Ambidexterity as practice : individual ambidexterity through paradoxical practices

Following the turn to practice in organization theory and the emerging interest in the microfoundations of ambidexterity, understanding the role of individuals in realizing ambidexterity approaches becomes crucial. Drawing insights from Greek philosophy on paradoxes, and practice theory on paradoxes and ambidexterity, we propose a view of individual ambidexterity grounded in paradoxical practices. Existing conceptualizations of ambidexterity are largely based on separation strategies. Contrary to this perspective, we argue that individual ambidexterity can be accomplished via paradoxical practices that renegotiate or transcend boundaries of exploration and exploitation. We identify three such paradoxical practices at the individual level that can advance understanding of ambidexterity: engaging in “hybrid tasks,” capitalizing cumulatively on previous learning, and adopting a mindset of seeking synergies between the competing demands of exploration and exploitation

Managing the tensions of innovation and efficiency in the pursuit of organizational ambidexterity

Whereas organizational ambidexterity is increasingly gaining ground in organizational theory, key issues regarding how ambidexterity is conceptualized, achieved and sustained offer partial insights or remain unexplored. Current approaches to ambidexterity so far have followed rather static and single level approaches to ambidexterity, without further exploring the underlying mechanisms of how ambidexterity is pursued in practice and through which mechanism and processes tensions are managed. In order to address this gap, this research adopts a holistic approach to the study of ambidexterity exploring tensions at different organizational levels. Based on a case study research in two organizations in pursuit of ambidexterity this research brings forward a view of ambidexterity that is complex and dynamic, as it involves the co-existence of different tensions and modes of balancing within different organizational groups. Research findings contribute to the study of ambidexterity at two main levels: tension manifestation (which tensions arise at each organizational group) and tension management (the mode of balance pursued in each case). Following a micro-level approach to the research of ambidexterity, findings bring forward the role of organizational actors in the management of tensions: based on how individuals perceived tensions (as complementary, conflicting, or interrelated), their organizational level and their strategic orientation different modes of balancing were pursued. As a result this research contributes to the theory of ambidexterity by identifying a path dependent process of managing tensions based on how individuals perceive the nature of the tensions. As literature on ambidexterity is shifting towards the importance of agency, gaining this understanding is a crucial step towards how ambidexterity is achieved

In pursuit of ambidexterity : managerial reactions to innovation-efficiency tensions

Whereas tensions arising from the pursuit of ambidexterity have been documented, how these are interpreted and managed by actors themselves remains largely unexplored. Based on in-depth case research in a large Scandinavian based telecommunications organization pursuing ambidexterity, we identify a path-dependent process of tension interpretation and tension management at different levels of the organization. Our findings suggest that in the context of an ambidextrous strategy, actors are actively involved in managing arising tensions based on their differing interpretations of these tensions (where ambidextrous demands are seen as complementary, conflicting or interrelated). We find that these interpretations are influenced by actors’ strategic orientation and organizational level. Our study extends understanding of the pursuit of ambidexterity in practice, offering a pluralist, path-dependent perspective of how actors perceive and deal with ambidexterity tensions

D-optimal design of a pediatric pharmacokinetic study of a fixed dose combination product of rifampicin-pyrazinamide-isoniazid for the treatment of tuberculosis

