Productivity shocks and aggregate fluctuations in an estimated endogenous growth model with human capital

Employing an endogenous growth model with human capital, this paper explores how productivity shocks in the goods and human capital producing sectors contribute to explaining aggregate fluctuations in output, consumption, investment and hours. Given the importance of accounting for both the dynamics and the trends in the data not captured by the theoretical growth model, we introduce a vector error correction model (VECM) of the measurement errors and estimate the model’s posterior density function using Bayesian methods. To contextualize our findings with those in the literature, we also assess whether the endogenous growth model or the standard real business cycle model better explains the observed variation in these aggregates. In addressing these issues we contribute to both the methods of analysis and the ongoing debate regarding the effects of innovations to productivity on macroeconomic activity.

Trade Costs, International Competition and Selection: The Effects of Unionisation on Market Size

Within a two-country model of international trade in which heterogeneous firms face firm-specific unions, we study the effects of different forms of trade liberalisation on market structure and competitive selection in the presence of inter-country asymmetries in size and labour market institutions. For given levels of trade openness, an increase in a country’s relative unions’ strength reduces the average productivity of its domestic producers but increases that of its exporters. Whilst an unfavourable union power differential, by increasing wages, weakens a country’s firms’ competitive position, the higher wages reinforce standard market access mechanisms to give rise to aggregate income effects. When the initial levels of trade openness are sufficiently low, this ‘expansionary’ aggregate effect can attract industry in the country with stronger unions and also result in an increase in the extensive margin of exports. For sufficiently large inter-country differences in the bargaining power of unions, trade liberalization can then result in a pro-variety effect, with an increase in the total availability of varieties to consumers in both countries, regardless of there being inter-country differences in size.

The Spillover Effects of Monitoring: A Field Experiment.

We provide field experimental evidence of the effects of monitoring in a context where productivity is multi-dimensional and only one dimension is monitored and incentivised. We hire students to do a job for us. The job consists of identifying euro coins. We study the effects of monitoring and penalising mistakes on work quality, and evaluate spillovers on non- incentivised dimensions of productivity (punctuality and theft). We .nd that monitoring improves work quality only if incentives are large, but reduces punctuality substantially irrespectively of the size of incentives. Monitoring does not affect theft, with ten per cent of participants stealing overall. Our setting also allows us to disentangle between possible theoretical mechanisms driving the adverse effects of monitoring. Our .ndings are supportive of a reciprocity mechanism, whereby workers retaliate for being distrusted.

Human capital spillovers, productivity and regional convergence in Spain

This paper analyses the differential impact of human capital, in terms of different levels of schooling, on regional productivity and convergence. The potential existence of geographical spillovers of human capital is also considered by applying spatial panel data techniques. The empirical analysis of Spanish provinces between 1980 and 2007 confirms the positive impact of human capital on regional productivity and convergence, but reveals no evidence of any positive geographical spillovers of human capital. In fact, in some specifications the spatial lag presented by tertiary studies has a negative effect on the variables under consideration.

Innovation sources and productivity in Catalonian firms: a quantile regression analysis

This paper explores the effects of two main sources of innovation - intramural and external R&D— on the productivity level in a sample of 3,267 Catalonian firms. The data set used is based on the official innovation survey of Catalonia which was a part of the Spanish sample of CIS4, covering the years 2002-2004. We compare empirical results by applying usual OLS and quantile regression techniques both in manufacturing and services industries. In quantile regression, results suggest different patterns at both innovation sources as we move across conditional quantiles. The elasticity of intramural R&D activities on productivity decreased when we move up the high productivity levels both in manufacturing and services sectors, while the effects of external R&D rise in high-technology industries but are more ambiguous in low-technology and knowledge-intensive services. JEL codes: O300, C100, O140 Keywords: Innovation sources, R&D, Productivity, Quantile Regression

Effects of unilateral motor cortex lesion on ipsilesional hand's reach and grasp performance in monkeys: relationship with recovery in the contralesional hand.

