Development and application of computational methodologies in qualitative modeling

La présente thèse s'intitule "Développent et Application des Méthodologies Computationnelles pour la Modélisation Qualitative". Elle comprend tous les différents projets que j'ai entrepris en tant que doctorante. Plutôt qu'une mise en oeuvre systématique d'un cadre défini a priori, cette thèse devrait être considérée comme une exploration des méthodes qui peuvent nous aider à déduire le plan de processus regulatoires et de signalisation. Cette exploration a été mue par des questions biologiques concrètes, plutôt que par des investigations théoriques. Bien que tous les projets aient inclus des systèmes divergents (réseaux régulateurs de gènes du cycle cellulaire, réseaux de signalisation de cellules pulmonaires) ainsi que des organismes (levure à fission, levure bourgeonnante, rat, humain), nos objectifs étaient complémentaires et cohérents. Le projet principal de la thèse est la modélisation du réseau de l'initiation de septation (SIN) du S.pombe. La cytokinèse dans la levure à fission est contrôlée par le SIN, un réseau signalant de protéines kinases qui utilise le corps à pôle-fuseau comme échafaudage. Afin de décrire le comportement qualitatif du système et prédire des comportements mutants inconnus, nous avons décidé d'adopter l'approche de la modélisation booléenne. Dans cette thèse, nous présentons la construction d'un modèle booléen étendu du SIN, comprenant la plupart des composantes et des régulateurs du SIN en tant que noeuds individuels et testable expérimentalement. Ce modèle utilise des niveaux d'activité du CDK comme noeuds de contrôle pour la simulation d'évènements du SIN à différents stades du cycle cellulaire. Ce modèle a été optimisé en utilisant des expériences d'un seul "knock-out" avec des effets phénotypiques connus comme set d'entraînement. Il a permis de prédire correctement un set d'évaluation de "knock-out" doubles. De plus, le modèle a fait des prédictions in silico qui ont été validées in vivo, permettant d'obtenir de nouvelles idées de la régulation et l'organisation hiérarchique du SIN. Un autre projet concernant le cycle cellulaire qui fait partie de cette thèse a été la construction d'un modèle qualitatif et minimal de la réciprocité des cyclines dans la S.cerevisiae. Les protéines Clb dans la levure bourgeonnante présentent une activation et une dégradation caractéristique et séquentielle durant le cycle cellulaire, qu'on appelle communément les vagues des Clbs. Cet évènement est coordonné avec la courbe d'activation inverse du Sic1, qui a un rôle inhibitoire dans le système. Pour l'identification des modèles qualitatifs minimaux qui peuvent expliquer ce phénomène, nous avons sélectionné des expériences bien définies et construit tous les modèles minimaux possibles qui, une fois simulés, reproduisent les résultats attendus. Les modèles ont été filtrés en utilisant des simulations ODE qualitatives et standardisées; seules celles qui reproduisaient le phénotype des vagues ont été gardées. L'ensemble des modèles minimaux peut être utilisé pour suggérer des relations regulatoires entre les molécules participant qui peuvent ensuite être testées expérimentalement. Enfin, durant mon doctorat, j'ai participé au SBV Improver Challenge. Le but était de déduire des réseaux spécifiques à des espèces (humain et rat) en utilisant des données de phosphoprotéines, d'expressions des gènes et des cytokines, ainsi qu'un réseau de référence, qui était mis à disposition comme donnée préalable. Notre solution pour ce concours a pris la troisième place. L'approche utilisée est expliquée en détail dans le dernier chapitre de la thèse. -- The present dissertation is entitled "Development and Application of Computational Methodologies in Qualitative Modeling". It encompasses the diverse projects that were undertaken during my time as a PhD student. Instead of a systematic implementation of a framework defined a priori, this thesis should be considered as an exploration of the methods that can help us infer the blueprint of regulatory and signaling processes. This exploration was driven by concrete biological questions, rather than theoretical investigation. Even though the projects involved divergent systems (gene regulatory networks of cell cycle, signaling networks in lung cells), as well as organisms (fission yeast, budding yeast, rat, human), our goals were complementary and coherent. The main project of the thesis is the modeling of the Septation Initiation Network (SIN) in S.pombe. Cytokinesis in fission yeast is controlled by the SIN, a protein kinase signaling network that uses the spindle pole body as scaffold. In order to describe the qualitative behavior of the system and predict unknown mutant behaviors we decided to adopt a Boolean modeling approach. In this thesis, we report the construction of an extended, Boolean model of the SIN, comprising most SIN components and regulators as individual, experimentally testable nodes. The model uses CDK activity levels as control nodes for the simulation of SIN related events in different stages of the cell cycle. The model was optimized using single knock-out experiments of known phenotypic effect as a training set, and was able to correctly predict a double knock-out test set. Moreover, the model has made in silico predictions that have been validated in vivo, providing new insights into the regulation and hierarchical organization of the SIN. Another cell cycle related project that is part of this thesis was to create a qualitative, minimal model of cyclin interplay in S.cerevisiae. CLB proteins in budding yeast present a characteristic, sequential activation and decay during the cell cycle, commonly referred to as Clb waves. This event is coordinated with the inverse activation curve of Sic1, which has an inhibitory role in the system. To generate minimal qualitative models that can explain this phenomenon, we selected well-defined experiments and constructed all possible minimal models that, when simulated, reproduce the expected results. The models were filtered using standardized qualitative ODE simulations; only the ones reproducing the wave-like phenotype were kept. The set of minimal models can be used to suggest regulatory relations among the participating molecules, which will subsequently be tested experimentally. Finally, during my PhD I participated in the SBV Improver Challenge. The goal was to infer species-specific (human and rat) networks, using phosphoprotein, gene expression and cytokine data and a reference network provided as prior knowledge. Our solution to the challenge was selected as in the final chapter of the thesis.

The REporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD) Statement: Methods for Arriving at Consensus and Developing Reporting Guidelines.

OBJECTIVE: Routinely collected health data, collected for administrative and clinical purposes, without specific a priori research questions, are increasingly used for observational, comparative effectiveness, health services research, and clinical trials. The rapid evolution and availability of routinely collected data for research has brought to light specific issues not addressed by existing reporting guidelines. The aim of the present project was to determine the priorities of stakeholders in order to guide the development of the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. METHODS: Two modified electronic Delphi surveys were sent to stakeholders. The first determined themes deemed important to include in the RECORD statement, and was analyzed using qualitative methods. The second determined quantitative prioritization of the themes based on categorization of manuscript headings. The surveys were followed by a meeting of RECORD working committee, and re-engagement with stakeholders via an online commentary period. RESULTS: The qualitative survey (76 responses of 123 surveys sent) generated 10 overarching themes and 13 themes derived from existing STROBE categories. Highest-rated overall items for inclusion were: Disease/exposure identification algorithms; Characteristics of the population included in databases; and Characteristics of the data. In the quantitative survey (71 responses of 135 sent), the importance assigned to each of the compiled themes varied depending on the manuscript section to which they were assigned. Following the working committee meeting, online ranking by stakeholders provided feedback and resulted in revision of the final checklist. CONCLUSIONS: The RECORD statement incorporated the suggestions provided by a large, diverse group of stakeholders to create a reporting checklist specific to observational research using routinely collected health data. Our findings point to unique aspects of studies conducted with routinely collected health data and the perceived need for better reporting of methodological issues.

Informing patients about limits to confidentiality: A qualitative study in prisons.

AIM: Confidentiality is important in healthcare practice, however, under certain circumstances, confidentiality is breached. In this paper, mental health professionals' (MHPs) practices related to informing imprisoned patients about confidentiality and its limits are presented. METHODS: Twenty-four MHPs working in Swiss prisons were interviewed. Data analysis involved qualitative thematic coding and was validated by discussing results with external experts and study participants. RESULTS: For expert evaluations and court-ordered therapies, participants informed patients that information revealed during these consultations is not bound by confidentiality rules. The practice of routinely informing patients about confidentiality and its limits became more complex in voluntary therapies, for which participants described four approaches and provided justifications in favour of or against their use. CONCLUSIONS: Further training and continued education are needed to improve physicians' ethical and legal knowledge about confidentiality disclosures. In order to promote ethical practices, it is important to understand and address existing motivations, attitudes and behaviours that impede appropriate patient information. Our study adds important new knowledge about the limits to confidentiality, particularly for providers working with vulnerable populations. Results from this study reflect typical ethical and practical dilemmas faced by and of interest to physicians working in forensic medicine and other related settings.

