Regulation of Osteoblast Differentiation and Gene Expression by Phosphodiesterases and Bioactive Peptides

Bone is a mineralized tissue that enables multiple mechanical and metabolic functions to be carried out in the skeleton. Bone contains distinct cell types: osteoblasts (bone-forming cells), osteocytes (mature osteoblast that embedded in mineralized bone matrix) and the osteoclasts (bone-resorbing cells). Remodelling of bone begins early in foetal life, and once the skeleton is fully formed in young adults, almost all of the metabolic activity is in this form. Bone is constantly destroyed or resorbed by osteoclasts and then replaced by osteoblasts. Many bone diseases, i.e. osteoporosis, also known as bone loss, typically reflect an imbalance in skeletal turnover. The cyclic adenosine monophosphate (cAMP) and the cyclic guanosine monophosphate (cGMP) are second messengers involved in a variety of cellular responses to such extracellular agents as hormones and neurotransmitters. In the hormonal regulation of bone metabolism, i.e. via parathyroid hormone (PTH), parathyroid hormone-related peptide (PTHrp) and prostaglandin E2 signal via cAMP. cAMP and cGMP are formed by adenylate and guanylate cyclases and are degraded by phosphodiesterases (PDEs). PDEs determine the amplitudes of cyclic nucleotide-mediated hormonal responses and modulate the duration of the signal. The activities of the PDEs are regulated by multiple inputs from other signalling systems and are crucial points of cross-talk between the pathways. Food-derived bioactive peptides are reported to express a variety of functions in vivo. The angiotensin-converting enzymes (ACEs) are involved in the regulation of the specific maturation or degradation of a number of mammalian bioactive peptides. The bioactive peptides offer also a nutriceutical and a nutrigenomic aspect to bone cell biology. The aim of this study was to investigate the influence of PDEs and bioactive peptides on the activation and the differentiation of human osteoblast cells. The profile of PDEs in human osteoblast-like cells and the effect of glucocorticoids on the function of cAMP PDEs, were investigated at the mRNA and enzyme levels. The effects of PDEs on bone formation and osteoblast gene expression were determined with chemical inhibitors and siRNAs (short interfering RNAs). The influence of bioactive peptides on osteoblast gene expression and proliferation was studied at the mRNA and cellular levels. This work provides information on how PDEs are involved in the function and the differentiation of osteoblasts. The findings illustrate that gene-specific silencing with an RNA interference (RNAi) method is useful in inhibiting, the gene expression of specific PDEs and further, PDE7 inhibition upregulates several osteogenic genes and increases bALP activity and mineralization in human mesenchymal stem cells-derived osteoblasts. PDEs appear to be involved in a mechanism by which glucocorticoids affect cAMP signaling. This may provide a potential route in the formation of glucocorticoid-induced bone loss, involving the down-regulation of cAMP-PDE. PDEs may play an important role in the regulation of osteoblastic differentiation. Isoleucine-proline-proline (IPP), a bioactive peptide, possesses the potential to increase osteoblast proliferation, differentiation and signalling.