Manual dexterity, a prerogative of primates, is under the control of the corticospinal (CS) tract. Because 90-95% of CS axons decussate, it is assumed that this control is exerted essentially on the contralateral hand. Consistently, unilateral lesion of the hand representation in the motor cortex is followed by a complete loss of dexterity of the contralesional hand. During the months following lesion, spontaneous recovery of manual dexterity takes place to a highly variable extent across subjects, although largely incomplete. In the present study, we tested the hypothesis that after a significant postlesion period, manual performance in the ipsilesional hand is correlated with the extent of functional recovery in the contralesional hand. To this aim, ten adult macaque monkeys were subjected to permanent unilateral motor cortex lesion. Monkeys' manual performance was assessed for each hand during several months postlesion, using our standard behavioral test (modified Brinkman board task) that provides a quantitative measure of reach and grasp ability. The ipsilesional hand's performance was found to be significantly enhanced over the long term (100-300 days postlesion) in six of ten monkeys, with the six exhibiting the best, though incomplete, recovery of the contralesional hand. There was a statistically significant correlation (r = 0.932; P < 0.001) between performance in the ipsilesional hand after significant postlesion period and the extent of recovery of the contralesional hand. This observation is interpreted in terms of different possible mechanisms of recovery, dependent on the recruitment of motor areas in the lesioned and/or intact hemispheres.

Multinationals, R&D and productivity: Evidence for UK Manufactoring firms

In this study we analyze multinationality (domestic-based firms vs. multinationals) and foreignness (foreign vs. domestic firms) effects in the returns of R&D to productivity. We follow a two-step strategy. In the first step, we consistently ''s productivity by GMM and numerically compute the sample distribution of the R&D returns. In the second step, we use stochastic dominance techniques to make inferences on the multinationality and foreignness effects. Results for a panel of UK manufacturing firms suggest that multinationality and foreignness effects operate in an opposite way: whilst the multinationality effect enhances R&D returns, the foreignness diminishes them.

