Systematic review of population pharmacokinetic analyses of imatinib and relationships with treatment outcomes

Several population pharmacokinetic (PPK) analyses of the anticancer drug imatinib have been performed to investigate different patient populations and covariate effects. The present analysis offers a systematic qualitative and quantitative summary and comparison of those. Its primary objective was to provide useful information for evaluating the expectedness of imatinib plasma concentration measurements in the frame of therapeutic drug monitoring. The secondary objective was to review clinically important concentration-effect relationships to provide help in evaluating the potential suitability of plasma concentration values. Nine PPK models describing total imatinib plasma concentration were identified. Parameter estimates were standardized to common covariate values whenever possible. Predicted median exposure (Cmin) was derived by simulations and ranged between models from 555 to 1388 ng/mL (grand median: 870 ng/mL and interquartile "reference" range: 520-1390 ng/mL). Covariates of potential clinical importance (up to 30% change in pharmacokinetic predicted by at least 1 model) included body weight, albumin, α1 acid glycoprotein, and white blood cell count. Various other covariates were included but were statistically not significant or seemed clinically less important or physiologically controversial. Concentration-response relationships had more importance below the average reference range and concentration-toxicity relationships above. Therapeutic drug monitoring-guided dosage adjustment seems justified for imatinib, but a formal predictive therapeutic range remains difficult to propose in the absence of prospective target concentration intervention trials. To evaluate the expectedness of a drug concentration measurement in practice, this review allows comparison of the measurement either to the average reference range or to a specific range accounting for individual patient characteristics. For future research, external PPK model validation or meta-model development should be considered.

Three essays on internationalization and firm entrepreneurial behavior

PAPER 1: A THEORY ON THE EFFECTS OF INTERNATIONALIZATION ON FIRM ENTREPRENEURIAL BEHAVIOR AND GROWTH Abstract This article addresses the relationship. Past findings reveal that the direct effects of internationalization on performance are mixed and inconclusive. Our framework integrates firm entrepreneurial behavior as a mediating force of the troublesome Drawing on the tension between the entrepreneurship literature and the organizational inertia theory, we argue that internationalization is key to minimizing the stifling effects of inertia and in engendering entrepreneurial behavior towards growth. We suggest that firms that internationalize at a young age and enjoy an intense degree of internationalization tend to become more entrepreneurial than do late and weakly internationalized firms. As a consequence, early and intense internationalizers experience superior growth. Aware of the inherent endogeneity of our propositions, we also discuss how consistent estimates can be obtained when testing the model empirically. PAPER 2: DOES INTERNATIONALIZATION MATTER FOR GROWTH? THE CASE OF SWISS SOFTWARE FIRMS. Abstract This paper seeks to address the issue of whether early and intense internationalization leads to superior firm growth. We revisit the hypotheses of previous studies within the emerging research domain of international entrepreneurship. Empirical analyses on the performance implications of internationalization have so far been limited and inconsistent. Our paper intends to make two contributions to the international entrepreneurship literature. First, we bring additional empirical evidence as to the inconclusive firm performance endogeneity in our causal model, using a sample of 103 Swiss international small and medium-sized enterprises (SMEs). On one hand, we find that the degree of internationalization significantly increases perceived firm growth (i.e., relative firm performance in a market); however, age at internationalization was unrelated to perceived firm growth. On the other hand, we reproduced the causal path of a highly cited study that showed how age at internationalization was significantly and negatively associated with objective firm growth (i.e., sales). Interestingly, our results support the study similar setting (OLS regression with comparable control variables); however, the effect for age at internationalization reverses when we correct for endogeneity. PAPER 3: EFFECT OF INTERNATIONALIZATION ON FIRM ENTREPRENEURIAL ORIENTATION AND PERFORMANCE: THE CASE OF SWISS SOFTWARE FIRMS. Abstract How does internationalization influence a firm orientation (EO) and is this related to firm growth? This paper inquires into the performance theorizing, we test a process model in which EO plays a mediating role in accounting for the relationship between internationalization and growth. We position this paper on the tension zone between the entrepreneurship literature and the organizational inertia theory. We lay out the argument that internationalization is source of opportunities that drives a firm and thus mitigates inertial pressure. Using a sample of Swiss software small and medium-sized enterprises (SMEs), we found that degree of internationalization (but not age of internationalization) increases EO, which subsequently increased firm growth.

