Abstract Safety assessment relating to the presence of impurities, residual materials and contaminants in vaccines is a focus area of research at the United States Food and Drug Administration (FDA). Sponsors who submit Investigational New Drug (IND) applications for new vaccine products must report the results of safety assessments to the Division of Vaccines and Related Products Applications (DVRPA). Scientifically defining thresholds of toxicological concern (TTCs) as they apply to vaccine constituents will provide a useful aid to the sponsors and public regarding safety assessments of compounds for which there is little or no toxicity data. TTCs are mathematically modeled and extrapolated levels, below which adverse human health effects are not expected to occur (Kroes, 2004). In this project, we accessed DVRPA's submission databases and open source data to yield an initial chemical test set. Using INCHEM, RepDose, RTECS and TOXNET, we gathered LD50 and TDLo data. Using a structure-based decision tree, provided in the ToxTree software package, (3) different algorithms (The Cramer extended, the In vivo rodent micronucleus assay, and the Benigni-Bossa rule base for carcinogenicity by ISS) were applied to assign the initial test set (n= 197) of chemicals into structural families based on structural alerts (SAs). This resulted in six (6) potential methods for elucidating TTCs: In vivo rodent micronucleus assay/ LD50, Benigni-Bossa/ LD50, Cramer extended/ LD50, In vivo rodent micronucleus assay/ TDLo, Benigni-Bossa/ TDLo, and the Cramer extended/ TDLo. After each algorithm designated two structural families each, the distribution of TDLo's and LD50's for each structural family was subjected to a preliminary data analysis using JMP statistical software version 9. Based on an analysis of quantiles, skew, and kurtosis, it was concluded that the TDLo dataset was of poor quality and was dropped from further analysis, and that the In vivo rodent micronucleus assay algorithm failed to partition the initial test set in a meaningful way, so it too was culled from further consideration. This resulted in (2) remaining TTC methods for further consideration: Benigni-Bossa/ LD50 and the Cramer extended/ LD50. The remaining methods were subjected to internal validation based on Gene-Tox, CCRIS, CPDB, IARC, and EPA classaifications for genotoxic mutagenicity and carcinogenicity. Validation parameters were calculated for both methods and it was determined that the Benigni-Bossa/ LD50 method outperformed the Cramer extended/ LD50 method in terms of specificity (87.2 vs. 48.1%#37;), accuracy (65.2 vs. 52.94%#37;), positive predictivity (66.6 vs. 50%#37;), negative predictivity (64.8 vs. 56.5%#37;), ROC+ (2 vs. 1) and ROC- (1.84 vs. 1.3). These results indicated that the Benigni-Bossa/ LD50 was the most appropriate for calculating TTCs for vaccine constituents. For each class, the lower 2.5th percentile LD50 was extrapolated to a TTC value using safety estimates derived using uncertainty factors (UF) and adjusting for adult human weight. Final TTCs were designated as 18.06 μg/ person and 20.616 μg/ person for the Benigni-Bossa positive and negative structural families.

A common belief about inflation and economic growth has developed during recent years. This belief is that a “low” and stable inflation rate favors economic growth. The underlying arguments for this are that a low inflation rate create a beneficial playground for all participants. A playground which will meliorate investments and ensure a stability for consumers which in return will give a favorable environment for the economy to thrive. This paper aims to clarify this relationship between inflation and economic growth in Sweden between the period 1971-2017 and thus investigate the co-integration relation between the two variables. Additional test will be conducted to explore a potential threshold level of inflation. This threshold level is defined as the point where inflation starts to harm growth.

I Sverige finns det en brist på studier angående hydrologisk torka trots att det existerar problem med torka idag. Hydrologisk torka kan ha allvarliga konsekvenser på både naturen och samhället när det kommer till vattentillgång, växt -och djurliv och jordbruk. Av den anledningen är det viktigt att studier görs som undersöker allvarligheten i den hydrologiska torkan i Sverige för att få en bättre förståelse. I den här studien användes ett månadsvis Q95 värde som ett tröskelvärde med ett minimum av fem dagar i följd under tröskelvärdet för att definiera hydrologisk torka. Metoden applicerades på fem avrinningsområden in Sverige med data som sträckte sig mellan 1961- 2010. Resultatet från studien visade på att hydrologisk torka var speciellt framträdande under v issa år. Dessa år verkade vara kopplade till varandra under två till tre år i följd. De visade även ofta liknande månader och antal dagar under tröskelvärdet. Andra studier gjorda över de Nordiska länderna visade på liknande resultat. Metoden överensstämde även till en stor del av historisk torka i Sverige. För att kunna ge en större och komplett bild av hydrologisk torka diskuterades några möjliga metoder. Nederbörd, snö, strömflöde, evapotranspiration och grundvatten skulle behöva räknas med för en mer pr ecis studie. Standardiserade index kan täcka de mesta av de olika delarna, men för att få mera specifika förlustvärden så skulle även en tröskelnivå metod behöva implementeras i studien / In Sweden there is a lack of studies on the topic of hydrological drought even though it exist present problems of drought. Hydrological drought can have severe effects on both nature and society regarding water supply, animal life and agriculture. It is important to investigate the severity of hydrological drought in Sweden to get a better understanding of this phenomenon and its affects. To define hydrological drought this study used a Q95 monthly threshold with a minimum of 5 consecutive days below the threshold. This method was used on five catchments in Sweden with data ranging from 1961 -2010. The result from the study showed that hydrological drought was very prominent in some year s. These years seemed to be often linked together in two to three consecutive years. They often had similar amount of days and months below the threshold. Other studies over the Nordic countries showed similar results. The method also gave a result that to a certain degree showed droughts that coincided with historical records of drought in Sweden. This gave a positive feedback of the index accuracy. To get a broader picture of how hydrological drought propagates in Sweden some possible choices were discuss ed. Precipitation, snow, streamflow, evapotranspiration and groundwater would need to be covered for a more precise study. Standardized indices have most of spectrum covered, but it would be suggested to implement the threshold level method as well to get accurate deficits.

No description available.

Life and Institutions are some of the key factors of any culture. When it comes to successful communication with other cultures, Intercultural competence is crucial. The study of Life and Institutions should therefore by a mandatory part of teaching Czech as a foreign language. Based on extensive analysis, the thesis examines how Czech Life and Institutions are portrayed in select textbooks for foreigners reaching level B1 of the Common European Framework of Reference for Languages. The outcome of the thesis is not only a detailed charting of Life and Institutions found in textbooks of Czech language for foreigners, but also a set of major findings based on the initially proposed questions. The analysis of textbooks is based on theoretical findings, which are introduced in the first part of the thesis and which form the necessary framework for the research part of the thesis. Key words Intercultural competence, Life and Institutions, Culture, Textbooks of Czech language for Foreigners, Threshold level - Czech as a foreign language