Predictive Tools in Protein Chromatography: Extension and Optimization of a Molecular Modeling Approach

The aim of this study was to increase the understanding of the binding behavior of biomolecules on different adsorbents. This ought to be used for prediction and problem analysis. The approach was to develop a molecular dynamics simulations tool, which represents both: the biomolecule and the ligand surface at the atomic level and realistically maps the interaction processes between them. Results were validated by corresponding laboratory experiments

College newspapers - watchdogs or lapdogs?

Diese Diplomarbeit behandelt amerikanische College-Zeitungen und deren Status und Funktionen für die Campus-Gemeinde. Das Forschungsinteresse beinhaltet neben den Funktionen auch die Verbindung zur jeweiligen Universität, ebenso wie das Selbstverständnis von College-Zeitungen bzw. deren ChefredakteurInnen. Dafür werden der Begriffe der Unabhängigkeit und die Kritik- und Kontrollfunktion dieser Medien genauer untersucht. In diesem Zusammenhang ist auch das Konzept des journalistischen „Watchdogs“ von Bedeutung. Abschließend sollen die Probleme dieser Medien in Bezug auf die Verbindung zur Universität und in Bezug auf kritische Berichterstattung allgemein erhoben werden, sowie der Status von College-Zeitungen als Ausbildungsstätten für JournalistInnen und als regionale Medien. Die Untersuchung wurde vor dem theoretischen Hintergrund von Luhmanns Theorie sozialer Systeme sowie der Funktionen der Massenmedien durchgeführt. Weitere wichtige Konzepte waren jenes des journalistischen Watchdogs nach Lance W. Bennett und William Serrin, sowie Ansätze aus der internen Unternehmenskommunikation. Weiters wurde der historische und rechtliche Hintergrund von US-amerikanischen College-Zeitungen erarbeitet. Dies beinhaltet einen kurzen Überblick über Gesetze im Zusammenhang mit Presse- und Recherchefreiheit sowie die wichtigsten Präzedenzfälle. Außerdem wurde die Geschichte amerikanischer College-Medien sowie die Geschichte der JournalistInnenausbildung in zwei Kapiteln näher betrachtet. Methodisch wurde ein Methodenmix aus einer quantitativen Inhaltsanalyse und zehn qualitativen ExpertInneninterviews mit ChefredakteurInnen von College-Zeitungen durchgeführt. Die Stichprobe beinhaltete zehn Tageszeitungen an öffentlichen und privaten Universitäten und Colleges in fünf Staaten im Nordosten in den USA. Die Inhaltsanalyse ergab Daten über das Themenspektrum von College-Zeitungen sowie über den Stellenwert von kritischen Artikeln im Vergleich zur sogenannten „Hofberichterstattung“. Die ExpertInneninterviews behandelten Fragen zur Unabhängigkeit der Zeitungen, deren Status und Selbstbild sowie zu den Problemen, mit denen die studentischen ChefredakteurInnen in ihrem Arbeitsalltag konfrontiert werden, beispielsweise betreffend der Doppelrolle als StudierendeR und JournalistIn. Weiters wurde der Stellenwert der betreffenden Medien als Institutionen für JournalistInnenausbildung sowie als regionale Zeitungen erfragt. Die Studie brachte als Ergebnis, dass, obwohl nicht alle Zeitungen finanziell und inhaltlich unabhängig von ihrer Universität waren, alle ChefredakteurInnen angaben, nach der höchstmöglichen Unabhängigkeit zu streben. KeineR der Befragten gab an, sich von der Universität kontrolliert oder unter Druck gesetzt zu fühlen. Obwohl nicht alle Zeitungen eine gute Beziehung zur jeweiligen Universität haben, besonders was kritische Themen betrifft, gaben die ChefredakteurInnen an, dass kritische Berichterstattung generell möglich sei. Darüber hinaus wurde festgestellt, dass College-Zeitungen die gleichen Funktionen erfüllen wie professionelle Tageszeitungen. Die einzigen Unterschiede waren das unterschiedliche Themenspektrum (mit einem Schwerpunkt auf Sportberichterstattung, welcher auf die spezielle Zielgruppe zurückzuführen war), sowie der große Stellenwert der Ausbildungsfunktion. College-JournalistInnen verbringen einen Großteil ihrer Arbeitszeit mit der Ausbildung junger ReporterInnen, da sie Ausbildung als eine der wichtigsten Funktionen betrachten. Darüber hinaus erfüllen College- Medien auch die Funktionen interner Unternehmenskommunikation, selbst wenn sie nicht von der Universitätsleitung unabhängig sind. Die Inhaltsanalyse ergab, dass nur ein sehr geringer Prozentsatz (3.6 %) der Artikel in der Stichprobe als \Hofberichterstattung" identifiziert werden konnte, wohingegen etwa ein Fünftel aller Artikel als kritisch codiert wurde. Alle Chefredakteurinnen gaben an, es als ihre Verantwortung zu sehen, kritisch zu berichten, die Universität und ihre Handlungen zu kontrollieren und im besten Interesse der Studierenden zu handeln. Es gebe kein anderes Medium, das sich den Interessen dieser Gemeinschaf annehme und sich für Ereignisse an Universitäten und Colleges in diesem Ausmaß interessiere, weshalb auch die Watchdog-Role sehr ernst genommen wird. Gleichzeitig gaben die ExpertInnen an, dass es manchmal schwer sei, kritisch zu berichten, weil man sich der Hochschule eng verbunden fühle und loyal sein müsse. Weitere Hindernisse für kritische Berichterstattung seien laut den ExpertInnen die Unerfahrenheit und Unsicherheit der ReporterInnen, sowie mangelnde Kooperation von Seiten der Universität. An manchen Universitäten sind MitarbeiterInnen dazu angehalten, nicht mit Studierenden-Reportern zu sprechen und sie an die PR-Abteilung zu verweisen. Im Großen und Ganzen allerdings strebten