The Effects of Self-Reinforcing Mechanisms on Firm Performance

This study empirically investigates the influence of the market-bound (i.e., interaction and network effects) on the firm-bound (i.e., scale and learning effects) self-reinforcing mechanisms, and their combined effect on product and organizational performance. The findings from a sample of 257 manufacturing firms reveal that interaction effects have a positive effect on network effects. Network effects have a positive impact on the potential for firms to realize scale and learning effects, which in turn, is positively related to their actual realization of these effects. The actual realization of scale and learning effects has a positive effect on product performance, which in turn positively influences organizational performance. These effects are robust across industries and provide ample opportunities for future research.management;economics;increasing returns;self-reinforcing mechanisms

A Managerial Perspective on the Logic of Increasing Returns

The focus of this study is on the challenges faced by managers in effectively dealing with the new management logic of increasing returns as the information and knowledge intensity of their transformation processes rises. Dealing with these challenges is especially relevant for companies currently making the transition from capital and physical labor intensive transformation processes (old economy) to information and knowledge intensive transformation processes (new economy). For these companies, this study provides a definition of increasing returns, explains the sources of increasing returns and develops tools for monitoring the realization of increasing returns. These tools are applied at the Randstad Group, a leading temporary employment agency based in the Netherlands, currently making the transition from the old to the new economy. The study concludes with a discussion of the management implications of the new logic of increasing returns and suggestions for further research.management;economics;interaction effects;increasing returns;network effects

Increasing Returns and Firm Performance: An Empirical Study

Dit proefschrift gaat over increasing returns: positieve feedbackeffecten in markten en bedrijven. Positieve feedback betekent dat success leidt tot vermeerderd succes en falen tot vermeerderd falen. Er zijn twee marktgerelateerde increasing returns mechanismen, netwerkeffecten en sociale interactie-effecten, en twee bedrijfsgerelateerde increasing returns mechanismen, schaaleffecten en leereffecten. Empirisch onderzoek naar de relaties tussen deze mechanismen en naar de gevolgen van increasing returns voor bedrijfsprestatie is relatief schaars. Met dit proefschrift heeft de onderzoeker tot doel een bijdrage te leveren aan het opvullen van deze leemte. Om dit te bereiken wordt in dit proefschrift gebruik gemaakt van concepten uit de economie en uit de managementwetenschappen, bouwend op de industrial organization theory of the firm. Voor dit proefschrift zijn drie empirische studies uitgevoerd. In deze studies zijn nieuwe meetmethoden ontwikkeld en getest en is primaire en secondaire data verzameld en geanalyseerd. De resultaten laten zien dat de aanwezigheid van increasing returns in de markt invloed heeft op de prestaties van bedrijven, maar altijd via de realisatie van increasing retursn binnen deze bedrijven. Het blijkt dus dat in een incresing returns markt het management een belangrijke factor vormt die de bedrijfsprestatie bepaalt. Het is daarom voor managers belangrijk dat zij de mechanismen van increasing returns in hun markten en ondernemingen begrijpen zodat ze hun strategisch handelen hierop kunnen afstemmen. Hierdoor zijn managers in staat om de mogelijkheden die door increaErik den Hartigh (1971) graduated in business economics at the Erasmus University Rotterdam. After his graduation he worked as a research assistant and later as a parttime strategy consultant with TVA developments bv, a specialized consulting firm for business strategy and strategic transformation. Simultaneously, he worked as a parttime doctoral student at the Erasmus University Rotterdam. In May 2003 he joined the Delft University of Technology as an assistant professor in the field of strategy and innovation.This thesis is about increasing returns: positive feedback effects in markets and firms. Positive feedback means that success causes further success and failure causes further failure. There are two market-based mechanisms of increasing returns, network effects and social interaction effects, and two firm-based mechanisms of increasing returns, scale effects and learning effects. Empirical research into the relations between these mechanisms and into the consequences of increasing returns for firm performance is relatively scarce. The aim of the researcher with this thesis is to fill part of this gap. Concepts taken from economics and management sciences are used, building on the industrial organization theory of the firm. Three empirical studies were conducted for which new measurement models were constructed and tested and for which primary and secondary data was collected and analyzed. The results show that the presence of increasing returns in the market influences firm performance, but always through the realization of increasing returns in the firm. This means that in an increasing returns market, management is an important factor determining firm performance. It is therefore essential for managers to understand the mechanisms of increasing returns in their markets and firms and for them to be able to act strategically upon those mechanisms. This will enable managers to exploit business opportunities arising from increasing returns and to avoid pitfalls, which should result in better firm performance

A Managerial Perspective on the Logic of Increasing Returns

The focus of this study is on the challenges faced by managers in effectively dealing with the new management logic of increasing returns as the information and knowledge intensi

The Effects of Self-Reinforcing Mechanisms on Firm Performance

This study empirically investigates the influence of the market-bound (i.e., interaction and network effects) on the firm-bound (i.e., scale and learning effects) self-r

How to Determine the Increasing Returns Sensitivity of Your Industry?