Leadership at the upper echelons : three essays

"IT'S THE ECONOMY STUPID", BUT CHARISMA MATTERS TOO: A DUAL PROCESS MODEL OF PRESIDENTIAL ELECTION OUTCOMES. ABSTRACT Because charisma is assumed to be an important determinant of effective leadership, the extent to which a presidential nominee is more charismatic than his opponent should be an important determinant of voter choices. We computed a composite measure of the rhetorical richness of acceptances speeches given by U.S. presidential candidates at their national party convention. We added this marker of charisma to Ray C. Fair's presidential vote-share equation (1978; 2009). We theorized that voters decide using psychological attribution (i.e., due to macroeconomics and incumbency) as well as inferential processes (i.e., due to leader charismatic behavior) when voting. Controlling for the macro-level variables and incumbency in the Fair model, our results indicated that difference between nominees' charisma is a significant determinant of electoral success, particularly in close elections. This extended model significantly improves the precision of the Fair model and correctly predicts 23 out of the last 24 U.S. presidential elections. Paper 2: IT CEO LEADERSHIP, CORPORATE SOCIAL AND FINANCIAL PERFORMANCE. ABSTRACT We investigated whether CEO leadership predicted corporate financial performance (CFP) and corporate social performance (CSP). Using longitudinal data on 258 CEOs from 117 firms across 19 countries and 10 industry sectors, we found that determinants of CEO leadership (i.e., implicit motives) significantly predicted both CFP and CSP. As expected, the most consistent positive predictor was Responsibility Disposition when interacting with n (need for) Power. n Achievement and n Affiliation were generally negatively related or unrelated to outcomes. CSP was positively related to accounting measures of CFP. Our findings suggest that executive leader characteristics have important consequences for corporate level outcomes. Paper 3. PUNISHING THE POWERFUL: ATTRIBUTIONS OF BLAME AND LEADERSHIP ABSTRACT We propose that individuals are more lenient in attributing blame to leaders than to nonleaders. We advance a motivational explanation building on the perspective of punishment and on system justification theory. We conducted two scenario experiments which supported our proposition. In study 1, wrongdoer leader status was negatively related to blame and the perceived seriousness of the wrongdoing. In study 2, controlling for the Big-Five personality factor and individual differences in moral evaluation (i.e., moral foundations), wrongdoer leader status was negatively related with desired severity of punishment, and fair punishments were perceived as more just for non-leaders than for leaders.

Corporate responsibility in the postnational constellation : a multiple-case study