alle ExpertInnen danach, die Watchdog-Funktion ihrer Zeitung bestmöglich zu erfüllen, obwohl dies je nach College unterschiedlich einfach sein dürfte. Abschließend sei zu sagen, dass College-Zeitungen weder als Watchdog noch als „Lapdog“, als Schoßhund der Universität bezeichnet werden können. Viele beschränken sich dadurch selbst, loyal zu ihrer Hochschule sein zu wollen. Jedoch war das Ergebnis deutlich anders, die Zeitungen deutlich kritischer als es nach der Ausarbeitung der Geschichte und der rechtlichen Situation zu erwarten war.The aim of this thesis is to treat college newspapers in the United States and their status and functions on campus. The research interest covers the role of college newspapers as well as their connection to their host-institutions. Furthermore, additional points of interest included self-perception, independence, and the role as a controlling instance and watchdog for the campus community. To conclude, the problems of college newspapers concerning their relationship to the university and the possibility of critical reporting in college publications as well as their role as local newspapers and as institutions for journalism education should be further clarified. The empirical study was conducted upon the theoretical background of Niklas Luhmann's theory of social systems along with the functions of mass media and the concept of the journalistic watchdog according to Lance W. Bennett and William Serrin. A further theoretical implication treats different concepts of internal communication. Furthermore, the historic and legal backgrounds of college newspapers in the United States were reviewed for this thesis. This includes a short overview about freedom of information laws and legal precedents concerning college publications as well as the history of these media and an introduction to journalism education in the United States. The methodological approach was composed of a quantitative content analysis of a sample of ten college daily newspapers in conjunction with qualitative interviews with ten editors in chief. The sample included daily newspapers at public and private institutions in five different states in the north-east of the United States. The study showed that even though not all newspapers in the sample can be considered financially and editorially independent, they all strive for the highest degree of independence possible. None of the editors in chief felt pressured or controlled by their host-institutions. Despite the fact that not all newspapers claimed to have a good relationship to their universities, especially when it came to newsgathering about critical topics, all interviewees felt critical journalism was possible and necessary within their publications. Generally it can be said that student newspapers fulfill the same functions as professional publications. Nevertheless, two major differences to professional newspapers were encountered: the different content with a strong focus on sports reporting (due to the disparate target group) and an important educational purpose fulfilled by college publications. Student journalists generally spend much more time on training fledgling reporters than professional journalists. The interviewees considered the education of young reporters as one of the main functions of collegiate newspapers. In addition to this, these publications also have a special status as means for internal communication for the university. This was the reason why the question whether college newspapers are the watchdogs or the lapdogs of their host-institutions became especially interesting. The content analysis revealed that only a small percentage (3.6 %) of the articles could be considered obsequious, whereas approximately one fifth of the articles in the sample was coded as critical. All editors in chief felt responsible for the student community which was the reason why critical reporting was considered a major task of college newspapers. No other media outlet overviews the decisions of colleges and universities in the way that student newspapers are able to do so. Therefore, the interviewees felt obliged to fulfill the watchdog role properly and to look after the best interests of the student body. At the same time, they felt that forming a community and praising the university when they deserved it was a duty of every college newspaper. For this reason, critical reporting is not always an easy thing to do for student writers, since their loyalty may be pulled in different directions when it comes to depreciative topics. Other stumbling blocks for critical journalism encountered by the interviewees were the inexperience of the reporters along with the difficulties in newsgathering due to a lack of cooperation of the administration. At some universities employees are not supposed to talk to student reporters at all, but to refer them to the public relations department for all further information. This makes it difficult for student journalists to get information that is not PR. Generally speaking though, most newspapers strive for the best possible fulfillment of the watchdog role, even though this might be easier at some colleges than at others. The conclusion is that college newspapers are more watchdogs than lapdogs of their respective universities. Even though they may in some situations be afraid to bark, the newspapers analyzed within this thesis were much more critical than expected