Kannattavuusraportoinnin laadun arviointi data warehouse ratkaisussa Case: Paperiteollisuuden myynnin ja asiakaspalvelun tietojärjestelmä

Tutkielman tavoitteena oli selvittää, onko tutkielman tilaajan toteuttaman kannattavuusraportoinnin laatu käyttäjien mielestä riittävä. Kannattavuusraportointi on toteutettu data warehouse tekniikalla. Tutkielman tavoitteina oli myös määrittää, mitä ohjelmiston laatu tarkoittaa ja miten sitä voidaan arvioida. Tutkimuksessa käytettiin kvalitatiivista tutkimusmenetelmää. Laadun arviointiin käytetty aineisto kerättiin haastattelemalla seitsemäätoista kannattavuusraportoinnin aktiivikäyttäjää. Tutkielmassa ohjelmiston laatu tarkoittaa sen kykyä täyttää tai ylittää käyttäjiensä kohtuulliset toiveet ja odotukset. Laatua arvioitiin standardin ISO/IEC 9126 määrittelemällä kuudella laatuominaisuudella, jotka kuvaavat minimaalisella päällekkäisyydellä ohjelmiston laadun. Lisäksi arvioinnissa hyödynnettiin varsinaiseen standardiin kuulumatonta informatiivista liitettä, joka tarkentaa ISO/IEC 9126 standardissa esitettyjä laadun ominaispiirteitä. Tutkimuksen tuloksena voidaan todeta, että käyttäjien mukaan kannattavuusraportointi on tarpeeksi laadukas, sillä se pystyy tarjoamaan helppokäyttöisiä, oikeanmuotoisia raportteja riittävän hyvällä vasteajalla käyttäjien tarpeisiin. Tehokkaasta hyödyntämisestä voidaan päätellä data warehousen rakentamisen onnistuneen. Tutkimuksessa nousi esiin myös runsaasti kehittämis- ja parannusideoita, jotka toimivat yhtenä kehitystyön apuvälineenä tulevaisuudessa.

A qualitative study of adolescents with medically unexplained symptoms and their parents. Part 1: Experiences and impact on daily life.

Medically unexplained symptoms (MUS) are common among adolescents and are frequently encountered in primary care. Our aim was to explore how these adolescents and their parents experience the condition and its impact on their daily lives and to provide recommendations for health professionals. Using a qualitative approach, six focus groups and two individual interviews were conducted. These involved a total of ten adolescents with different types of MUS and sixteen parents. The respondents were recruited in a university hospital in Switzerland. A thematic analysis was conducted according to the Grounded Theory. The analysis of the data highlighted four core themes: disbelief, being different, concealing symptoms, and priority to adolescent's health. Transcending these themes was a core issue regarding the discrepancy between the strategies that adolescents and their parents use to cope with the symptoms. Health professionals should be made aware of the emotional needs of these patients and their families.

Qualitative, quantitative and temporal study of cutting agents for cocaine and heroin over 9 years

Forensic laboratories mainly focus on the qualification and the quantitation of the illicit drug under analysis as both aspects are used for judiciary purposes. Therefore, information related to cutting agents (adulterants and diluents) detected in illicit drugs is limited in the forensic literature. This article discusses the type and frequency of adulterants and diluents detected in more than 6000 cocaine specimens and 3000 heroin specimens, confiscated in western Switzerland from 2006 to 2014. The results show a homogeneous and quite unchanging adulteration for heroin, while for cocaine it could be characterised as heterogeneous and relatively dynamic. Furthermore, the results indicate that dilution affects more cocaine than heroin. Therefore, the results provided by this study tend to reveal differences between the respective structures of production or distribution of cocaine and heroin. This research seeks to promote the systematic analysis of cutting agents by forensic laboratories. Collecting and processing data related to the presence of cutting agents in illicit drug specimens produces relevant information to understand and to compare the structure of illicit drug markets.