Characterization of the effects of IL-17F on CHO cell line generation

CHO is the most commonly used mammalian host for the generation of cell lines allowing for the production of high quality therapeutic proteins. The generation of such cell lines is a lengthy and resource-intensive process requiring extensive screening in order to isolate candidates with optimal characteristics, such as growth, stability and productivity. For this reason, the biotechnology industry invests much effort in attempts to optimize CHO expression systems in order to streamline and shorten the cell line selection process. Based on preliminary observations of a facilitated selection of CHO-GS cell lines expressing members of the IL-17 cytokine family, this study investigates the use of IL-17F as a novel enhancing factor for CHO cell line generation. Using two different CHO expression systems (exploiting GS and DHFR-based selection), we demonstrated that IL-17F expression caused a significant increase in the occurrence of colonies during the selection process. All colonies selected produced substantial amounts of IL-17F, suggesting that benefits were conferred, during selection, to those cells expressing the cytokine. Furthermore, transgene expression levels were significantly increased when the selection pressure was raised to a level that would not normally be permissive for colony selection (i.e. 100 |o.M MSX for the CHO-GS expression system or 1000 nM MTX for the CHO-DHFR system). Finally, IL-17F expression was also found to enhance the rate of appearance of clones during single cell subcloning in the absence of selection pressure. Overall, these benefits have the potential to allow a substantial reduction in the length of cell line generation while significantly increasing cell line productivity. Nevertheless, we found that the high IL-17F expression levels required to convey enhancing effects was a limitation when attempting to co-express IL-17F and a recombinant soluble protein of therapeutic interest from independent CMV promoters within the same expression vector. In order to understand and overcome this limitation, studies were designed to characterize the IL-17F enhancing effect at the molecular and cellular level. Regular supplementation of recombinant biologically-active IL-17F into the culture medium during cell line selection was not able to reproduce the enhancing effects of endogenous IL-17F expression. In addition, increased IL-17F expression correlated with increased CHO-GS selection transgene expression at the single cell level. This data suggested a possible effect of IL-17F on viral promoter activity or transgene mRNA stability. It also provided direct evidence that the cells expressing the highest amounts of IL-17F obtained the most benefit. Overall data obtained from these study implied that IL-17F may act through an intracellular mechanism, possibly exerted during secretion. We therefore initiated experiments designed to determine the specific compartment(s) within which IL-17F triggers its effect. This work has identified IL-17F as a potentially powerful tool to optimize the CHO cell line generation process. The characterization of this enhancing effect at the molecular level has given us several insights into overcoming the current limitations, thus paving the way for the development of a viable technology that can be exploited within the biotechnology industry. - La CHO est la cellule hôte de mammifere la plus couramment utilisée dans la création de lignée cellulaire produisant des protéines thérapeutiques de haute qualité. La génération de ces lignées cellulaires est un processus long et exigeant l'utilisation de techniques de sélection robustes afin d'isoler des candidats possédants les caractéristiques optimales de croissance, de productivité et de stabilité d'expression. Les industries biopharmaceutiques ont investi beaucoup d'efforts afin d'optimiser les systèmes d'expression CHO dans le but raccourcir la longueur du procédé de sélection de lignées cellulaires et aussi d'en augmenter l'efficacité. A partir d'observations préliminaires obtenues lors de la génération de lignées cellulaires CHO- GS exprimant une cytokine appartenant à la famille des IL-17, nous avons réalisé une étude portant sur l'utilisation de l'IL-17F humaine (IL-17F) comme nouveau facteur d'optimisation pour la génération de lignées cellulaires CHO. Nous avons démontré, en utilisant les deux systèmes de sélection et d'expression CHO couramment utilisés (le premier exploitant la GS et l'autre basée sur la DHFR), que l'expression de l'IL-17F permet une augmentation significative de la fréquence d'apparition de colonies durant le processus de sélection de lignées cellulaires. Les différentes colonies sélectionnées expriment des quantités substantielles d'IL-17F, suggérant un effet bénéfique lors de la sélection qui serait exclusivement conféré aux cellules exprimant la cytokine. En outre, le niveau d'expression du transgene se trouve significativement augmenté lorsque la pression de sélection est portée à un niveau habituellement trop élevé pour permettre la sélection de colonies (soit 100 |JM MSX pour le système d'expression CHO-GS ou 1000 nM MTX pour le système CHO- DHFR). Enfin, l'expression d'IL-17F permet également d'améliorer la vitesse d'apparition de clones pendant une étape de sous-clonage en l'absence de pression de sélection. L'ensemble de ces effets bénéfiques permettent une réduction substantielle de la durée de génération de lignées cellulaires tout en augmentant considérablement la productivité des lignées obtenues. Néanmoins, nous avons constaté que la nécessité d'exprimer des niveaux élevés d'IL-17F afin obtenir l'ensemble de ses effets bénéfiques devient une contrainte lors de l'utilisation d'un vecteur d'expression composé de deux promoteurs CMV indépendants pour la co-expression de la cytokine et d'une protéine soluble présentant un intérêt thérapeutique. Afin de mieux comprendre et de surmonter cette limitation, plusieurs études ont été effectuées dans le but de mieux caractériser l'effet de IL-17F au niveau subcellulaire. L'apport régulier en IL-17F recombinante et biologiquement active dans le milieu de culture lors de la sélection de lignées cellulaires ne permet pas de reproduire les effets bénéfiques observés par l'expression endogène d'IL-17F. En outre, nous avons constaté que, lors de l'utilisation du système CHO- GS, l'augmentation d'expression de 1TL-17F est corrélée à un accroissement de l'expression du marqueur de sélection au niveau cellulaire. Ces résultats suggèrent un possible effet d'IL- 17F sur l'activité des promoteurs viraux et ainsi fournissent une preuve directe que les cellules exprimant de haut niveau d'IL-17F sont celles qui en profitent le plus. L'ensemble de ces observations mettrait en avant que l'effet d'IL-17F se ferait selon un mécanisme intracellulaire. Nous avons donc étudié le(s) compartiment(s) spécifique(s) dans lequel IL-17F pourrait exercer son effet. Ce travail a permis de définir IL-17F comme un puissant outil pour l'optimisation des procédés de génération de lignées cellulaires CHO. La caractérisation de cette amélioration de l'effet au niveau moléculaire nous a donné plusieurs indications sur la manière de dépasser les limitations actuelles, ouvrant ainsi la voie au développement d'une technologie viable qui peut être exploitée pars l'industrie biotechnologique.

The impact of agglomeration effects and accessibility on wages

This paper contributes to the empirical literature on the effects of agglomeration and road accessibility on productivity of firms by looking at the case of Spain. We approach productivity indirectly by using individual wages allocated at the NUTS III level. We use a repeated cross-section of individual micro-data for the years 1995, 2002 and 2006. The availability of interprovincial travel time data for each of the three years allows controlling for transport improvements over the period by using a market potential variable. Additionally, agglomeration is approached by employment density and we control for localization economies, human capital externalities and a large set of individual and workplace characteristics. Estimating by instrumental variables, our results show a positive and significant effect of market accessibility on wages and non linear effect for employment density.

