Dissecting the molecular mechanisms of breast cancer bone metastasis for therapeutic targeting

Breast cancer that has metastasized to bone is currently an incurable disease, causing significant morbidity and mortality. The aim of this thesis work was to elucidate molecular mechanisms of bone metastasis and thereby gain insights into novel therapeutic approaches. First, we found that L‐serine biosynthesis genes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPH), were up‐regulated in highly bone metastatic MDA‐MB‐231(SA) cells as compared with the parental breast cancer cell line. Knockdown of serine biosynthesis inhibited proliferation of MDA‐MB‐231(SA) cells, and L‐serine was essential for the formation of bone resorbing osteoclasts. Clinical data demonstrated that high expression of PHGDH and PSAT1 was associated with decreased relapse‐free and overall survival and with features typical of poor outcome in breast cancer. Second, RNA interference screening pointed out heparan sulfate 6‐O‐sulfotransferase 2 (HS6ST2) as a critical gene for transforming growth factor β (TGF‐β)‐induced interleukin 11 (IL‐11) production in MDA‐MB‐231(SA) cells. Exogenous heparan sulfate glycosaminoglycans heparin and K5‐NSOS also inhibited TGF‐β‐induced IL‐11 production in MDA‐MB‐231(SA) cells. Furthermore, K5‐NSOS decreased osteolytic lesion area and tumor burden in bone in mice. Third, we discovered that the microRNAs miR‐204, ‐211 and ‐379 inhibited IL‐11 expression in MDA‐MB‐231(SA) cells through direct targeting of the IL‐11 mRNA. MiR‐379 also inhibited Smad‐mediated signaling. Gene expression profiling of miR‐204 and ‐379 transfected cells indicated that these microRNAs down‐regulate several bone metastasis‐relevant genes, including prostaglandin‐endoperoxide synthase 2 (PTGS2). Taken together, this study identified three potential treatment strategies for bone metastatic breast cancer: inhibition of serine biosynthesis, heparan sulfate glycosaminoglycans and restoration of miR‐204/‐211/‐379.

Treatment of Acute Otitis Media

Background: Acute otitis media (AOM) is the most common bacterial infection in young children, but the optimal management of AOM remains controversial. The aim of this study was to assess the efficacy of antimicrobial treatment, either immediate or delayed, for AOM and to compare parental experiences regarding the management of AOM in two countries with very different treatment guidelines. Methods: Altogether, 322 children participated in a randomized, double-blind, placebocontrolled trial. Children 6–35 months of age with AOM received amoxicillin-clavulanate or placebo for 7 days. The primary outcome was the time to treatment failure. In the second study, the delayed antimicrobial treatment group consisted of recipients of placebo who had received rescue treatment. The immediate antimicrobial treatment group consisted of children allocated to amoxicillin-clavulanate group. Parental expectations and opinions were evaluated by questionnaires sent via public day care in Turku, Finland, and Utrecht, the Netherlands. Results: Treatment failure occurred significantly more often in children receiving placebo as compared to antimicrobial treatment (45% vs. 19%, P<0.001). Delayed initiation of antimicrobial treatment did not worsen the recovery from AOM, but it was associated with worsening of the child’s condition, prolongation of symptoms, and absenteeism from day care and parental absenteeism from work. According to the comparative questionnaire, antimicrobial use was more common in Finland than in the Netherlands. Finnish parents believed more often than Dutch parents that antimicrobials are necessary in the treatment of AOM. Conclusions: Children with AOM benefit from antimicrobial treatment. Delayed initiation of antimicrobial does not worsen the overall recovery from AOM, but it might increase the symptom burden and create economic losses. Treatment practices and parental expectations seem to interact with each other. This needs to be considered when AOM treatment guidelines are updated.