Increasing returns means that self-reinforcing mechanisms are at work within firms and markets. These mechanisms come in four forms: scale effects, learning effects, network effects and social interaction effects. Some industries are more sensitive to increasing returns than others. It is important that managers are able to assess the increasing returns sensitivity of their industry. Therefore we have developed an analytical tool that allows managers to assess their industry’s sensitivity to increasing returns. Four case studies are used to illustrate this typology. The analytic tool shows that an industry has high increasing returns sensitivity if a combination of the following situations exists: 1) high fixed costs and low, or even zero, variable costs, indicating a high sensitivity to scale effects, 2) a high level of complexity of the business process and/or the products, indicating a high sensitivity to learning effects, 3) low product utility and high network utility, indicating a high sensitivity to network effects and finally, 4) a high degree of social involvement by customers and potential customers, indicating a high sensitivity to social interaction effects

Everolimus pharmacokinetics and its exposure-toxicity relationship in patients with thyroid cancer

Contains fulltext : 172498.pdf (publisher's version ) (Open Access)BACKGROUND: Everolimus is a mTOR inhibitor used for the treatment of different solid malignancies. Many patients treated with the registered fixed 10 mg dose once daily are in need of dose interruptions, reductions or treatment discontinuation due to severe adverse events. This study determined the correlation between systemic everolimus exposure and toxicity. Additionally, the effect of different covariates on everolimus pharmacokinetics (PK) was explored. METHODS: Forty-two patients with advanced thyroid carcinoma were treated with 10 mg everolimus once daily. Serial pharmacokinetic sampling was performed on days 1 and 15. Subsequently, a population PK model was developed using NONMEM to estimate individual PK values used for analysis of an exposure-toxicity relationship. Furthermore, this model was used to investigate the influence of patient characteristics and genetic polymorphisms in genes coding for enzymes relevant in everolimus PK. RESULTS: Patients who required a dose reduction (n = 18) due to toxicity at any time during treatment had significant higher everolimus exposures [mean AUC0-24 (SD) 600 (274) vs. 395 (129) microg h/L, P = 0.008] than patients without a dose reduction (n = 22). A significant association between everolimus exposure and stomatitis was found in the four-level ordered logistic regression analysis (P = 0.047). The presence of at least one TTT haplotype in the ABCB1 gene was associated with a 21 % decrease in everolimus exposure. CONCLUSION: The current study showed that dose reductions and everolimus-induced stomatitis were strongly associated with systemic everolimus drug exposure in patients with cancer. Our findings confirm observations from another study in patients with cancer and show us that everolimus is a good candidate for individualized dosing in patients with cancer. CLINICALTRIAL. GOV NUMBER: NCT01118065

Response: Limited sampling strategies for once daily tacrolimus exposure monitoring

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Population pharmacokinetics and pharmacogenetics of once daily tacrolimus formulation in stable liver transplant recipients

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Attachment of HeLa cells during early G1 phase

Both growth factor directed and integrin dependent signal transduction were shown to take place directly after completion of mitosis. The local activation of these signal transduction cascades was investigated in early G1 cells. Interestingly, various key signal transduction proteins were found in blebs at the cell membrane within 30 min after mitosis. These membrane blebs appeared in round, mitotic-like cells and disappeared rapidly during spreading of the cells in G1 phase. In addition to tyrosine-phosphorylated proteins, the blebs contained also phosphorylated FAK and phosphorylated MAP kinase. The formation of membrane blebs in round, mitotic cells before cell spreading is not specific for mitotic cells, because similar features were observed in trypsinized cells. Just before cell spreading also these cells exhibited membrane blebs containing active signal transduction proteins. Inhibition of signal transduction did not affect membrane bleb formation, suggesting that the membrane blebs were formed independent of signal transduction