Cost-effectiveness of nicotine replacement therapy in patients with chronic obstructive pulmonary disease

HINTERGRUND Die chronisch-obstruktive Lungenerkrankung (COPD) ist charakterisiert durch eine fortschreitende Verengung der Atemwege und daraus resultierende verminderte Lungenfunktion. COPD ist weltweit die vierthäufigste Todesursache mit stark steigender Tendenz. Rauchen ist dabei der am leichtesten zu vermeidende Risikofaktor. Innerhalb der zugrunde liegenden Arbeit wird die Kosteneffektivität einer Raucherentwöhnung mit Nikotinersatztherapie (NET) gegen eine Raucherentwöhnung ohne NET bei Patienten mit COPD im Hinblick auf gewonnene Lebensjahre untersucht. METHODEN Mit Hilfe eines Markov-Modells wird der natürliche Verlauf der Erkrankung in einem Langzeitszenario simuliert, um den Effekt einer Raucherentwöhnung mit NET gegen eine Raucherentwöhnung ohne NET aus der Perspektive der gesetzlichen Krankenkassen abbilden zu können. Den verwendeten Modelldaten wie z.B. individuelle Übertrittswahrscheinlichkeiten zwischen einzelnen Schweregraden der COPD, Mortalität, Effektivität und Kosten der NET (Basisjahr 2008) basieren auf diversen systematischen Literaturrecherchen sowie eigenen Berechnungen. Im Ergebnis liefert die Analyse inkrementelle Kosten pro gerettetem Lebensjahr. Effekte und Kosten werden mit 3 % diskontiert, alle wichtigen Parameter in Sensitivitätsanalysen variiert. ERGEBNISSE Die Raucherentwöhnung mit NET bei COPD-Patienten ist der Raucherentwöhnung ohne NET hinsichtlich eingesparter Kosten und gewonnener Lebensjahre überlegen. Ein mit NET entwöhnter COPD-Patient verursacht in einer Zeitspanne von 55 Jahren Kosten in Höhe von 26.207 € (diskontiert) bei den gesetzlichen Krankenkassen und gewinnt 17,06 Lebensjahre (diskontiert). Ohne NET entwöhnte Patienten hingegen generieren Kosten in Höhe von 28.302 € (diskontiert) und gewinnen 16,65 Lebensjahre (diskontiert). Eine Raucherentwöhnung mit NET verursacht somit 2.095 € weniger Kosten und geht mit einem Gewinn an 0,61 Lebensjahren einher. SCHLUSSFOLGERUNG Die Raucherentwöhnung von COPD-Patienten mit NET ist die dominante Strategie verglichen mit keiner Intervention. Die Ergebnisse der Analyse sind robust gegenüber der Variation zahlreicher durchgeführter Sensitivitätsanalysen.INTRODUCTION: Chronic-obstructive pulmonary disease (COPD) is a respiratory disorder characterized by a progressive airway obstruction followed by a decrease in lung function. Tobacco smoking is considered as the most important avoidable risk factor. COPD is currently the fourth leading cause of death in world with a predictable future increase in prevalence and mortality. The presented decision-analytic model aims to analyze the incremental cost-effectiveness ratio (ICER) of smoking cessation with Nicotine Replacement Therapy (NRT) compared to smoking cessation without NRT in COPD patients. METHODS: A Markov-Model simulates the long-term natural course of disease con-sidering the effect of smoking cessation with NRT vs. no intervention from the per-spective of the German Statutory Health System. The input data such as transition probabilities between COPD severity levels, costs (base year 2008) and NRT effec-tiveness are based on several systematic literature researches and internal calcula-tions. As an outcome the incremental costs per life-year gained (LYG) are calculated. RESULTS: Within a simulated time horizon of 55 years, smoking cessation with NRT is the dominant strategy with 26207 € and 17.06 LYG (discounted). The comparative smoking cessation without NRT results in 2095 € additional costs and a loss of 0.61 LYG. NRT remains the dominant strategy in most of the performed sensitivity analyses. CONCLUSIONS: NRT is the dominant strategy compared to no intervention for smoking cessation in patients with COPD. The results of this analysis are robust to the variation of numerous model parameters and assumptions