A qualitative study of adolescents with medically unexplained symptoms and their parents

Il est fréquent en médecine de premier recours de rencontrer des adolescents exprimant des symptômes somatiques pour lesquels aucune des investigations entreprises n'a permis de rendre compte d'une pathologie organique. De tels symptômes sont retrouvés dans la littérature sous la terminologie de symptômes médicalement inexpliqués (MUS) ou des troubles fonctionnels. Bien que la prévalence des adolescents souffrant de MUS est fréquente, les médecins éprouvent encore beaucoup de difficultés à prendre en charge et communiquer avec ces patients, principalement en raison d'une incompréhension de leurs besoins et préoccupations tant dans leur vie quotidienne que lors d'une consultation au cabinet. Le but de notre étude est de comprendre les expériences et vécus des adolescents avec des MUS ainsi que de leurs parents afin d'aider le praticien dans la compréhension de son patient dans sa globalité et ainsi d'améliorer sa prise en charge. Dans le premier article présenté, nous nous sommes intéressés à la vie quotidienne de ces adolescents en étudiant leurs relations avec leur famille et leur entourage ainsi que les répercussions sur leurs parcours scolaire et leurs activités extrascolaires. Dans le second article nous nous sommes penchés sur les relations qu'entretiennent ces adolescents et leurs parents avec le système de santé. Nous avons collecté des données qualitatives en moyennant des groupes focus incluant 16 adolescents atteints de troubles fonctionnels et leurs parents. L'analyse a permis de faire émerger les difficultés que ces jeunes et leurs familles vivent au quotidien et comment ils sont confrontés à la solitude dû principalement à l'incompréhension sociale. Les résultats mettent aussi en évidence l'insatisfaction de ces jeunes et de leurs parents par rapport à la prise en charge médical, notamment en raison d'un manque de communication. -- Medically unexplained symptoms (MUS) are common among adolescents and are frequently encountered in primary care. Our aim was to explore how these adolescents and their parents experience the condition and its impact on their daily lives and to provide recommendations for health professionals. Using a qualitative approach, six focus groups and two individual interviews were conducted. These involved a total of ten adolescents with different types of MUS and sixteen parents. The respondents were recruited in a university hospital in Switzerland. A thematic analysis was conducted according to the Grounded Theory. The analysis of the data highlighted four core themes: disbelief, being different, concealing symptoms, and priority to adolescent's health. Transcending these themes was a core issue regarding the discrepancy between the strategies that adolescents and their parents use to cope with the symptoms. Health professionals should be made aware of the emotional needs of these patients and their families.

PhD Students’ Research Group Networks: a Qualitative Approach

This article examines the networks within the research groups where Spanish PhD students are pursuing their doctorate. Capó et al. (2007) used quantitative data to predict PhD students’ publishing performance from their background, attitudes, supervisors’ performance and research group networks. Variables related to the research group network had a negligible explanatory power on student performance once the remaining variables had been accounted for. In this article, a qualitative follow up of the same students is carried out using extreme case sampling and indepth interviews. The qualitative research shows networking as important for students. Out of the 115 aspects that students mention in the interviews as relevant to publishing in the qualitative research, 92 have to do with their supervisors, their research group or their network as a whole. Similarly, out of the 50 hindrances mentioned, 20 have to do with the networks or relations. The most commonly mentioned network-related topics are research group members pushing PhD students to publish, meeting researchers outside the research group, existence of other PhD students in the group, help with the PhD from group members, supervisor’s interest in the thesis, the possibility of discussing with experts on the PhD’s topic and frequent contact with the supervisor and research group members. Some of these characteristics were not, however, measured in the conventional quantitative social network survey

A qualitative analysis of immigrant population health practices in the Girona Healthcare Region