Work-related crisis exposure : psychological trauma and PTSD in news journalists

I avhandlingen undersöktes hur journalister själva reagerar efter att ha arbetat med en plötslig krissituation, samt vilka faktorer som kan bidra till en förhöjd risk för allvarliga långsiktiga stressymptom. Temat undersöktes (1) genom att se på hur journalisters tidigare erfarenheter av krisuppdrag och traumatiska upplevelser i privatlivet var relaterade till stressymptom (posttraumatiskt stressyndrom, sekundär traumatisk stress, depression och utmattningssyndrom), och (2) genom att studera riskfaktorer i en identifierad typ av kris, de finländska skolskjutningarna 2007-08. Avhandlingens resultat baserades på enkätsvar från finländska nyhetsjournalister (N = 503) och intervjuer med personer som jobbat på plats vid skolskjutningar (N = 28). En klar majoritet av journalisterna hade inte allvarliga långsiktiga stressymptom vid tiden för undersökningen. De som varit på ett tidigare krisuppdrag där man bevittnat många obehagliga detaljer hade fler allvarliga stressymptom. En annan riskfaktor var att ha ett förflutet med fler traumatiska händelser i privatlivet. Bland de som arbetat med skolskjutningar var starka kortsiktiga reaktioner, t.ex. hjälplöshet och chock, relativt vanliga. Reaktionerna hörde ändå oftast till den normala återhämtningsprocessen, och ledde inte till en långsiktig försämring av måendet. Journalister som i hög grad identifierade sig med krisen, t.ex. personer med egna barn, hade större risk för att drabbas av allvarliga symptom på lång sikt. Detsamma gällde de som på plats upplevt journalistiska etiska dilemman, t.ex. att beordras av överordnade till uppdrag som gick emot egna principer. För att förebygga psykisk stress bland journalister är det viktigt att inom branschen sprida kunskap om stressreaktioner och utveckla rekommendationer för etisk krisjournalistik. Därmed kan journalister få bättre verktyg för att minimera risken att via sitt yrkesutövande orsaka ytterligare skada åt krisdrabbade.

Work for your happiness - Theoretical and empirical study defining and measuring happiness at work

There are vast changes in the work environment, and the traditional rules and management methods might not be suitable for today’s employees anymore. The meaning of work is also changing due to the younger and higher educated generations entering the markets. Old customs need to be re-validated and new approaches should be taken into use. This paper strongly emphasizes the importance of happiness research and happiness at work. The values towards the meaning of work are changing; people demand happiness and quality from all aspects of their lives. The aim of this study is to define happiness - especially at work - and to explain how it can be measured and what kind of results achieved. I also want to find out how the contents of work and the working environment might enhance happiness. The correlation between education and happiness is discussed and examined. I am aware that the findings and theories are concentrating mainly on Western Countries and highlighting the values and work-environments of those societies. The main aim of the empirical study is to find out if there are connections between happiness and work in data collected by World Value Survey in 2005, and if the profession has effects on happiness. Other factors such as the correlation of age, sex, education and income are examined too. I also want to find out what kind of values people have towards work and how these affect the happiness levels. The focus is on two nations: Finland (N=1014) and Italy (N=1012). I have also taken the global comparison within, that is all 54 countries (N=66,566) included in the 5th wave (during the years 2005 -2008) of the World Value Survey. The results suggest that people are generally happy around the world; happiness decreasing with the age, the educated being happier than the uneducated and the employed happier than the unemployed. People working in neat “white collar” jobs are more likely happier than those working in factories or outdoors. Money makes us happier, until certain level is reached. Work is important to people and the importance of work adds happiness. Work is also highly appreciated, but there are more happy people among those who do not appreciate work that highly. Safety matters the most when looking for a job, and there are more happy people among those who have selected the importance of work as the first choice when looking for a job, than among those to whom an income is the most important aspect. People are more likely happy when the quality of work is high, that is when their job consists of creative and cognitive tasks and when they have a feeling of independence.