Administration of Tramadol or Buprenorphine via the drinking water for post-operative analgesia in a mouse-osteotomy model

Adequate analgesia is essential whenever pain might occur in animal experiments. Unfortunately, the selection of suitable analgesics for mice in bone-linked models is limited. Here, we evaluated two analgesics - Tramadol [0.1 mg/ml (Tlow) vs. 1 mg/ml (Thigh)] and Buprenorphine (Bup; 0.009 mg/ml) - after a pre-surgical injection of Buprenorphine, in a mouse-osteotomy model. The aim of this study was to verify the efficacy of these opioids in alleviating pain-related behaviors, to provide evidence for adequate dosages and to examine potential side effects. High concentrations of Tramadol affected water intake, drinking frequency, food intake and body weight negatively in the first 2-3 days post-osteotomy, while home cage activity was comparable between all groups. General wellbeing parameters were strongly influenced by anesthesia and analgesics. Model-specific pain parameters did not indicate more effective pain relief at high concentrations of Tramadol. In addition, ex vivo high-resolution micro computed tomography (µCT) analysis and histology analyzing bone healing outcomes showed no differences between analgesic groups with respect to newly formed mineralized bone, cartilage and vessels. Our results show that high concentrations of Tramadol do not improve pain relief compared to low dosage Tramadol and Buprenorphine, but rather negatively affect animal wellbeing

Antibiotic resistance surveillance of Klebsiella pneumoniae complex is affected by refined MALDI-TOF identification, Swiss data, 2017 to 2022.

BackgroundModern laboratory methods such as next generation sequencing and MALDI-TOF allow identification of novel bacterial species. This can affect surveillance of infections and antimicrobial resistance. From 2017, increasing numbers of medical microbiology laboratories in Switzerland differentiated Klebsiella variicola from Klebsiella pneumoniae complex using updated MALDI-TOF databases, whereas many laboratories still report them as K. pneumoniae or K. pneumoniae complex.AimOur study explored whether separate reporting of K. variicola and the Klebsiella pneumoniae complex affected the ANRESIS surveillance database.MethodsWe analysed antibiotic susceptibility rates and specimen types of K. variicola and non-K. variicola-K. pneumoniae complex isolates reported by Swiss medical laboratories to the ANRESIS database (Swiss Centre for Antibiotic Resistance) from January 2017 to June 2022.ResultsAnalysis of Swiss antimicrobial resistance data revealed increased susceptibility rates of K. variicola compared with species of the K. pneumoniae complex other than K. variicola in all six antibiotic classes tested. This can lead to underestimated resistance rates of K. pneumoniae complex in laboratories that do not specifically identify K. variicola. Furthermore, K. variicola strains were significantly more often reported from blood and primarily sterile specimens than isolates of the K. pneumoniae complex other than K. variicola, indicating increased invasiveness of K. variicola.ConclusionOur data suggest that refined differentiation of the K. pneumoniae complex can improve our understanding of its taxonomy, susceptibility, epidemiology and clinical significance, thus providing more precise information to clinicians and epidemiologists

A systematic literature review of clinical trials and therapeutic applications of ibogaine