Ο σκοπός αυτής της εργασίας είναι να σχεδιαστεί μια παιδιατρική φαρμακοκινητική μελέτη αραιής δειγματοληψίας ενός φαρμακευτικού σκευάσματος σταθερού συνδυασμού δόσης, ισονιαζίδης, ριφαμπικίνης και πυραζιναμίδης για την θεραπεία της φυματίωσης. Θεωρείται ότι θα δοθεί μια μοναδική χορήγηση του φαρμακευτικού σκευάσματος σε δυο κοορτές των πενήντα(50) παιδιών η καθεμία. Μη γραμμικά μοντέλα μικτών επιδράσεων χρησιμοποιήθηκαν προκείμενου να περιγράψουν την δομή καθενός από τα φαρμακευτικά μοντέλα. Καθορίσαμε ένα μοναδικό δειγματοληπτικό σχήμα για τα τρία φάρμακα, έτσι ώστε οι παράμετροι των φαρμακοκινητικών μοντέλων να εκτιμηθούν με υψηλή ακρίβεια. Eφαρμόστηκε μια μέθοδος βασισμένη στον Πίνακα Πληροφορίας του Fisher (Fisher Information Matrix) για μη γραμμικά μοντέλα μικτών επιδράσεων προκειμένου να βελτιστοποιηθούν οι χρόνοι δειγματοληψίας αποκτώντας αποτελεσματικές εκτιμήσεις των παραμέτρων. Η προσέγγιση αυτή βασίζεται στην ανισότητα του Rao-Cramer κατά την οποία o αντίστροφος του Πίνακα Πληροφορίας του Fisher είναι το κάτω φράγμα του πίνακα διασποράς- συν διασποράς κάθε αμερόληπτού εκτιμητή των παραμέτρων. Το κριτήριο που χρησιμοποιήθηκε για την βελτιστοποίηση είναι το D-βέλτιστο. Ένας σχεδιασμός θεωρείται D-βέλτιστος εάν μεγιστοποιεί την ορίζουσα του Πίνακα Πληροφοριών του Fisher. Ο αλγόριθμος particle swarm optimization (PSO) εφαρμόστηκε για την διαδικασία της βελτιστοποίησης καθώς και όλη η εφαρμογή διεξήχθηκε στο προγραμματιστικό πακέτο MATLAB. Ο τελικός σχεδιασμός αξιολογήθηκε μέσω προσομοιώσεων και εκτιμήσεων στο πακέτο NONMEM. Bootstrap, Visual predictive check plots και γραφήματα καλής προσαρμογής δημιουργήθηκαν. Τελικά σχεδιάστηκε, μια φαρμακοκινητική μελέτη με 4 δείγματα αίματος ανά ασθενή. Οι βέλτιστοι χρόνοι δειγματοληψίας για την πρώτη κοορτή είναι στις 0.10 , 0.13 ,0.55 και 4.28 ώρες και οι βέλτιστοι χρόνοι δειγματοληψίας για την δεύτερη κοορτή είναι στις 0.57 , 1.38, 2.25 and 6 ώρες. Η αξιολόγηση των τριών φαρμακοκινητικών μοντέλων έδειξε ακριβή αποτελέσματα, όσο αναφορά τις εκτιμήσεις των παραμέτρων. Κλείνοντας, εάν αυτή η κλινική μελέτη πραγματοποιηθεί, τότε το φαρμακευτικό αυτό σκεύασμα σταθερού συνδυασμού δόσης για την θεραπεία της φυματίωσης, θα μπορεί να πάρει έγκριση για άδεια κυκλοφορίας στην Ευρώπη και την Αμερική, το οποίο μέχρι τώρα δεν είναι διαθέσιμο.The objective of this dissertation was to design a sparse sampling pediatric pharmacokinetic study for a fixed dose combination product of isoniazid (Η), rifampicin (R) and pyrazinamide (Z) for the treatment of tuberculosis. A single dose of FDC tablet was supposed to be given into two cohorts of fifty (50) children each. Non-linear mixed effects models were used to describe the structure of each drug model. We determined a unique optimal sampling schedule for the three drugs, such that the parameters of the PK models of each drug are estimated with high precision. We applied a method based on an expression for the Fisher Information Matrix (FIM) for non-linear mixed effects to improve the sampling design so as to obtain efficient parameter estimates. The approach is based on Rao-Cramer inequality which states that the inverse of FIM is the lower bound of the variance-covariance matrix of any unbiased estimators of the parameters. The criterion used for the optimization is D-optimality; a design is considered D-optimal if it maximizes the determinant of the Fisher information matrix. The particle swarm optimization (PSO) algorithm was applied for the optimization procedure while all implementation was conducted in MATLAB. The final design was evaluated by simulations and estimation with NONMEM. Bootstrap, Visual Predictive Check (VPC) plots and Goodness of fit plots were generated. A pharmacokinetic study with 4 blood samples per subject was eventually designed. The optimal blood sampling times for the first cohort is0.10h, 0.13h, 0.55h and 4.28h and optimal blood sampling times for Cohort 2 is 0.57 h, 1.38h, 2.25h and 6h.The evaluation of the 3 pharmacokinetic models showed accurate results, as regards the parameter estimates. Finally, if the clinical trial that we designed is implemented, it could be used for taking Marketing Authorization Approval of first-line paediatric fixed dose combination product for the treatment of tuberculosis in Europe and USΑ, which is currently unavailable