Effects of genetic alterations in arbuscular mycorrhizal fungi on plant growth and on their response to a change of host

Abstract :The majority of land plants form the symbiosis with arbuscular mycorrhizal fungi (AMF). The AM symbiosis has existed for hundreds of millions of years but little or no specificity seems to have co- evolved between the partners and only about 200 morphospecies of AMF are known. The fungi supply the plants most notably with phosphate in exchange for carbohydrates. The fungi improve plant growth, protect them against pathogens and herbivores and the symbiosis plays a key role in ecosystem productivity and plant diversity. The fungi are coenocytic, grow clonally and no sexual stage in their life cycle is known. For these reasons, they are presumed ancient asexuals. Evidence suggests that AMF contain populations of genetically different nucleotypes coexisting in a common cytoplasm. Consequently, the nucleotype content of new clonal offspring could potentially be altered by segregation of nuclei at spore formation and by genetic exchange between different AMF. Given the importance of AMF, it is surprising that remarkably little is known about the genetics and genomics of the fungi.The main goal of this thesis was to investigate the combined effects of plant species differences and of genetic exchange and segregation in AMF on the symbiosis. This work showed that single spore progeny can receive a different assortment of nucleotypes compared to their parent and compared to other single spore progeny. This is the first direct evidence that segregation occurs in AMF. We then showed that both genetic exchange and segregation can lead to new progeny that differentially alter plant growth compared to their parents. We also found that genetic exchange and segregation can lead to different development of the fungus during the establishment of the symbiosis. Finally, we found that a shift of host species can differentially alter the phenotypes and genotypes of AMF progeny obtained by genetic exchange and segregation compared to their parents.Overall, this study confirms the multigenomic state of the AMF Glomus intraradices because our findings are possible only if the fungus contains genetically different nuclei. We demonstrated the importance of the processes of genetic exchange and segregation to produce, in a very short time span, new progeny with novel symbiotic effects. Moreover, our results suggest that different host species could affect the fate of different nucleotypes following genetic exchange and segregation in AMF, and can potentially contribute to the maintenance of genetic diversity within AMF individuals. This work brings new insights into understanding how plants and fungi have coevolved and how the genetic diversity in AMF can be maintained. We recommend that the intra-ir1dividual AMF diversity and these processes should be considered in future research on this symbiosis.Résumé :La majorité des plantes terrestres forment des symbioses avec les champignons endomycorhiziens arbusculaires (CEA). Cette symbiose existe depuis plusieurs centaines de millions d'années mais peu ou pas de spécificité semble avoir co-évoluée entre les partenaires et seulement 200 morpho-espèces de CEA sont connues. Le champignon fournit surtout aux plantes du phosphate en échange de carbohydrates. Le champignon augmente la croissance des plantes, les protège contre des pathogènes et herbivores et la symbiose joue un rôle clé dans la productivité des écosystèmes et de la diversité des plantes. Les CEA sont coenocytiques, se reproduisent clonalement et aucune étape sexuée n'est connue dans leur cycle de vie. Pour ces raisons, ils sont présumés comme anciens asexués. Des preuves suggèrent que les CEA ont des populations de nucleotypes différents coexistant dans un cytoplasme commun. Par conséquent, le contenu en nucleotype des nouveaux descendants clonaux pourrait être altéré par la ségrégation des noyaux lors de la fonnation des spores et par l'échange génétique entre différents CEA. Etant donné l'importance des CEA, il est surprenant que si peu soit connu sur la génétique et la génomique du champignon.Le principal but de cette thèse a été d'étudier les effets combinés de différentes espèces de plantes et des mécanismes d'échange génétique et de ségrégation chez les CEA sur la symbiose. Ce travail a montré que chaque nouvelle spore produite pouvait recevoir un assortiment différent de noyaux comparé au parent ou comparé à d'autres nouvelles spores. Ceci est la première preuve directe que la ségrégation peut se produire chez les CEA. Nous avons ensuite montré qu'à la fois l'échange génétique et la ségrégation pouvaient mener à de nouveaux descendants qui altèrent différemment la croissance des plantes, comparé à leurs parents. Nous avons également trouvé que l'échange génétique et la ségrégation pouvaient entraîner des développements différents du champignon pendant l'établissement de la symbiose. Pour finir, nous avons trouvé qu'un changement d'espèce de l'hôte pouvait altérer différemment les phénotypes et génotypes des descendants issus d'échange génétique et de ségrégation, comparé à leurs parents.Globalement, cette étude confirme l'état multigénomique du CEA Glumus intraradices car nous résultats sont possibles seulement si le champignon possède des noyaux génétiquement différents. Nous avons démontrés l'importance des mécanismes d'échange génétique et de ségrégation pour produire en très peu de temps de nouveaux descendants ayant des effets symbiotiques nouveaux. De plus, nos résultats suggèrent que différentes espèces de plantes peuvent agir sur le devenir des nucleotypes après l'échange génétique et la ségrégation chez les CEA, et pourraient contribuer à la maintenance de la diversité génétique au sein d'un même CEA. Ce travail apporte des éléments nouveaux pour comprendre comment les plantes et les champignons ont coévolué et comment la diversité génétique chez les CEA peut être maintenue. Nous recommandons de considérer la diversité génétique intra-individuelle des CEA et ces mécanismes lors de futures recherches sur cette symbiose.