BACKGROUND Iboga and its primary alkaloids, ibogaine and noribogaine, have been of interest to researchers and practitioners, mainly due to their putative efficacy in treating substance use disorders (SUDs). For many SUDs, still no effective pharmacotherapies exist. Distinct psychoactive and somatic effects of the iboga alkaloids set them apart from classic hallucinogens like LSD, mescaline, and psilocybin. AIMS The study team performed this systematic review focusing on clinical data and therapeutic interventions involving ibogaine and noribogaine. METHODS The team conducted a search for all publications up to December 7, 2020, using PubMed and Embase following PRISMA guidelines. RESULTS In total, we identified 743 records. In this review, we consider 24 studies, which included 705 individuals receiving ibogaine or noribogaine. This review includes two randomized, double-blind, controlled clinical trials, one double-blind controlled clinical trial, 17 open-label studies or case series (including observational or retrospective studies), three case reports, and one retrospective survey. The published data suggest that ibogaine is an effective therapeutic intervention within the context of SUDs, reducing withdrawal symptoms and craving. Data also point toward a beneficial impact on depressive and trauma-related psychological symptoms. However, studies have reported severe medical complications and deaths, which seem to be associated with neuro- and cardiotoxic effects of ibogaine. Two of these fatalities were described in the 24 studies included in this review. CONCLUSION Treatment of SUDs and persisting comorbidities requires innovative treatment approaches. Rapid-onset therapies such as the application of ibogaine may offer novel treatment opportunities for specific individuals. Rigorous study designs within medical settings are necessary to warrant safe application, monitoring, and, possibly, medical intervention

Fast Diagnostics of BRAF Mutations in Biopsies from Malignant Melanoma

According to the American skin cancer foundation, there are more new cases of skin cancer than the combined incidence of cancers of the breast, prostate, lung, and colon each year, and malignant melanoma represents its deadliest form. About 50% of all cases are characterized by a particular mutation BRAFV600E in the BRAF (Rapid Acceleration of Fibrosarcoma gene B) gene. Recently developed highly specific drugs are able to fight BRAFV600E mutated tumors but require diagnostic tools for fast and reliable mutation detection to warrant treatment efficiency. We completed a preliminary clinical trial applying cantilever array sensors to demonstrate identification of a BRAFV600E single-point mutation using total RNA obtained from biopsies of metastatic melanoma of diverse sources (surgical material either frozen or fixated with formalin and embedded in paraffin). The method is faster than the standard Sanger or pyrosequencing methods and comparably sensitive as next-generation sequencing. Processing time from biopsy to diagnosis is below 1 day and does not require PCR amplification, sequencing, and labels

Impact of Janus Kinase Inhibition with Tofacitinib on Fundamental Processes of Bone Healing

Both inflammatory diseases like rheumatoid arthritis (RA) and anti-inflammatory treatment of RA with glucocorticoids (GCs) or non-steroidal anti-inflammatory drugs (NSAIDs) negatively influence bone metabolism and fracture healing. Janus kinase (JAK) inhibition with tofacitinib has been demonstrated to act as a potent anti-inflammatory therapeutic agent in the treatment of RA, but its impact on the fundamental processes of bone regeneration is currently controversially discussed and at least in part elusive. Therefore, in this study, we aimed to examine the effects of tofacitinib on processes of bone healing focusing on recruitment of human mesenchymal stromal cells (hMSCs) into the inflammatory microenvironment of the fracture gap, chondrogenesis, osteogenesis and osteoclastogenesis. We performed our analyses under conditions of reduced oxygen availability in order to mimic the in vivo situation of the fracture gap most optimal. We demonstrate that tofacitinib dose-dependently promotes the recruitment of hMSCs under hypoxia but inhibits recruitment of hMSCs under normoxia. With regard to the chondrogenic differentiation of hMSCs, we demonstrate that tofacitinib does not inhibit survival at therapeutically relevant doses of 10-100 nM. Moreover, tofacitinib dose-dependently enhances osteogenic differentiation of hMSCs and reduces osteoclast differentiation and activity. We conclude from our data that tofacitinib may influence bone healing by promotion of hMSC recruitment into the hypoxic microenvironment of the fracture gap but does not interfere with the cartilaginous phase of the soft callus phase of fracture healing process. We assume that tofacitinib may promote bone formation and reduce bone resorption, which could in part explain the positive impact of tofacitinib on bone erosions in RA. Thus, we hypothesize that it will be unnecessary to stop this medication in case of fracture and suggest that positive effects on osteoporosis are likely