Pelon ja toivon välissä : Pätkätyöläisen urakerronta

This study analyzes the forming of the occupational identity of the well-educated fixed-term employees. Fixed-term employment contracts amongst the well-educated labour force are exceptionally common in Finland as compared to other European countries. Two groups of modern fixed-term employees are distinguished. The first comprises well-educated women employed in the public sector whose fixed-term employment often consists of successive periods as temporary substitutes. The other group comprises well-educated, upper white-collar men aged over 40, whose fixed-term employment careers often consist of jobs of project nature or posts that are filled for a fixed period only. Method of the study For the empirical data I interviewed 35 persons (26 women and 9 men) in 33 interviews, one of which was conducted by e-mail and one was a group interview. All the interviews were electronically recorded and coded. All the interviewees have two things in common: fixed-term employment and formal high education. Thirteen (13) of them are researchers, four nurses, four midwives, four journalists, and ten project experts. I used the snowball method to get in touch the interviewees. The first interviewees were those who were recommended by the trade unions and by my personal acquaintances. These interviewees, in turn, recommended other potential interviewees. In addition, announcements on the internet pages of the trade unions were used to reach other interviewees. In analysing process I read the research material several times to find the turning points in the narrative the interviewees told. I also searched for the most meaningful stories told and the meaning the interviewees gave to these stories and to the whole narrative. In addition to that I paid attention to co-production of the narrative with the interviewees and analyzed the narrative as performance to be able to search for the preferred identities the interviewees perform. (Riesman 2001, 698-701). I do not pay much attention to the question of truth of a narrative in the sense of its correspondence with facts; rather I think a working life narrative has two tasks: On the one hand one has to tell the facts and on the other hand, he/she has to describe the meaning of these facts to herself/himself. To emphasize the double nature of the narrative about one’s working life I analyzed the empirical data both by categorizing it according to the cultural models of storytelling (heroic story, comedy, irony and tragedy) and by studying the themes most of the interviewees talked about. Ethics of the study I chose to use narrative within qualitative interviews on the grounds that in my opinion is more ethical and more empowering than the more traditional structured interview methods. During the research process I carefully followed the ethical rules of a qualitative research. The purpose of the interviews and the research was told to the interviewees by giving them a written description of the study. Oral permission to use the interview in this research was obtained from the interviewees. The names and places, which are mentioned in the study, are changed to conceal the actual identity of the interviewees. I shared the analysis with the interviewees by sending each of them the first analysis of their personal interview. This way I asked them to make sure that the identity was hidden well enough and hoped to give interviewees a chance to look at their narratives, to instigate new actions and sustain the present one (Smith 2001, 721). Also I hoped to enjoy a new possibility of joint authorship. Main results As a result of the study I introduce six models of telling a story. The four typical western cultural models that guide the telling are: heroic story, comedy, tragedy and satirical story (Hänninen 1999). In addition to these models I found two ways of telling a career filled with fixed-term employments that differ significantly from traditional career story telling. However, the story models in which the interviewees pour their experience locates the fixed term employers work career in an imagined life trajectory and reveals the meaning they give to it. I analyze the many sided heroic story that Liisa tells as an example of the strength of the fear of failing or losing the job the fixed term employee feels. By this structure it is also possible to show that success is felt to be entirely a matter of chance. Tragedy, the failure in one’s trial to get something, is a model I introduce with the help of Vilppu’s story. This narrative gets its meaning both from the sorrow of the failure in the past and the rise of something new the teller has found. Aino tells her story as a comedy. By introducing her narrative, I suggest that the purpose of the comedy, a stronger social consensus, gets deeper and darker shade by fixed-term employment: one who works as a fixed term employee has to take his/her place in his/her work community by him/herself without the support the community gives to those in permanent position. By studying the satiric model Rauno uses, I argue that using irony both turns the power structures to a carnival and builds free space to the teller of the story and to the listener. Irony also helps in building a consensus, mutual understanding, between the teller and the listener and it shows the distance the teller tells to exist between him and others. Irony, however, demands some kind of success in one’s occupational career but also at least a minor disappointment in the progress of it. Helmi tells her story merely as a detective story. By introducing Helmi’s narrative, I argue that this story model strengthens the trust in fairness of the society the teller and the listener share. The analysis also emphasizes the central position of identity work, which is caused by fixed-term employment. Most of the interviewees talked about getting along in working life. I introduced Sari’s narrative as an example of this. In both of these latter narratives one’s personal character and habits are lifted as permanent parts of the actual professional expertise, which in turn varies according to different situations. By introducing these models, I reveal that the fixed-term employees have different strategies to cope with their job situations and these strategies vary according to their personal motives and situations and the actual purpose of the interview. However, I argue that they feel the space between their hopes and fears narrow and unsecure. In the research report I also introduce pieces of the stories – themes – that the interviewees use to build these survival strategies. They use their personal curriculum vitae or portfolio, their position in work community and their work morals to build their professional identity. Professional identity is flexible and varies in time and place, but even then it offers a tool to fix one’s identity work into something. It offers a viewpoint to society and a tool to measure one’s position in surrounding social nets. As one result of the study I analyze the position the fixed-term employees share on the edge of their job communities. I summarize the hopes and fears the interviewees have concerning employers, trade unions, educational institutions and the whole society. In their opinion, the solidarity between people has been weakened by the short-sighted power of the economy. The impact the fixed-term employment has on one’s professional identity and social capital is a many-sided and versatile process. Fixed-term employment both strengthens and weakens the professional identity, social capital and the building of trust. Fixed-term employment also affects one’s day-to-day life by excluding her/him from the norm and by one’s difficulty in making long-term plans (Jokinen 2005). Regardless of the nature of the job contract, the workers themselves are experts in making the best of their sometimes less than satisfying work life and they also build their professional identity by using creatively their education, work experiences and interpersonal relations. However, a long career of short fixed-term employments may seriously change the perception of employee about his/her role. He/she may start concentrating only in coping in his/her unsatisfactory situation and leaves the active improvement of the lousy working conditions to other people. Keywords: narrative, fixed-tem employment, occupational identity, work, story model, social capital, career  