The research we present here forms part of a two-phase project - one quantitative and the other qualitative - assessing the use of primary health care services. This paper presents the qualitative phase of said research, which is aimed at ascertaining the needs, beliefs, barriers to access and health practices of the immigrant population in comparison with the native population, as well as the perceptions of healthcare professionals. Moroccan and sub-Saharan were the immigrants to who the qualitative phase was specifically addressed. The aims of this paper are as follows: to analyse any possible implications of family organisation in the health practices of the immigrant population; to ascertain social practices relating to illness; to understand the significances of sexual and reproductive health practices; and to ascertain the ideas and perceptions of immigrants, local people and professionals regarding health and the health system. Methods: qualitative research based on discursive analysis. Data gathering techniques consisted of discussion groups with health system users and semi-structured individual interviews with healthcare professionals. The sample was taken from the Basic Healthcare Areas of Salt and Banyoles (belonging to the Girona Healthcare Region), the discussion groups being comprised of (a) 6 immigrant Moroccan women, (b) 7 immigrant sub-Saharan African women and (c) 6 immigrant and native population men (2 native men, 2 Moroccan men and 2 sub-Saharan men); and the semi-structured interviews being conducted with the following healthcare professionals: (a) 3 gynaecologists, (b) 3 nurses and 1 administrative staff. Results: use of the healthcare system is linked to the perception of not being well, knowledge of the healthcare system, length of time resident in Spain and interiorization of traditional Western medicine as a cure mechanism. The divergences found among the groups of immigrants, local people and healthcare professionals with regard to healthcare education, use of the healthcare service, sexual and reproductive healthcare and reticence with regard to being attended by healthcare personnel of the opposite sex demonstrate a need to work with the immigrant population as a heterogeneous group. Conclusions: the results we have obtained support the idea that feeling unwell is a psycho-social process, as it takes place within a specific socio-cultural situation and spans a range of beliefs, perceptions and ideas regarding symptomology and how to treat it

Intrapreneurial activity's appearance in corporation - A qualitative case study

Työn tavoitteena on ollut ollut selvittää sisäisen yrittäjyyden toimintaa ja muotoja suuren korporaation kontekstissa. Tutkimuskysymys on: miten sisäinen yrittäjyys ilmenee Kesko:ssa? Tutkimusmenetelmä on kvalitatiivinen ja aineisto kerättiin puolitstrukturoiduilla haastatteluilla. Haastateltavat koostuivat Kesko korporaation työntekijöistä. Tutkimustulokset paljastavat, että sisäinen yrittäjyys ilmenee Kesko:ssa monella eri tavalla. Työntekijät ovat korkeasti sitoutuneita ja motivoituneita. Johto tarjoaa haastavia työtehtäviä työntekijöille, ja tiimityöskentely on korkealla tasolla. Työntekijät myös verkoistuivat aktiivisesti. Joissakin tapauksissa sisäinen yrittäjyys ilmenee Kesko:ssa siten, että työntekijä on valmis ottamaan oman sivuprojektin parantaakseen koko organisaation suorituskykyä. Tämän tapainen toiminta on mahdollista vain korkean oma-aloitteisuuden kautta.

Data management as a part of performance management: Case study about production reporting development project

Because of the increased availability of different kind of business intelligence technologies and tools it can be easy to fall in illusion that new technologies will automatically solve the problems of data management and reporting of the company. The management is not only about management of technology but also the management of processes and people. This thesis is focusing more into traditional data management and performance management of production processes which both can be seen as a requirement for long lasting development. Also some of the operative BI solutions are considered in the ideal state of reporting system. The objectives of this study are to examine what requirements effective performance management of production processes have for data management and reporting of the company and to see how they are effecting on the efficiency of it. The research is executed as a theoretical literary research about the subjects and as a qualitative case study about reporting development project of Finnsugar Ltd. The case study is examined through theoretical frameworks and by the active participant observation. To get a better picture about the ideal state of reporting system simple investment calculations are performed. According to the results of the research, requirements for effective performance management of production processes are automation in the collection of data, integration of operative databases, usage of efficient data management technologies like ETL (Extract, Transform, Load) processes, data warehouse (DW) and Online Analytical Processing (OLAP) and efficient management of processes, data and roles.