Productivity in southern European small firms: When and how work organization complements process innovation

The aim of this paper is to analyse the effects of human capital, advanced manufacturing technologies (AMT), and new work organizational practices on firm productivity, while taking into account the synergies existing between them. This study expands current knowledge in this area in two ways. First, in contrast with previous works, we focus on AMT and not ICT (information and communication technologies). Second, we use a unique employer-employee data set for small firms in a particular area of southern Europe (Catalonia, Spain). Using a small firm data set, allows us to analyse the particular case of small and medium enterprises, since we cannot assume they have the same characteristics as large firms. The results provide evidence in favor of the complementarity hypothesis between human capital, advanced manufacturing technologies, and new work organization practices, although we show that the complementarity effects depend on what type of work organization practices are used by a firm. For small and medium Catalan firms, the only set of work organization practices that improve the benefits of human capital and technology investment are those practices which are more quality oriented, such as quality circles, problem-solving groups or total quality management.

Schooling in the Network Society : Internet in Primary and Secondary Education. Research report (synthesis document)

Aquest projecte té la intenció d'identificar i analitzar els efectes de la introducció d'Internet a les escoles catalanes (educació primària i secundària). L'objectiu és posar de manifest la manera com s'utilitza la xarxa en aquest àmbit i en quina mesura contribueix a l'aparició, en els centres educatius, d'una nova cultura adaptada a les necessitats de la societat xarxa. Amb aquest propòsit, aquest projecte desplega les seves línies d'anàlisi per a fer atenció al procés d'incorporació d'Internet, principalment, en tres direccions: la pràctica pedagògica, les formes d'organització i gestió dels centres educatius i la seva vinculació amb la comunitat i el territori. Aquesta investigació ha estat desenvolupada pel grup de recerca ENS (Education and Network Society). Amb una perspectiva comparativa, el treball d'aquest grup vol contribuir, sobre la base de dades empíriques, a interpretar la transformació de l'àmbit educatiu no universitari en els paràmetres que estableix, avui dia, la nostra societat.

Effects of Different Postural Conditions on Handwriting Variability

During their career, forensic document examiners will inevitably be confronted with handwriting carried out under unusual conditions (UnC). A questioned document signed on top of a car or on a vertical surface like a wall are two examples. These atypical circumstances may give rise to more variability of the signatures or written words, in particular if the body was in non-traditional writing position without the traditional support. Few studies were devoted to handwriting variability under unusual writing conditions. The current study investigates whether individual variability changes with special writing conditions. In a previous study (Sciacca & al, 2009), we found that eight repetitions were sufficient to obtain a correct estimation of the variance. In the present study, twelve subjects were asked to write two word sets eight times in upper and eight times in lower case, under different conditions : sitting and writing on a horizontal (usual condition UC) or vertical support; and standing, kneeling or laying while writing on a horizontal or vertical support (unusual conditions UnC). Words were written on a pen tablet, normalized in space and time and then averaged. The variance of the eight words was measured under all conditions. Results showed only an increase in variability under the laying and kneeling / vertical UnC. Within the five other postural conditions tested, handwriting was shown to be very stable.