Designing a blended learning model for primary school language learning

In Finland, there is a desperate need for flexible, reliable and functional multi-e-learning settings for pupils aged 11-13. Southern Finland has several ongoing e-learning projects, but none that develop a multiple setting, with learning and teaching occurring between more than two schools. In 2006, internet connections were not broadband and data transfer was mainly audio data. Connections and technical problems occurred, which were an obstacle to multi-e-learning. Internet connections today enable web-based learning in major parts of
Lapland and by 2015, broadband will reach even the remotest villages up north. Therefore, it is important to research the possibilities of multi-e-learning and to build collaborative, learner-centred, versatile network models for primary school-aged pupils. The resulting model will facilitate distance learning to extend education to rural, sparsely populated areas, and it will give a model of using mobile devices in language portfolios. This will promote regional equality and prevent exclusion. Working with portfolios provides the opportunity to develop mobility from a pedagogical point of view. It is important to study the pros and cons of mobile devices in producing artefacts on portfolios in e-learning and language learning settings.
The current study represents a design-based research approach. The design research approach includes two important aspects concerning the current research: ‘a teacher as researcher’ aspect, which means there is the possibility to be strongly involved in developing processes and an obstacle-aspect, which means that problems while developing, are seen as a
promoter in evolving the designed model, as apposed to negative results.

Designing a blended learning model for primary school language learning

In Finland, there is a desperate need for flexible, reliable and functional multi-e-learning settings for pupils aged 11-13. Southern Finland has several ongoing e-learning projects, but none that develop a multiple setting, with learning and teaching occurring between more than two schools. In 2006, internet connections were not broadband and data transfer was mainly audio data. Connections and technical problems occurred, which were an obstacle to multi-e-learning. Internet connections today enable web-based learning in major parts of Lapland and by 2015, broadband will reach even the remotest villages up north. Therefore, it is important to research the possibilities of multi-e-learning and to build collaborative, learner-centred, versatile network models for primary school-aged pupils. The resulting model will facilitate distance learning to extend education to rural, sparsely populated areas, and it will give a model of using mobile devices in language portfolios. This will promote regional equality and prevent exclusion. Working with portfolios provides the opportunity to develop mobility from a pedagogical point of view. It is important to study the pros and cons of mobile devices in producing artefacts on portfolios in e-learning and language learning settings. The current study represents a design-based research approach. The design research approach includes two important aspects concerning the current research: ‘a teacher as researcher’ aspect, which means there is the possibility to be strongly involved in developing processes and an obstacle-aspect, which means that problems while developing, are seen as a promoter in evolving the designed model, as apposed to negative results.

Modeling and Forecasting Implied Volatility: Implications for Trading, Pricing, and Risk Management