In my thesis I present the findings of a multiple-case study on the CSR approach of three multinational companies, applying Basu and Palazzo's (2008) CSR-character as a process model of sensemaking, Suchman's (1995) framework on legitimation strategies, and Habermas (1996) concept of deliberative democracy. The theoretical framework is based on the assumption of a postnational constellation (Habermas, 2001) which sends multinational companies onto a process of sensemaking (Weick, 1995) with regards to their responsibilities in a globalizing world. The major reason is that mainstream CSR-concepts are based on the assumption of a liberal market economy embedded in a nation state that do not fit the changing conditions for legitimation of corporate behavior in a globalizing world. For the purpose of this study, I primarily looked at two research questions: (i) How can the CSR approach of a multinational corporation be systematized empirically? (ii) What is the impact of the changing conditions in the postnational constellation on the CSR approach of the studied multinational corporations? For the analysis, I adopted a holistic approach (Patton, 1980), combining elements of a deductive and inductive theory building methodology (Eisenhardt, 1989b; Eisenhardt & Graebner, 2007; Glaser & Strauss, 1967; Van de Ven, 1992) and rigorous qualitative data analysis. Primary data was collected through 90 semi-structured interviews in two rounds with executives and managers in three multinational companies and their respective stakeholders. Raw data originating from interview tapes, field notes, and contact sheets was processed, stored, and managed using the software program QSR NVIVO 7. In the analysis, I applied qualitative methods to strengthen the interpretative part as well as quantitative methods to identify dominating dimensions and patterns. I found three different coping behaviors that provide insights into the corporate mindset. The results suggest that multinational corporations increasingly turn towards relational approaches of CSR to achieve moral legitimacy in formalized dialogical exchanges with their stakeholders since legitimacy can no longer be derived only from a national framework. I also looked at the degree to which they have reacted to the postnational constellation by the assumption of former state duties and the underlying reasoning. The findings indicate that CSR approaches become increasingly comprehensive through integrating political strategies that reflect the growing (self-) perception of multinational companies as political actors. Based on the results, I developed a model which relates the different dimensions of corporate responsibility to the discussion on deliberative democracy, global governance and social innovation to provide guidance for multinational companies in a postnational world. With my thesis, I contribute to management research by (i) delivering a comprehensive critique of the mainstream CSR-literature and (ii) filling the gap of thorough qualitative research on CSR in a globalizing world using the CSR-character as an empirical device, and (iii) to organizational studies by further advancing a deliberative view of the firm proposed by Scherer and Palazzo (2008).

Connecting India: The rise of standards in service offshoring

This paper explores the role of international standards in the globalisation of the service economy. Various strands of economic analyses consider that core attributes of services affect their ability to be reliably delocalised, industrialised and standardised. In contrast, international political economy (IPE) approaches draw attention to power configurations supporting conflicting use of standards across industries and nations. The paper examines the case of the Indian service industry in business process outsourcing to probe these opposing views. Our findings suggest that standards matter in types of services conventionally identified as unlikely to be standardised, and that their use raise little conflict. An IPE perspective on service standardisation highlights, however, the importance of potential power issues likely to be included in more progressive forms of standardisation

Lenguajes de modelado de procesos para Servicios Web Semánticos : Caso de estudio BPEL4WS y WSMO

Estudi de les tecnologies Web Service Modeling Ontology (WSMO) i Business Process Execution Language For Web Services (BPEL4WS) i anàlisi de WSMO i de BPEL4WS documentant els punts clau de cada tecnologia, a continuació se'n realitzarà una comparativa entre les esmentades tecnologies, posant una especial atenció a WSMO

The Network Company in Catalonia : ICT, Productivity, Competitiveness, Salaries and Performance in Catalonia's Companies. Research report (synthesis document)

Resum en anglès del projecte de recerca L'empresa xarxa a Catalunya. TIC, productivitat, competitivitat, salaris i beneficis a l'empresa catalana té com a objectiu principal constatar que la consolidació d'un nou model estratègic, organitzatiu i d'activitat empresarial, vinculat amb la inversió i l'ús de les TIC (o empresa xarxa), modifica substancialment els patrons de comportament dels resultats empresarials, en especial la productivitat, la competitivitat, les retribucions dels treballadors i el benefici. La contrastació empírica de les hipòtesis de treball l'hem feta per mitjà de les dades d'una enquesta a una mostra representativa de 2.038 empreses catalanes. Amb la perspectiva de l'impacte de la inversió i l'ús de les TIC no s'aprecia una relació directa entre els processos d'innovació digital i els resultats de l'activitat de l'empresa catalana. En aquest sentit, hem hagut de segmentar el teixit productiu català per a buscar les organitzacions en què el procés de coinnovació tecnològica digital i organitzativa és més present i en què la intensitat de l'ús del coneixement és un recurs molt freqüent per a poder copsar impactes rellevants en els principals resultats empresarials. Això és així perquè l'economia catalana, avui, presenta una estructura productiva dual.