Burden of Influenza in Children

Background: Most children with influenza are treated as outpatients but, especially among young children, influenza-attributable illnesses often result in hospitalization. However, relatively scarce data exist on the clinical picture and the full disease burden of pediatric influenza. Prompt diagnosis of influenza could enable the institution of antiviral therapy and adequate cohorting of patients. Data are needed to help clinicians correctly suspect influenza at the time of hospital admission. Aims and methods: We conducted a prospective 2-year cohort study of respiratory infections in children aged ≤13 years to determine the incidence of influenza in outpatient children and to assess the clinical presentation of influenza in various age groups seen in primary care. We also determined the rates of different complications attributable to influenza and the absenteeism of the children and their parents due to the child’s influenza infection. We then conducted a further 16-year retrospective study of children ≤16 years of age, hospitalized with virologically confirmed influenza. We estimated the population-based rates of hospitalizations and determined the primary admission diagnoses of the hospitalized children in different age groups. Results: The average annual rate of influenza was highest (179 / 1000) among children <3 years old. In this age group, acute otitis media was diagnosed as a complication of influenza in 40% of children. High fever was the most prominent sign of influenza, and 20% of children <3 years of age had a fever ≥40oC. Most children had rhinitis already during the first days of the illness. The average annual incidence of influenzarelated hospitalization was highest (276 / 100,000) among infants <6 months of age, of whom 52% were primarily admitted due to sepsis-like illnesses. Respiratory symptoms accounted for 38% of the hospitalizations. Conclusions: Influenza causes a substantial burden of illness on outpatient children and their families. The clinical presentation of influenza is most severe in children <3 years of age. The high incidence of influenza-associated hospitalizations among infants aged <6 months calls for more effective ways to prevent influenza in this age group. The clinical manifestations of influenza vary widely in different age groups of children at the time of hospital admission. Awareness of this phenomenon is important for the early recognition of the illness and the potential initiation of effective antiviral treatment of these patients.

We do the work you enjoy the trip

kuv., 10 x 21 cm

We do the work you enjoy the trip

kuv., 10 x 21 cm

Towards combining interactive mobile TV and smart spaces : architectures, tools and application development

Technological developments in microprocessors and ICT landscape have made a shift to a new era where computing power is embedded in numerous small distributed objects and devices in our everyday lives. These small computing devices are ne-tuned to perform a particular task and are increasingly reaching our society at every level. For example, home appliances such as programmable washing machines, microwave ovens etc., employ several sensors to improve performance and convenience. Similarly, cars have on-board computers that use information from many di erent sensors to control things such as fuel injectors, spark plug etc., to perform their tasks e ciently. These individual devices make life easy by helping in taking decisions and removing the burden from their users. All these objects and devices obtain some piece of information about the physical environment. Each of these devices is an island with no proper connectivity and information sharing between each other. Sharing of information between these heterogeneous devices could enable a whole new universe of innovative and intelligent applications. The information sharing between the devices is a diffcult task due to the heterogeneity and interoperability of devices. Smart Space vision is to overcome these issues of heterogeneity and interoperability so that the devices can understand each other and utilize services of each other by information sharing. This enables innovative local mashup applications based on shared data between heterogeneous devices. Smart homes are one such example of Smart Spaces which facilitate to bring the health care system to the patient, by intelligent interconnection of resources and their collective behavior, as opposed to bringing the patient into the health system. In addition, the use of mobile handheld devices has risen at a tremendous rate during the last few years and they have become an essential part of everyday life. Mobile phones o er a wide range of different services to their users including text and multimedia messages, Internet, audio, video, email applications and most recently TV services. The interactive TV provides a variety of applications for the viewers. The combination of interactive TV and the Smart Spaces could give innovative applications that are personalized, context-aware, ubiquitous and intelligent by enabling heterogeneous systems to collaborate each other by sharing information between them. There are many challenges in designing the frameworks and application development tools for rapid and easy development of these applications. The research work presented in this thesis addresses these issues. The original publications presented in the second part of this thesis propose architectures and methodologies for interactive and context-aware applications, and tools for the development of these applications. We demonstrated the suitability of our ontology-driven application development tools and rule basedapproach for the development of dynamic, context-aware ubiquitous iTV applications.

One chip solution for low-cost active magnetic bearing system

In this work the implementation of the active magnetic bearing control system in a single FPGA is studied. Requirements for the full magnetic bearing control system are reviewed. Different control methods for active magnetic bearings are described shortly. Flux and the current base controllers are implemented in a FPGA. Suitability of the con-trollers for a low-cost magnetic bearing application is studied. Floating-point arithmetic’s are used in the controllers to ease designing burden and improve calculation precision. Per-formance of the flux controller is verified with simulations.

