Bronchoprovocation studies to define mechanisms in asthma and airway inflammation

Bronchial provocations with a variety of stimuli have been widely used over the past 70 years in both asthma research as well as in daily clinical praxis in order to aid the physician to establish the asthma diagnosis. In research, the bronchoprovocation model represents an excellent tool to better understand asthma pathophysiology, and to assess the effects of different interventions and new investigational therapies. Most of the currently approved asthma therapeutic options have shown efficacy in previous studies using the bronchoprovocation setting. In the current thesis, a range of bronchial provocations was performed prior to and after treatment with pharmacological interventions with different mode of actions. Responses were measured in the airways in the form of induced bronchoconstriction and airway inflammation (sputum cell counts), as well as in other matrices (skin, blood, urine). For the first time, it was shown that treatment with the combination of budesonide-formoterol (bud/form) in a single inhaler taken three to four times per week provided the same magnitude of protection against exercise-induced bronchoconstriction (EIB) as to regular treatment with a low dose of budesonide. Moreover, subjects who received monotherapy with the short acting β2 agonist (SABA) terbutaline had no protection against EIB over time. These results question the place of SABA monotherapy in asthma treatment even for subjects with mild asthma. It is recommended to replace SABA monotherapy with intermittent use of bud/form, which can also be an alternative option to regular treatment with low dose inhaled corticosteroids (ICS). Furthermore, using an allergen bronchoprovocation model, it was demonstrated that treatment with the second-generation anti-IgE monoclonal antibody QGE031 (ligelizumab) elicited an inhibition of the early allergic response (EAR) that was three times greater than what was achieved by the currently approved anti-IgE treatment with omalizumab. In addition, the data showed that there were important differences in the allergen response in the airways compared to the skin during QGE031 therapy; the highest dose of QGE031 consistently supressed allergen induced skin test responses that persisted six weeks after the last dose was given, while there was a variable effect on the airway response that did not last six weeks after the last dose. These results elucidate the complexity of the IgE pathway and the different kinetics and tissue responses to anti-IgE therapy. Finally, this thesis answered some important questions about the role of cysteinyl leukotrienes (CysLTs) and in particular leukotriene E4 (LTE4) in asthma. The data showed that treatment with the potent CysLT1 receptor antagonist montelukast completely abolished the bronchoconstriction elicited by LTE4 inhalation in subjects with mild asthma. Urine was collected during the LTE4 provocations for analysis of lipid mediator excretion, which led to the serendipitous discovery of increased urinary excretion of metabolites of prostaglandin (PG) D2, as well as other lipid mediators after LTE4 inhalation. These novel findings add a new dimension, namely that LTE4, in addition to a direct bronchoconstrictive action, can also activate both the mast cell as well as other cells to produce secondary responses that can amplify or modify its primary effect. Thus, this thesis demonstrates that carefully planned and conducted studies using bronchial provocations in combination with various pharmacological interventions, can elucidate important mechanisms in asthma pathogenesis and reveal potential new targets for treatmen

Text Extraction and Web Searching in a Non-Latin Language

Recent studies of queries submitted to Internet Search Engines have shown that non-English queries and unclassifiable queries have nearly tripled during the last decade. Most search engines were originally engineered for English. They do not take full account of inflectional semantics nor, for example, diacritics or the use of capitals which is a common feature in languages other than English. The literature concludes that searching using non-English and non-Latin based queries results in lower success and requires additional user effort to achieve acceptable precision. The primary aim of this research study is to develop an evaluation methodology for identifying the shortcomings and measuring the effectiveness of search engines with non-English queries. It also proposes a number of solutions for the existing situation. A Greek query log is analyzed considering the morphological features of the Greek language. Also a text extraction experiment revealed some problems related to the encoding and the morphological and grammatical differences among semantically equivalent Greek terms. A first stopword list for Greek based on a domain independent collection has been produced and its application in Web searching has been studied. The effect of lemmatization of query terms and the factors influencing text based image retrieval in Greek are also studied. Finally, an instructional strategy is presented for teaching non-English students how to effectively utilize search engines. The evaluation of the capabilities of the search engines showed that international and nationwide search engines ignore most of the linguistic idiosyncrasies of Greek and other complex European languages. There is a lack of freely available non-English resources to work with (test corpus, linguistic resources, etc). The research showed that the application of standard IR techniques, such as stopword removal, stemming, lemmatization and query expansion, in Greek Web searching increases precision. i

Preserving Cultural Heritage Using Open Source Collection Management Tools

Open source software (OSS) popularity is growing steadily and many OSS systems could be used to preserve cultural heritage objects. Such solutions give the opportunity to organizations to afford the development of a digital collection. This paper focuses on reviewing two OSS tools, CollectionSpace and the Open Video Digital Library Toolkit and discuss on how these could be used for organizing digital replicas of cultural objects. The features of the software are presented and some examples are given

Digitization and Preservation of City Landmarks Using Limited and Free Web Services

This paper presents a practical approach for digitizing city landmarks based on free and limited Web resources. The digital replicas are then placed on the Web using popular services, like Google earth, and are accessible to a huge user base. The method is easily applicable and quite valuable to organizations with limited funding

An inquiry-based learning approach to teaching information retrieval

The study of information retrieval (IR) has increased in interest and importance with the explosive growth of online information in recent years. Learning about IR within formal courses of study enables users of search engines to use them more knowledgeably and effectively, while providing the starting point for the explorations of new researchers into novel search technologies. Although IR can be taught in a traditional manner of formal classroom instruction with students being led through the details of the subject and expected to reproduce this in assessment, the nature of IR as a topic makes it an ideal subject for inquiry-based learning approaches to teaching. In an inquiry-based learning approach students are introduced to the principles of a subject and then encouraged to develop their understanding by solving structured or open problems. Working through solutions in subsequent class discussions enables students to appreciate the availability of alternative solutions as proposed by their classmates. Following this approach students not only learn the details of IR techniques, but significantly, naturally learn to apply them in solution of problems. In doing this they not only gain an appreciation of alternative solutions to a problem, but also how to assess their relative strengths and weaknesses. Developing confidence and skills in problem solving enables student assessment to be structured around solution of problems. Thus students can be assessed on the basis of their understanding and ability to apply techniques, rather simply their skill at reciting facts. This has the additional benefit of encouraging general problem solving skills which can be of benefit in other subjects. This approach to teaching IR was successfully implemented in an undergraduate module where students were assessed in a written examination exploring their knowledge and understanding of the principles of IR and their ability to apply them to solving problems, and a written assignment based on developing an individual research proposal

Issues of work-life balance among JASIST authors and editors

International audienceMany dedicated scientists reject the concept of maintaining a “work-life balance.”They argue that work is actually a huge part of life. In the mindset of these scientists, weekdays and weekends are equally appropriate for working on their research. While we all have encountered such people, we may wonder about how frequent this condition is in other scientists in our field. This brief communication probes the degree of work-life balance issues among JASIST authors and editors. We collected and examined the publication histories for all 1,533 of the 2,402 papers published in JASIST between 2001 and 2012. Although there is no rush to submit, revise, or accept papers, we found that 11% of these events happened during weekends and that this trend has been increasing since 2005. Our findings suggest that working during the weekend may be one of the ways that scientists find to cope with the highly demanding era of “publish or perish.” We hope that our findings will raise an awareness of the steady increases in work among scientists before it affects our work-life balance even more