L'empresa xarxa a Catalunya : TIC, productivitat, competitivitat, salaris i rendiment a les empreses de Catalunya. Informe final de recerca (volum II)

El projecte de recerca L'empresa xarxa a Catalunya. TIC, productivitat, competitivitat, salaris i beneficis a l'empresa catalana té com a objectiu principal constatar que la consolidació d'un nou model estratègic, organitzatiu i d'activitat empresarial, vinculat amb la inversió i l'ús de les TIC (o empresa xarxa), modifica substancialment els patrons de comportament dels resultats empresarials, en especial la productivitat, la competitivitat, les retribucions dels treballadors i el benefici. La contrastació empírica de les hipòtesis de treball l'hem feta per mitjà de les dades d'una enquesta a una mostra representativa de 2.038 empreses catalanes. Amb la perspectiva de l'impacte de la inversió i l'ús de les TIC no s'aprecia una relació directa entre els processos d'innovació digital i els resultats de l'activitat de l'empresa catalana. En aquest sentit, hem hagut de segmentar el teixit productiu català per a buscar les organitzacions en què el procés de coinnovació tecnològica digital i organitzativa és més present i en què la intensitat de l'ús del coneixement és un recurs molt freqüent per a poder copsar impactes rellevants en els principals resultats empresarials. Això és així perquè l'economia catalana, avui, presenta una estructura productiva dual.

L'empresa xarxa a Catalunya : TIC, productivitat, competitivitat, salaris i rendiment a les empreses de Catalunya. Informe final de recerca (volum I)

El projecte de recerca L'empresa xarxa a Catalunya. TIC, productivitat, competitivitat, salaris i beneficis a l'empresa catalana té com a objectiu principal constatar que la consolidació d'un nou model estratègic, organitzatiu i d'activitat empresarial, vinculat amb la inversió i l'ús de les TIC (o empresa xarxa), modifica substancialment els patrons de comportament dels resultats empresarials, en especial la productivitat, la competitivitat, les retribucions dels treballadors i el benefici. La contrastació empírica de les hipòtesis de treball l'hem feta per mitjà de les dades d'una enquesta a una mostra representativa de 2.038 empreses catalanes. Amb la perspectiva de l'impacte de la inversió i l'ús de les TIC no s'aprecia una relació directa entre els processos d'innovació digital i els resultats de l'activitat de l'empresa catalana. En aquest sentit, hem hagut de segmentar el teixit productiu català per a buscar les organitzacions en què el procés de coinnovació tecnològica digital i organitzativa és més present i en què la intensitat de l'ús del coneixement és un recurs molt freqüent per a poder copsar impactes rellevants en els principals resultats empresarials. Això és així perquè l'economia catalana, avui, presenta una estructura productiva dual.

Use of niche models in invasive species risk assessments.

Risk maps summarizing landscape suitability of novel areas for invading species can be valuable tools for preventing species' invasions or controlling their spread, but methods employed for development of such maps remain variable and unstandardized. We discuss several considerations in development of such models, including types of distributional information that should be used, the nature of explanatory variables that should be incorporated, and caveats regarding model testing and evaluation. We highlight that, in the case of invasive species, such distributional predictions should aim to derive the best hypothesis of the potential distribution of the species by using (1) all distributional information available, including information from both the native range and other invaded regions; (2) predictors linked as directly as is feasible to the physiological requirements of the species; and (3) modelling procedures that carefully avoid overfitting to the training data. Finally, model testing and evaluation should focus on well-predicted presences, and less on efficient prediction of absences; a k-fold regional cross-validation test is discussed.

