as a form of in-person relational bullying in higher education (HE) leads to loneliness in students and puts their mental well-being at risk. Utilising and extending the theory of planned behaviour (TPB), we investigated prosocial intentions towards bullying in HE students. We included empathic concern and anticipated regret to potentially explain differences in three behavioural intentions towards bullying: comforting the victim, confronting the bullies, and reporting the bullying to the university. The sample comprised 419 participants in an online sample from the UK (MAge = 22.76 years, SDAge = 4.02 years; 47.0% male, 50.6% female, 2.4% other) who filled in a digital questionnaire consisting of a short vignette describing an in-person situation of relational bullying. Applying structural equation modelling, we examined the three prosocial behavioural intentions towards bullying as outcome variables in two models while controlling for age, gender, and socially desirable responding. Traditional TPB predictors were positively associated with confronting the bullies. Empathic concern and anticipated regret were positively associated with comforting the victim. These results demonstrate how cognitive and emotional predictors uniquely contribute to prosocial intentions towards bullying among students. We discuss practical implications for the design of anti-bullying strategies in HE.publishedVersio

Systematic Comparison of Methods in Threat and Risk Analysis of ICT Security in Industry 4.0

Industry 4.0 is the connection of intelligent objects with information technology and thus with the internet. This leads to new fields of application in information technology. To protect intelligent objects security approaches are necessary. Several security standards already exist for ICT, but not for Industry 4.0. The present paper considers standards to conduct threat analysis and risk analysis of ICT security based on a literature review. A catalogue of criteria relevant to such standards for Industry 4.0 is developed which serves as the basis of their evaluation. Thirteen standards are identified as relevant regarding the criteria, among them IT-Grundschutz

Gamified Feedback in Electronic Negotiation Training

Negotiations are a relevant and highly complex business skill. Therefore, extensive training is required to become a good negotiator. Such training is offered by universities for their students and by companies for their employees. The present paper designs gamified feedback features in electronic negotiation training and evaluates their potential and their effects. Following a design science research method, feedback mechanisms in electronic negotiation training are derived from literature. An assessment regarding their relevance for e-negotiation training shows a preparation quiz, set and track goals and expert reviews to be the most useful gamified feedback mechanisms. Dedicated mock-ups implementing these feedback mechanisms are designed and evaluated in semi-structured interviews showing their capability to improve relevant negotiation skills, as well as motivation and competence of the learners. Out of the three mock-ups, the interviewees prefer the feedback mechanisms “expert review” and “set and track goals”; both mechanisms provide a competence-confirming learning experience and an autonomous learning experience

Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis

Aim Thrombolytic therapy induces faster clot dissolution than anticoagulation in patients with acute pulmonary embolism (PE) but is associated with an increased risk of haemorrhage. We reviewed the risks and benefits of thrombolytic therapy in the management of patients with acute PE. Methods and results We systematically reviewed randomized controlled studies comparing systemic thrombolytic therapy plus anticoagulation with anticoagulation alone in patients with acute PE. Fifteen trials involving 2057 patients were included in our meta-analysis. Compared with heparin, thrombolytic therapy was associated with a significant reduction of overall mortality (OR; 0.59, 95% CI: 0.36-0.96). This reduction was not statistically significant after exclusion of studies including high-risk PE (OR; 0.64, 95% CI: 0.35-1.17). Thrombolytic therapy was associated with a significant reduction in the combined endpoint of death or treatment escalation (OR: 0.34, 95% CI: 0.22-0.53), PE-related mortality (OR: 0.29; 95% CI: 0.14-0.60) and PE recurrence (OR: 0.50; 95% CI: 0.27-0.94). Major haemorrhage (OR; 2.91, 95% CI: 1.95-4.36) and fatal or intracranial bleeding (OR: 3.18, 95% CI: 1.25-8.11) were significantly more frequent among patients receiving thrombolysis. Conclusions Thrombolytic therapy reduces total mortality, PE recurrence, and PE-related mortality in patients with acute PE. The decrease in overall mortality is, however, not significant in haemodynamically stable patients with acute PE. Thrombolytic therapy is associated with an increase of major and fatal or intracranial haemorrhag

Interdisciplinary, but how? Anthropological Perspectives from Collaborative Research on Climate and Environmental Change

The aim of this perspective article is to rethink how anthropology can be involved in interdisciplinary research on climate and environmental change, considering wide-spread obstacles for successful collaboration and recommending best practices. Anthropologists complement ”big data“ with “thick data“, which must not be overlooked if the global scientific goal is to have a sustainable and responsible local impact in communities facing environmental change. Anthropologists are used to working with uncertainty, qualified for shifting scales and perspectives, and, perhaps most importantly, pre-occupied with studying the human dimensions of environmental change. However, there are still many practical, ontological and epistemological challenges concerning interdisciplinary research with an environmental focus. After outlining the most recent developments and literature on interdisciplinary research, we share our experience with integrating diverse forms of environmental knowledge including local and indigenous knowledge. Using an inductive approach, we build on and illustrate our conclusions with ethnographic vignettes that stem from a variety of our interdisciplinary projects. Several key themes and suggestions emerge: a) establishment of a joint epistemological framework before the research phase; b) humility and respect for methodologies used by other disciplines, including time spent on studying these with colleagues of different disciplinary backgrounds; c) openness, creativity and flexibility to step out of one's own disciplinary comfort zone; d) communication within the project team based on trust and without disciplinary hierarchies. Finally, we share some practical suggestions on how to set up interdisciplinary projects.</p