Modeling and forecasting of implied volatility (IV) is important to both practitioners and academics, especially in trading, pricing, hedging, and risk management activities, all of which require an accurate volatility. However, it has become challenging since the 1987 stock market crash, as implied volatilities (IVs) recovered from stock index options present two patterns: volatility smirk(skew) and volatility term-structure, if the two are examined at the same time, presents a rich implied volatility surface (IVS). This implies that the assumptions behind the Black-Scholes (1973) model do not hold empirically, as asset prices are mostly influenced by many underlying risk factors. This thesis, consists of four essays, is modeling and forecasting implied volatility in the presence of options markets’ empirical regularities. The first essay is modeling the dynamics IVS, it extends the Dumas, Fleming and Whaley (DFW) (1998) framework; for instance, using moneyness in the implied forward price and OTM put-call options on the FTSE100 index, a nonlinear optimization is used to estimate different models and thereby produce rich, smooth IVSs. Here, the constant-volatility model fails to explain the variations in the rich IVS. Next, it is found that three factors can explain about 69-88% of the variance in the IVS. Of this, on average, 56% is explained by the level factor, 15% by the term-structure factor, and the additional 7% by the jump-fear factor. The second essay proposes a quantile regression model for modeling contemporaneous asymmetric return-volatility relationship, which is the generalization of Hibbert et al. (2008) model. The results show strong negative asymmetric return-volatility relationship at various quantiles of IV distributions, it is monotonically increasing when moving from the median quantile to the uppermost quantile (i.e., 95%); therefore, OLS underestimates this relationship at upper quantiles. Additionally, the asymmetric relationship is more pronounced with the smirk (skew) adjusted volatility index measure in comparison to the old volatility index measure. Nonetheless, the volatility indices are ranked in terms of asymmetric volatility as follows: VIX, VSTOXX, VDAX, and VXN. The third essay examines the information content of the new-VDAX volatility index to forecast daily Value-at-Risk (VaR) estimates and compares its VaR forecasts with the forecasts of the Filtered Historical Simulation and RiskMetrics. All daily VaR models are then backtested from 1992-2009 using unconditional, independence, conditional coverage, and quadratic-score tests. It is found that the VDAX subsumes almost all information required for the volatility of daily VaR forecasts for a portfolio of the DAX30 index; implied-VaR models outperform all other VaR models. The fourth essay models the risk factors driving the swaption IVs. It is found that three factors can explain 94-97% of the variation in each of the EUR, USD, and GBP swaption IVs. There are significant linkages across factors, and bi-directional causality is at work between the factors implied by EUR and USD swaption IVs. Furthermore, the factors implied by EUR and USD IVs respond to each others’ shocks; however, surprisingly, GBP does not affect them. Second, the string market model calibration results show it can efficiently reproduce (or forecast) the volatility surface for each of the swaptions markets.

Modelling and Forecasting Property Rents and Returns (summary section only)

Recently, focus of real estate investment has expanded from the building-specific level to the aggregate portfolio level. The portfolio perspective requires investment analysis for real estate which is comparable with that of other asset classes, such as stocks and bonds. Thus, despite its distinctive features, such as heterogeneity, high unit value, illiquidity and the use of valuations to measure performance, real estate should not be considered in isolation. This means that techniques which are widely used for other assets classes can also be applied to real estate. An important part of investment strategies which support decisions on multi-asset portfolios is identifying the fundamentals of movements in property rents and returns, and predicting them on the basis of these fundamentals. The main objective of this thesis is to find the key drivers and the best methods for modelling and forecasting property rents and returns in markets which have experienced structural changes. The Finnish property market, which is a small European market with structural changes and limited property data, is used as a case study. The findings in the thesis show that is it possible to use modern econometric tools for modelling and forecasting property markets. The thesis consists of an introduction part and four essays. Essays 1 and 3 model Helsinki office rents and returns, and assess the suitability of alternative techniques for forecasting these series. Simple time series techniques are able to account for structural changes in the way markets operate, and thus provide the best forecasting tool. Theory-based econometric models, in particular error correction models, which are constrained by long-run information, are better for explaining past movements in rents and returns than for predicting their future movements. Essay 2 proceeds by examining the key drivers of rent movements for several property types in a number of Finnish property markets. The essay shows that commercial rents in local markets can be modelled using national macroeconomic variables and a panel approach. Finally, Essay 4 investigates whether forecasting models can be improved by accounting for asymmetric responses of office returns to the business cycle. The essay finds that the forecast performance of time series models can be improved by introducing asymmetries, and the improvement is sufficient to justify the extra computational time and effort associated with the application of these techniques.

Essays on the Linkages Between Financial Markets, and Risk Asymmetries (summary section only)

During the last few decades there have been far going financial market deregulation, technical development, advances in information technology, and standardization of legislation between countries. As a result, one can expect that financial markets have grown more interlinked. The proper understanding of the cross-market linkages has implications for investment and risk management, diversification, asset pricing, and regulation. The purpose of this research is to assess the degree of price, return, and volatility linkages between both geographic markets and asset categories within one country, Finland. Another purpose is to analyze risk asymmetries, i.e., the tendency of equity risk to be higher after negative events than after positive events of equal magnitude. The analysis is conducted both with respect to total risk (volatility), and systematic risk (beta). The thesis consists of an introductory part and four essays. The first essay studies to which extent international stock prices comove. The degree of comovements is low, indicating benefits from international diversification. The second essay examines the degree to which the Finnish market is linked to the “world market”. The total risk is divided into two parts, one relating to world factors, and one relating to domestic factors. The impact of world factors has increased over time. After 1993, when foreign investors were allowed to freely invest in Finnish assets, the risk level has been higher than previously. This was also the case during the economic recession in the beginning of the 1990’s. The third essay focuses on the stock, bond, and money markets in Finland. According to a trading model, the degree of volatility linkages should be strong. However, the results contradict this. The linkages are surprisingly weak, even negative. The stock market is the most independent, while the money market is affected by events on the two other markets. The fourth essay concentrates on volatility and beta asymmetries. Contrary to many international studies there are only few cases of risk asymmetries. When they occur, they tend to be driven by the market-wide component rather than the portfolio specific element.