Standards and service offshoring in India: Moving beyond industry and institutional specificities

Résumé Cet article examine le rôle joué par les normes internationales techniques dans la mondialisation des activités de service. Différentes approches d'économie considèrent que les spécificités des activités de services sont un frein à leur délocalisation, à leur industrialisation et à leur normalisation. A l'opposé de ces approches centrées sur les spécificités des activités de services, les approches d'économie politique internationale mettent en avant l'existence de configurations conflictuelles de pouvoir à l'oeuvre dans l'internationalisation des activités de services et ce, au-delà des limites sectorielles et nationales. Cet article examine le cas du secteur des centres d'appels et, plus généralement, celui de la sous-traitance des services aux entreprises (BPO) en Inde. Nos résultats suggèrent que les normes techniques sont importantes dans le secteur étudié, alors même que ces types de services sont conventionnellement identifiés comme étant peu susceptibles d'être soumis à des normes. Une perspective d'économie politique sur la normalisation des activités de service souligne comment la problématique du pouvoir investit la normalisation technique d'une dimension plus progressive à travers les thématiques du "travailleur", du "consommateur", ou de "l'environnement". Abstract This paper explores the role of international standards in the much-debated globalisation of the service economy. Various strands of economic analyses consider that core attributes of services affect their ability to be reliably delocalised, industrialised, and standardised. In contrast, international political economy approaches draw attention to power configurations supporting conflicting use of standards across industries and nations. The paper examines the case of the rising Indian service industry in customer centres and business process outsourcing to probe these opposing views. Our findings suggest that standards matter in types of services that conventional economic analyses identify as unlikely to be standardised, and that the standards used in the Indian BPO industry are widely accepted. Despite little conflict in actual definitions of market requirements, an international political economy perspective on service standardisation highlights the importance of potential power issues related to workers', consumers', and environmental concerns likely to be included in more progressive forms of standardisation.

Intranetin ylläpitoprosessin kehittäminen

Työn tavoitteena on tutkia intranetin ylläpitoprosessien merkitystä sisäisen viestinnän, tiedonhallinnan ja käytettävyyden kannalta. Työn kirjallisuusosuuden tavoitteena on tutustua yrityksen sisäisen viestinnän eri tekijöihin, tavoitteisiin, merkityksiin ja menetelmiin. Intranetin roolia organisaation kontekstissa tarkastellaan näkökulmista: organisaatio, tieto organisaatiossa, organisaatioiden sisäinen viestintä ja viestintäteknologian keinot sisäiseen viestintään. Kirjallisuusosan toisena tavoitteena on tutustua käyttäjäkeskeisen suunnittelun lähtökohtiin ja malleihin. Nykypäivän tuotteissa käyttäjäkeskeisyys on itsestään selvää, ja se otetaankin huomioon jo tuotesuunnittelun alkuvaiheista lähtien. Työssä tutustutaan kolmeen käyttäjäkeskeisen suunnittelun prosessimalliin: ISO 13407 –prosessimalli, Usability engineering lifecycle ja vaatimusmäärittelyn spiraalimalli. Työssä esitellään myös käyttäjäkeskeisen vaatimusmäärittelyn toteuttamiseen liittyviä vaiheita, tekijöitä ja toimenpiteitä. Työn käytännönosuudessa tarkastellaan case-yrityksen intranet-palvelun nykytilannetta ja kuvataan nykyinen ylläpitoprosessi ja sen ongelmakohdat. Työn tavoitteena on pohtia ratkaisuja näihin ongelmiin. Käytännössä tämä tarkoittaa intranetin vaatimusmäärittelyn tekemistä, jonka pohjalta voidaan tunnistaa kehityskohteet ja tehdä suunnitelma toimintojen kehittämisestä. Työn lopputuloksena saadaan prosessien kuvaus, joilla ylläpito hoituu parhaiten.