Value co-creation in gaming the industry: A qualitative research on virtual discussion forums

This study discusses the procedures of value co-creation that persist in gaming industry. The purpose of this study was to identify the procedures that persist in current video gaming industry which answers the main research problem how value is co-created in video gaming industry followed by three sub questions: (i) What is value co-creation in gaming industry? (ii) Who participates in value co-creation in gaming industry? (iii) What are the procedures that are involved in value co-creation in gaming industry? The theoretical background of the study consists of literature relating to the theory of marketing i.e., notion of value, conventional understanding of value creation, value chain, co-creation approach, co-production approach. The research adopted qualitative research approach. As a platform of relationship researcher used web 2.0 tool interface. Data were collected from the social networks and netnography method was applied for analyzing them. Findings show that customer and company both co-create optimum level of value while they interact with each other and within the customers as well. However mostly the C2C interaction, discussions and dialogues threads that emerged around the main discussion facilitated to co-create value. In this manner, companies require exploiting and further motivating, developing and supporting the interactions between customers participating in value creation. Hierarchy of value co-creation processes is the result derived from the identified challenges of value co-creation approach and discussion forums data analysis. Overall three general sets and seven topics were found that explored the phenomenon of customer to customer (C2C) and business to customer (B2C) interaction/debating for value co-creation through user generated contents. These topics describe how gamer contributes and interacts in co-creating value along with companies. A methodical quest in current research literature acknowledged numerous evolving flows of value in this study. These are general management perspective, new product development and innovation, virtual customer environment, service science and service dominant logic. Overall the topics deliver various realistic and conceptual implications for using and handling gamers in social networks for augmenting customers’ value co-creation process.

Practical Data Curation and Management for Institutional Repositories

Workshop at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

An examination of factors influencing ERP key-user satisfaction: A qualitative case study

Several companies are trying to improve their operation efficiency by implementing an enterprise resource planning (ERP) system that makes it possible to control the resources of the company in real time. However, the success of the implementation project is not a foregone conclusion; a significant part of these projects end in a failure, one way or another. Therefore it is important to investigate ERP system implementation more closely in order to increase understanding about factors influencing ERP system success and to improve the probability of a successful ERP implementation project. Consequently, this study was initiated because a manufacturing case company wanted to review the success of their ERP implementation project. To be exact, the case company hoped to gain both information about the success of the project and insight for future implementation improvement. This study investigated ERP success specifically by examining factors that influence ERP key-user satisfaction. User satisfaction is one of the most commonly applied indicators of information system success. The research data was mainly collected by conducting theme interviews. The subjects of the interviews were six key-users of the newly implemented ERP system. The interviewees were closely involved in the implementation project. Furthermore, they act as representative users that utilize the new system in everyday business processes. The collected data was analyzed by thematizing. Both data collection and analysis were guided by a theoretical frame of reference. This frame was based on previous research on the subject. The results of the study aligned with the theoretical framework to large extent. The four principal factors influencing key-user satisfaction were change management, contractor service, key-user’s system knowledge and characteristics of the ERP product itself. One of the most significant contributions of the research is that it confirmed the existence of a connection between change management and ERP key-user satisfaction. Furthermore, it discovered two new sub-factors influencing contractor service related key-user satisfaction. In addition, the research findings indicated that in order to improve the current level of key-user satisfaction, the case company should pay special attention to system functionality improvement and enhancement of the key-users’ knowledge. During similar implementation projects in the future, it would be important to assure the success of change management and contractor service related processes.

Integration of marketing research data in new product development. Case study: Food industry company

The aim of this master’s thesis is to provide a real life example of how marketing research data is used by different functions in the NPD process. In order to achieve this goal, a case study in a company was implemented where gathering, analysis, distribution and synthesis of marketing research data in NPD were studied. The main research question was formulated as follows: How is marketing research data integrated and used by different company functions in the NPD process? The theory part of the master’s thesis was focused on the discussion of the marketing function role in NPD, use of marketing research particularly in the food industry, as well as issues related to the marketing/R&D interface during the NPD process. The empirical part of the master’s thesis was based on qualitative explanatory case study research. Individual in-depth interviews with company representatives, company documents and online research were used for data collection and analyzed through triangulation method. The empirical findings advocate that the most important marketing data sources at the concept generation stage of NPD are: global trends monitoring, retailing audit and consumers insights. These data sets are crucial for establishing the potential of the product on the market and defining the desired features for the new product to be developed. The findings also suggest the example of successful crossfunctional communication during the NPD process with formal and informal communication patterns. General managerial recommendations are given on the integration in NPD of a strategy, process, continuous improvement, and motivated cross-functional product development teams.