Angel Investing in Finland: An Analysis Based on Agency Theory and the Incomplete Contracting Theory

Wealthy individuals - business angels who invest a share of their net worth in entrepreneurial ventures - form an essential part of an informal venture capital market that can secure funding for entrepreneurial ventures. In Finland, business angels represent an untapped pool of capital that can contribute to fostering entrepreneurial development. In addition, business angels can bridge knowledge gaps in new business ventures by means of making their human capital available. This study has two objectives. The first is to gain an understanding of the characteristics and investment behaviour of Finnish business angels. The strongest focus here is on the due diligence procedures and their involvement post investment. The second objective is to assess whether agency theory and the incomplete contacting theory are useful theoretical lenses in the arena of business angels. To achieve the second objective, this study investigates i) how risk is mitigated in the investment process, ii) how uncertainty influences the comprehensiveness of due diligence as well as iii) how control is allocated post investment. Research hypotheses are derived from assumptions underlying agency theory and the incomplete contacting theory. The data for this study comprise interviews with 53 business angels. In terms of sample size this is the largest on Finnish business angels. The research hypotheses in this study are tested using regression analysis. This study suggests that the Finnish informal venture capital market appears to be comprised of a limited number of business angels whose style of investing much resembles their formal counterparts’. Much focus is placed on managing risks prior to making the investment by strong selectiveness and by a relatively comprehensive due diligence. The involvement is rarely on a day-to-day basis and many business angels seem to see board membership as a more suitable alternative than involvement in the operations of an entrepreneurial venture. The uncertainty involved does not seem to drive an increase in due diligence. On the contrary, it would appear that due diligence is more rigorous in safer later stage investments and when the business angels have considerable previous experience as investors. Finnish business angels’ involvement post investment is best explained by their degree of ownership in the entrepreneurial venture. It seems that when investors feel they are sufficiently rewarded, in terms of an adequate equity stake, they are willing to involve themselves actively in their investments. The lack of support for a relationship between increased uncertainty and the comprehensiveness of due diligence may partly be explained by an increasing trend towards portfolio diversification. This is triggered by a taxation system that favours investments through investment companies rather than direct investments. Many business angels appear to have substituted a specialization strategy that builds on reducing uncertainty for a diversification strategy that builds on reducing firm specific (idiosyncratic) risk by holding shares in ventures whose returns are not expected to exhibit a strong positive correlation.

Multiple Perspectives on Networks: Conceptual Development, Application and Integration in an Entrepreneurial Context

Multiple Perspectives on Networks: Conceptual Development, Application and Integration in an Entrepreneurial Context. The purpose of this thesis is to enhance cross-fertilization between three different approaches to network research. The business network approach may contribute in terms of how relationships are created, developed and how tie content changes within ties, not only between them. The social network approach adds to the discussion by offering concepts of structural change on a network level. The network approach in entrepreneurship contributes by emphasizing network content, governance and structure as a way of understanding and capturing networks. This is discussed in the conceptual articles, Articles 2 and 3. The ultimate purpose of this thesis is to develop a theoretical and empirical understanding of network development processes. This is fulfilled by presenting a theoretical framework, which offers multiple views on process as a developmental outcome. The framework implies that change ought to be captured both within and among relationships over time in the firm as well as in the network. Consequently, changes in structure and interaction taking place simultaneously need to be included when doing research on network development. The connection between micro and macro levels is also stressed. Therefore, the entrepreneur or firm level needs to be implemented together with the network level. The surrounding environment impacts firm and network development and vice versa and hence needs to be integrated. Further, it is necessary to view network development not only as a way forward but to include both progression and regression as inevitable parts of the process. Finally, both stability and change should be taken into account as part of network development. Empirical results in Article 1 show support for a positive impact of networks on SME internationalization. Article 4 compares networks of novice, serial and portfolio entrepreneurs but the empirical results show little support for differences in the networks by type of entrepreneur. The results demonstrate that network interaction and structure is not directly impacted by type of entrepreneur involved. It indicates instead that network structure and interaction is more impacted by the development phase of the firm. This in turn is in line with the theoretical implications, stating that the development of the network and the firm impacts each other, as they co-evolve.