Katalysaattorin valmistuksen benchmarking

Työn tarkoituksena oli selvittää kilpailullisen benchmarkingin avulla Ecocat Oy:n käyttämien katalysaattoreiden valmistusmenetelmien suhdetta kilpailijoiden käyttämiin valmistusmenetelmiin, sekä tehdä benchmarking-tiedon pohjalta johtopäätöksiä ja ehdotuksia valmistusmenetelmien kehittämisestä. Tutkimuksen runkonatoimi benchmarking-prosessimalli, joka oli yhdistelmä kolmesta työn teoriaosassa esitellystä benchmarking-prosessimallista. Tiedon keruu benchmarkingia varten tapahtui käyttämällä hyväksi julkisten lähteiden lisäksi yrityksen sisäisiä tietolähteitä ja yrityksen ulkopuolisia kontakteja. Kerätyn tiedon pohjalta laadittiin kuvaukset Ecocatin ja sen kilpailijoiden käyttämistä valmistusmenetelmistä, tuotteista ja kustannuksista. Laadittujen kuvausten pohjalta suoritettiin vertailua menetelmien, tuotteiden ja kustannusten kesken. Tutkimuksessa havaittiin että Ecocatin käyttämät valmistusmenetelmät ovat kilpailukykyisiäja hyvin samankaltaisia kuin kilpailijoilla. Valmistusmenetelmien kehitysehdotusten tekemiseen kilpailullinen benchmarking antoi niukasti tietoa. Menetelmien kehittämiseen soveltuisikin paremmin jokin toinen benchmarking-tekniikka ja avoimempi benchmarking-yhteistyö.

Tuotekehitys- ja innovaatioprosessin kehittäminen yrityksessä

Tutkimus käsittelee tuotekehitys- ja innovaatioprosessin kehittämistä ja sen vakiinnuttamista kohdeyrityksissä A ja B. Työssä luodaan ensin kirjallisuustutkimuksena yleinen teoreettinen viitekehys ja lähtötilannemalli tuotekehitys- ja innovaatioprosessin referenssimallille. Tämän vaiheen aikanakäsitellään erilaisia elementtejä ja vaiheita, joita tarvitaan kehitysprosessinkuvaamiseen ja sen kehittämiseen. Prosessimallissa ovat keskeisessä osassa päätöspisteet, joiden arviointikriteereitä ja -tekniikoita työssä käsitellään osana portfolion hallinnan eri mahdollisuuksia. Kehitettyä teoreettista mallia lähdetään implementoimaan työn toisessa osassa kohdeyrityksiin A ja B. Implementoinninyhteydessä käydään läpi sekä prosessikuvaus että siihen liittyvät päätöskriteerit. Tutkimuksen lopputuloksena on yrityksille tuotettu esitys innovaatioprosessista ja sen eri osa-alueista tarkemmalla tasolla sekä tutkimuksen puitteissa rakennettu portfoliotyökalu, jolla kehitysprojekteja voidaan hallinnoida niiden eri vaiheissa.

ERP- järjestelmän tukiprosessin nykytilan analyysi ja prosessin kehittäminen

Diplomityön tavoitteena oli tunnistaa kohdeyrityksessä kehitysmahdollisuuksia. Kehitysmahdollisuuksien etsiminen käyttäjätukiprosessin aloitettiin prosessin nykytilan analysoinnilla, jolla pyrittiin tunnistamaan prosessin ominaisuuksia sekä ongelma-alueita, joita korjaamalla prosessia voitiin tehostaa. Tutkimus on jaettu teoria ja empiria osaan.Teorian alussa käsitellään tietotekniikkapalveluiden organisointia, jotta ymmärretään toiminnanohjausjärjestelmien ja niihin liittyvien tukiprosessien merkitys yrityksissä. Tämän jälkeen perehdytään prosessijohtamiseen ja sen keinoihin liiketoimintaprosessien kehittämiseen. Tuloksena voidaan sanoa, että prosessien virtaviivaistaminen on nopea ja edullinen tapa tehostaa prosessin toimintaa ja päivittää vanha prosessi vastaamaan yrityksen nykyisiä tarpeita. Prosessien virtaviivaistamisella ei saada suuria kustannussäästöjä, vaan hyödyt liittyvät prosessin tehostumiseen. Virtaviivaistetusta prosessista on poistettu turhat toiminnot ja se on suunniteltu vastaamaan tarkoitustaan parhaalla mahdollisella tavalla. Näin prosessin virtaviivaistaminen lisää myös asiakkaan kokemaa arvoa.