Adult education policy in the European Union during the Lisbon decade : the shift to vocational adult learning and work skills matching

This doctoral dissertation investigates the adult education policy of the European Union (EU) in the framework of the Lisbon agenda 2000–2010, with a particular focus on the changes of policy orientation that occurred during this reference decade. The year 2006 can be considered, in fact, a turning point for the EU policy-making in the adult learning sector: a radical shift from a wide--ranging and comprehensive conception of educating adults towards a vocationally oriented understanding of this field and policy area has been observed, in particular in the second half of the so--called ‘Lisbon decade’. In this light, one of the principal objectives of the mainstream policy set by the Lisbon Strategy, that of fostering all forms of participation of adults in lifelong learning paths, appears to have muted its political background and vision in a very short period of time, reflecting an underlying polarisation and progressive transformation of European policy orientations. Hence, by means of content analysis and process tracing, it is shown that the new target of the EU adult education policy, in this framework, has shifted from citizens to workers, and the competence development model, borrowed from the corporate sector, has been established as the reference for the new policy road maps. This study draws on the theory of governance architectures and applies a post-ontological perspective to discuss whether the above trends are intrinsically due to the nature of the Lisbon Strategy, which encompasses education policies, and to what extent supranational actors and phenomena such as globalisation influence the European governance and decision--making. Moreover, it is shown that the way in which the EU is shaping the upgrading of skills and competences of adult learners is modeled around the needs of the ‘knowledge economy’, thus according a great deal of importance to the ‘new skills for new jobs’ and perhaps not enough to life skills in its broader sense which include, for example, social and civic competences: these are actually often promoted but rarely implemented in depth in the EU policy documents. In this framework, it is conveyed how different EU policy areas are intertwined and interrelated with global phenomena, and it is emphasised how far the building of the EU education systems should play a crucial role in the formation of critical thinking, civic competences and skills for a sustainable democratic citizenship, from which a truly cohesive and inclusive society fundamentally depend, and a model of environmental and cosmopolitan adult education is proposed in order to address the challenges of the new millennium. In conclusion, an appraisal of the EU’s public policy, along with some personal thoughts on how progress might be pursued and actualised, is outlined.

“Development work thesis” as a tool for continuing professional education

Julkaisumaa: 158 TW TWN Taiwan

m-Equine : IS support for the horse industry

The horse industry is in many ways still operating the same way as it did in the beginning of the 20th century. At the same time the role of the horse has changed dramatically, from a beast of burden to a top athlete, a production animal or a beloved pet. A racehorse or an equestrian sport horse is trained and taken care of like any other athlete, but unlike its human counterpart, it might end up on our plate. According to European and many other countries’ laws, a horse is a production animal. The medical data of a horse should be known if it is to be slaughtered, to ensure that the meat is safe for human consumption. Today this vital medical information should be noted in the horse’s passport, but this paperbased system is not reliable. If a horse gets sold, depending on the country’s laws, the medical records might not be transferred to the new owner, the horse’s passport might get lost etc. Thus the system is not fool proof. It is not only the horse owners who have to struggle with paperwork; veterinarians as well as other officials often use much time on redundant paperwork. The main research question of this thesis is if IS could be used to help the different stakeholders within the horse industry? Veterinarians in particular who travel to stables to treat horses cannot always take with them their computers, since the somewhat unsanitary environment is not suitable for a sensitive technological device. Currently there is no common medical database developed for horses, although such a database with a support system could help with many problems. These include vaccination and disease control, food-safety, as well as export and import problems. The main stakeholders within the horse industry, including equine veterinarians and horse owners, were studied to find out their daily routines and needs for a possible support system. The research showed that there are different aspects within the horse industry where IS could be used to support the stakeholders daily routines. Thus a support system including web and mobile accessibility for the main stakeholders is under development. Since veterinarians will be the main users of this support system, it is very important to make sure that they find it useful and beneficial in their daily work. To ensure a desired result, the research and development of the system has been done iteratively with the stakeholders following the Action Design Research methodology.

Scientific creativity and diversity of physical work environment: framework development

The aim of this research was to develop a framework to analyze how physical environment influences scientific creativity. Due to the relative novelty of this topic, there is still a gap in the unified method to study connection between physical environment and creativity. Therefore, in order to study this issue deeply, the qualitative method was used (interviews and qualitative questionnaire). Scientists (PhD students and senior researchers) of Graduate School of Management were interviewed to build the model and one expert interview was conducted to assess its validity. The model highlights several dimensions via which physical environment can influence scientific creativity: Comfort, Instruments and Diversity. Comfort and Instruments are considered to be related mostly to productivity, an initial requirement for creativity, while Diversity is the factor responsible for supporting all the stages of scientific creative process. Thus, creative physical environment is not one place by its nature, but an aggregative phenomenon. Due to two levels of analysis, the model is named the two-level model of creative physical environment.