Maximum Loss Calculation using Scenario Analysis, Heavy Tails and Implied Volatility Patterns

The objective of this paper is to improve option risk monitoring by examining the information content of implied volatility and by introducing the calculation of a single-sum expected risk exposure similar to the Value-at-Risk. The figure is calculated in two steps. First, there is a need to estimate the value of a portfolio of options for a number of different market scenarios, while the second step is to summarize the information content of the estimated scenarios into a single-sum risk measure. This involves the use of probability theory and return distributions, which confronts the user with the problems of non-normality in the return distribution of the underlying asset. Here the hyperbolic distribution is used to describe one alternative for dealing with heavy tails. Results indicate that the information content of implied volatility is useful when predicting future large returns in the underlying asset. Further, the hyperbolic distribution provides a good fit to historical returns enabling a more accurate definition of statistical intervals and extreme events.

The Influence of World Factors on Finnish Stock Market Volatility

This paper investigates to what extent the volatility of Finnish stock portfolios is transmitted through the "world volatility". We operationalize the volatility processes of Finnish leverage, industry, and size portfolio returns by asymmetric GARCH specifications according to Glosten et al. (1993). We use daily return data for January, 2, 1987 to December 30, 1998. We find that the world shock significantly enters the domestic models, and that the impact has increased over time. This applies also for the variance ratios, and the correlations to the world. The larger the firm, the larger is the world impact. The conditional variance is higher during recessions. The asymmetry parameter is surprisingly non-significant, and the leverage hypothesis cannot be verified. The return generating process of the domestic portfolio returns does usually not include the world information set, thus indicating that the returns are generated by a segmented conditional asset pricing model.

Volatility Smile Dynamics in Scenario Analysis

The objective of this paper is to suggest a method that accounts for the impact of the volatility smile dynamics when performing scenario analysis for a portfolio consisting of vanilla options. As the volatility smile is documented to change at least with the level of implied at-the-money volatility, a suitable model is here included in the calculation process of the simulated market scenarios. By constructing simple portfolios of index options and comparing the ex ante risk exposure measured using different pricing methods to realized market values, ex post, the improvements of the incorporation of the model are monitored. The analyzed examples in the study generate results that statistically support that the most accurate scenarios are those calculated using the model accounting for the dynamics of the smile. Thus, we show that the differences emanating from the volatility smile are apparent and should be accounted for and that the methodology presented herein is one suitable alternative for doing so.

The impact of stock option incentives on investment and firm value

This paper analyzes the relations among firm-level stock option portfolio incentives, investment, and firm value based on a sample of Finnish firms during the time period 1987 – 2000. Utilizing exact and complete information regarding stock option portfolio characteristics, we find some evidence that firm investment is increasing in the incentives to increase stock price (delta) and risk (vega). Furthermore, we find strong evidence of a positive relation between both incentive effects and firm value (Tobin’s Q). In contrast, when we allow for stock option incentives, investment, and firm value to be simultaneously determined, we find no evidence that investment is increasing in incentives. However, even after controlling for endogeneity, we find that both incentive effects arising from stock option compensation display a positive and significant effect on firm value. Finally, in contradiction to earlier findings, we observe that neither Tobin’s Q nor investment drives incentives.

Customer Energy in Relationships

All companies have a portfolio of customer relationships. From a managerial standpoint the value of these customer relationships is a key issue. The aim of the paper is to introduce a conceptual framework for customers’ energy towards a service provider. Customer energy is defined as the cognitive, affective and behavioural effort a customer puts into the purchase of an offering. It is based on two dimensions: life theme involvement and relationship commitment. Data from a survey study of 425 customers of an online gambling site was combined with data about their individual purchases and activity. Analysis showed that involvement and commitment influence both customer behaviour and attitudes. Customer involvement was found to be strongly related to overall spending within a consumption area, whereas relationship commitment is a better predictor of the amount of money spent at a particular company. Dividing the customers into four different involvement / commitment segments revealed differences in churn rates, word-of-mouth, brand attitude, switching propensity and the use of the service for socializing. The framework provides a tool for customer management by revealing differences in fundamental drivers of customer behaviour resulting in completely new customer portfolios. Knowledge of customer energy allows companies to manage their communication and offering development better and provides insight into the risk of losing a customer.