Succumbing to the Call of Violence – Sex-Linked Development of Appetitive Aggression in Relation to Familial and Organized Violence

Appetitive aggression is the attraction to violent behavior, which can peak in the experience of a combat high. In various war and conflict scenarios, members of armed groups have reported developing a desire to hunt and even kill humans. More recently, we reported that the phenomenon has also been observed in female ex-combatants with varying participation in warfare. Despite recent investigations on risk factors for appetitive aggression, sex-specific pathways in the development of appetitive aggression have not yet been delineated. This study investigated moderation effects of sex on previously identified risk factors for appetitive aggression by means of regression analyses in a sample of individuals with varying degrees of warfare participation (overall sample, n = 602). First examining a sample characterized by backgrounds heterogeneous in both sociodemographic data and war experiences, the analysis was then replicated in a subsample of fighters active during the civil war (combatant sample, n = 109). In both samples, regression analyses revealed significant moderation effects of sex. Childhood maltreatment and traumatic events had positive associations on the development of appetitive aggression for males but a negative (childhood maltreatment) or no (traumatic events) association for females. Perpetrated events were more strongly correlated with appetitive aggression for females than for males. This pattern was pronounced for the combatant sample. These results are in favor of sex-linked pathways. In both sexes, appetitive aggression may have evolved as a biologically prepared response to cruel environments but might develop along different trajectories. The current study highlights the need for addressing appetitive aggression in order to support peace-building processes and emphasizes sex specific starting-points

Single-exposure X-ray phase imaging microscopy with a grating interferometer

The advent of hard X-ray free-electron lasers enables nanoscopic X-ray imaging with sub-picosecond temporal resolution. X-ray grating interferometry offers a phase-sensitive full-field imaging technique where the phase retrieval can be carried out from a single exposure alone. Thus, the method is attractive for imaging applications at X-ray free-electron lasers where intrinsic pulse-to-pulse fluctuations pose a major challenge. In this work, the single-exposure phase imaging capabilities of grating interferometry are characterized by an implementation at the I13-1 beamline of Diamond Light Source (Oxfordshire, UK). For comparison purposes, propagation-based phase contrast imaging was also performed at the same instrument. The characterization is carried out in terms of the quantitativeness and the contrast-to-noise ratio of the phase reconstructions as well as via the achievable spatial resolution. By using a statistical image reconstruction scheme, previous limitations of grating interferometry regarding the spatial resolution can be mitigated as well as the experimental applicability of the technique

Competition Reduces Response Times in Multiparty Conversation

Natural conversations are characterized by short transition times between turns. This holds in particular for multi-party conversations. The short turn transitions in everyday conversations contrast sharply with the much longer speech onset latencies observed in laboratory studies where speakers respond to spoken utterances. There are many factors that facilitate speech production in conversational compared to laboratory settings. Here we highlight one of them, the impact of competition for turns. In multi-party conversations, speakers often compete for turns. In quantitative corpus analyses of multi-party conversation, the fastest response determines the recorded turn transition time. In contrast, in dyadic conversations such competition for turns is much less likely to arise, and in laboratory experiments with individual participants it does not arise at all. Therefore, all responses tend to be recorded. Thus, competition for turns may reduce the recorded mean turn transition times in multi-party conversations for a simple statistical reason: slow responses are not included in the means. We report two studies illustrating this point. We first report the results of simulations showing how much the response times in a laboratory experiment would be reduced if, for each trial, instead of recording all responses, only the fastest responses of several participants responding independently on the trial were recorded. We then present results from a quantitative corpus analysis comparing turn transition times in dyadic and triadic conversations. There was no significant group size effect in question-response transition times, where the present speaker often selects the next one, thus reducing competition between speakers. But, as predicted, triads showed shorter turn transition times than dyads for the remaining turn transitions, where competition for the floor was more likely to arise. Together, these data show that turn transition times in conversation should be interpreted in the context of group size, turn transition type, and social setting

Severe, very early onset preeclampsia in a Covid 19-positive woman with a twin pregnancy presenting with a hydatidiform mole and coexisting normal fetus: a case report

Cases of hydatidiform moles with a coexisting fetus are sparse and patients are at high risk for severe complications. Patients and physicians often face the dilemma of the wish to continue pregnancy until viability of the fetus while the risk for maternal complications increases. We present an educational case of a twin pregnancy presenting with a hydatidiform mole and coexisting normal fetus with a placenta praevia. The patient developed severe, early onset preeclampsia with beginning HELLP-syndrome and was tested Covid-19 positive in the further course. Termination of pregnancy was conducted via caesarean section at 18 + 6 weeks of pregnancy. Histopathology and genetic analysis confirmed a complete hydatidiform mole next to a normal placenta. Close follow-up examinations were conducted and showed normal findings including ß HCG levels normalizing within 5 months. This case combines several rare, difficult and severe medical conditions and demonstrates how an individualized therapy by an interdisciplinary team covering a highly sensitive topic was developed in a situation where no guidelines exist