Constraints on the upper Permian to upper Triassic marine carbon isotope curve : case studies from the Tethys

Secular variations of the seawater carbon isotopic composition provide evidence for paleoceanographic and paleoclimatic changes and may serve for chemiostratigraphic correlations. The present study aimed to improve the current knowledge on the Upper Permian and Triassic segment of the Phanerozoic marine carbon isotope curve, whose Triassic part was poorly constrained by previous studies. Profiles of inorganic carbon isotopes are provided for sections from Himalaya (Salt Range, Kashmir, Spiti and Nepal), Oman and North Dobrogea (Romania) on the basis of whole-rock carbonate analysis. The data acquired, together with a literature compilation confirmed that most of the Upper Permian is characterized by high δ13C values (averaging +40/00) but failed to detect a positive excursion as suggested by recent compilations. In the light of these observations, the large drop in δ13C values associated with the end-Permian mass extinction appears to be driven by a sudden transfer of previously stocked 13C depleted carbon, rather than by the overturn of a Late Permian stratified ocean. The Triassic data-set outlines significant secular variations. The best documented is a carbon isotope positive excursion just across the Lower-Middle Triassic boundary, globally developed since it was detected in various paleogeographic settings. It is interpreted to reflect variations in surface ocean chemistry, possibly related to increased primary productivity, at times when the biotic recovery after the end-Permian mass-extinction began to accelerate significantly and when a sharp rise in seawater δ34S values occurred globally. Strontium isotope data obtained from well preserved biogenic phosphates allow a refinement of the Middle Triassic segment of the seawater strontium isotope curve and show a major inflexion point of the seawater strontium isotope curve also near the Lower Triassic - Middle Triassic boundary. These facts suggest that the transition from the Early to the Middle Triassic was a time of revolutionary global change which represented an important step in the evolution of Mesozoic marine environments. A tentative carbon isotope curve for the Upper Permian to Upper Triassic time interval is proposed. Its major features are: ? high but constant δ13C values during the Late Permian ? a sharp drop in δ13C values in the latest Permian ? subsequent recovery of δ13C values ? a short-lived positive excursion across the Early-Middle Triassic boundary ? a gradual rise in δ13C values starting in the Late Ladinian or in the Early Carnian It is foreseen that these fluctuations of the carbon isotope curve may serve as chronostratigraphic markers and further assist in the correlation of Permian and Triassic carbonate deposits.

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The pharmacokinetic profile of imatinib has been assessed in healthy subjects and in population studies among thousands of patients with CML or GIST. Imatinib is rapidly and extensively absorbed from the GI tract, reaching a peak plasma concentration (Cmax) within 1-4 h following administration. Imatinib bioavailability is high (98%) and independent of food intake. Imatinib undergoes rapid and extensive distribution into tissues, with minimal penetration into the central nervous system. In the circulation, it is approximately 95% bound to plasma proteins, principally α1-acid glycoprotein (AGP) and albumin. Imatinib undergoes metabolism in the liver via the cytochrome P450 enzyme system (CYP), with CYP3A4 being the main isoenzyme involved. The N-desmethyl metabolite CGP74588 is the major circulating active metabolite. The typical elimination half-life for imatinib is approximately 14-22 h. Imatinib is characterized by large inter-individual pharmacokinetic variability, which reflects in a wide spread of concentrations observed under standard dosage. Besides adherence, several factors have been shown to influence this variability, especially demographic characteristics (sex, age, body weight and disease diagnosis), blood count characteristics, enzyme activity (mainly CYP3A4), drug interactions, activity of efflux transporters and plasma levels of AGP. Additionally, recent retrospective studies have shown that drug exposure, reflected in either the area under the concentration-time curve (AUC) or more conveniently the trough level (Cmin), correlates with treatment outcomes. Increased toxicity has been associated with high plasma levels, and impaired clinical efficacy with low plasma levels. While no upper concentration limit has been formally established, a lower limit for imatinib Cmin of about 1000 ng/mL has been proposed repeatedly for improving outcomes in CML and GIST patients. Imatinib is licensed for use in chronic phase CML and GIST at a fixed dose of 400 mg once daily (600 mg in some other indications) despite substantial pharmacokinetic variability caused by both genetic and acquired factors. The dose can be modified on an individual basis in cases of insufficient response or substantial toxic effects. Imatinib would, however, meet traditional criteria for a therapeutic drug monitoring (TDM) program: long-term therapy, measurability, high inter-individual but restricted intra-individual variability, limited pharmacokinetic predictability, effect of drug interactions, consistent association between concentration and response, suggested therapeutic threshold, reversibility of effect and absence of early markers of efficacy and toxic effects. Large-scale, evidence-based assessments of drug concentration monitoring are therefore still warranted for the personalization of imatinib treatment.