Trends in Pharmaceutical Product Development 2000-2010

Merkittävä osa alkuperäislääkevalmistajien tutkimus- ja tuotekehityskuluista näyttää olevan suunnattu olemassa olevien lääkkeiden kehittämiseen. Tämä voi oletettavasti johtaa kiinnostaviin formulaatiokehitysstrategioihin. Tutkimuksen tarkoituksena oli selvittää, voidaanko farmaseuttisen tuotekehityksen trendejä havaita myönnettyjen myyntilupien perusteella. Tutkimuksen mielenkiinnon kohteena olivat myös suurimpien lääkeyritysten käyttämät elinkaaren hallinnan keinot, joilla suojataan myyvimpiä tuotteita geneeriseltä kilpailulta ja varmistetaan markkinaosuus. Tutkimuksen painopiste oli kiinteissä oraalisissa lääkevalmisteissa. Laadullisten ja määrällisten menetelmien yhdistelmää käytettiin laajan näkökulman saamiseksi tutkittavaan aiheeseen. Suomalaisten myyntilupaviranomaisten haastatteluja käytettiin keräämään taustatietoa tutkimuksen määrällistä osaa varten. Määrällinen osa koostui myyntilupatietokannoista, jotka käsittivät kaikkien menettelyjen kautta Suomessa myönnetyt myyntiluvat, keskitetyn menettelyn kautta EU:ssa myönnetyt myyntiluvat ja maailman kymmenen suurinta lääkeyritystä USA:ssa. Tutkimustulosten perusteella rinnakkaislääkkeiden määrässä tapahtui merkittävä nousu Suomessa kaikkien menettelyjen kautta myönnetyissä myyntiluvissa ja EU:ssa keskitetyn menettelyn kautta myönnetyissä myyntiluvissa vuosina 2000-2010. Tämä muutos saattaa ainakin osaksi johtua lainsäädännöllisistä muutoksista, joilla luotiin kannustimia rinnakkaislääkkeiden käyttöön ja valmistukseen, kuten lääkevaihto ja viitehintajärjestelmä. USA:n tiedot osoittivat suurten lääkevalmistajien kiinnostuksen elinkaaren hallintaan: suurin osa maailman kymmenelle suurimmalle lääkeyritykselle myönnetyistä myyntiluvista vuosina 2005-2010 oli tähän tarkoitukseen. Elinkaaren hallinnan suhde uusiin lääkeaineisiin oli lähes 4:1. Kiinteä oraalinen lääkemuoto on kiistatta kaikista suosituin tapa annostella lääke, minkä vahvistivat sekä arvioijien haastattelut että myyntilupatiedot. Kiinteiden oraalisten rooli oli entistäkin korostuneempi rinnakkaislääkkeiden kohdalla. Kun innovatiivisuutta mitattiin epätyypillisten annosmuotojen määrällä, USA:n tiedot kiinteistä oraalisista lääkemuodoista osoittivat vahvaa innovatiivisuutta Suomen ja EU:n tietoihin verrattuna. Tämä saattaa heijastaa suurten lääkeyritysten innovatiivista tuotevalikoimaa. Epätyypillisten kiinteiden oraalisten annosmuotojen osuus oli huomattavasti pienempi rinnakkaislääkkeissä kuin alkuperäislääkkeissä kaikilla alueilla. Elinkaaren hallinnassa käytetyimmät strategiat olivat uusi formulaatio, uusi vahvuus ja uusi yhdistelmä olemassa olevasta valmisteesta. Kiinteiden oraalisten lääkemuotojen osalta kaksi kolmasosaa uusista elinkaaren hallinnan formulaatioista oli säädellysti vapauttavia valmisteita. Elinkaaren hallinta on olennainen osa suurten lääkeyritysten liiketoimintastrategiaa, ja sen tärkeyttä havainnollistettiin Coreg-tablettien tapausesimerkillä.