PTH Signaling During Exercise Contributes to Bone Adaptation

Improving the structural integrity of bone reduces fracture risk and development of osteoporosis later in life. Exercise can increase the mechanical properties of bone, and this increase is often attributed to the dynamic loading created during exercise. However, the increase in systemic parathyroid hormone (PTH) levels during exercise gives reason to hypothesize that PTH signaling also regulates bone adaptation in response to exercise. Therefore, the first aim of this study was to establish the impact PTH signaling has on bone adaptation during exercise by inhibiting PTH signaling with PTH(7‐34); the second aim was to determine whether increasing PTH levels during exercise with PTH(1‐34) can augment bone adaptation. Thirty minutes after a single bout of running on a treadmill, mice exhibited a twofold increase in systemic PTH levels. Under the same exercise regimen, the influence of PTH signaling on bone adaptation during exercise was then evaluated in mice after 21 consecutive days of exercise and treatment with PTH(7‐34), PTH(1‐34), or vehicle. Exercise alone caused a significant increase in trabecular bone volume with adaptation to a more platelike structure, which was inhibited with PTH(7‐34) during exercise. Changes in structural‐level and tissue‐level mechanical properties during exercise occurred in the absence of significant changes to cortical bone geometry. Inhibition of PTH signaling during exercise attenuated the changes in structural‐level mechanical properties, but not tissue‐level properties. Enhanced PTH signaling during exercise with PTH(1‐34) increased trabecular and cortical bone volume, but had little effect on the structural‐level and tissue‐level mechanical properties compared to exercise alone. Our study is the first to demonstrate that bone adaptation during exercise is not only a function of dynamic loading, but also PTH release, and that PTH signaling contributes differently at the structural and tissue levels. © 2015 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111785/1/jbmr2432.pd

Suppression of zinc finger protein 467 alleviates osteoporosis through promoting differentiation of adipose derived stem cells to osteoblasts

Osteoblast and adipocyte are derived from common mesenchymal progenitor cells. The bone loss of osteoporosis is associated with altered progenitor differentiation from an osteoblastic to an adipocytic lineage. In this study, a comparative analysis of gene expression profiling using cDNA microarray and realtime-PCR indicated that Zinc finger protein 467 (Zfp467) involved in adipocyte and osteoblast differentiation of cultured adipose derived stem cells (ADSCs). Our results showed that RNA interference for Zfp467 in ADSCs inhibited adipocyte formation and stimulated osteoblast commitment. The mRNA levels of osteogenic and adipogenic markers in ADSCs were regulated by si-Zfp467. Zfp467 RNAi in ADSCs could restore bone function and structure in an ovariectomized (OVX)-induced osteoporotic mouse model. Thus Zfp467 play an important role in ADSCs differentiation to adipocyte and osteoblast. This has relevance to therapeutic interventions in osteoporosis, including si-Zfp467-based therapies currently available, and may be of relevance for the use of adipose-derived stem cells for tissue engineering

Now, switch! Individuals’ responses to imposed switches between exploration and exploitation

Individual ambidexterity is an important micro-foundation of organizational ambidexterity. However, switching back-and-forth between exploration and exploitation can be challenging for individuals. Prior research has mostly focused on bottom-up approaches to stimulating individual ambidexterity, yet many organizations are characterized by greater top-down control. Exercising control may complicate the pursuit of individual ambidexterity because it amplifies switching resistance. We draw on an observational study of facilitated strategy workshops to explore the role of switching resistance and steps that can be taken to deal with it in top-down settings. Our findings suggest that imposing switches on individuals tends to trigger a distinct pattern of behavioral responses. Furthermore, we find that increasing control and offering emotional support can reduce switching resistance and help individuals execute ambidextrous work tasks. Our study contributes to the literature on individual ambidexterity by extending it from bottom-up to top-down settings. Specifically, we identify emotional, cognitive and behavioral drivers of switching resistance and unpack the process leading up to resistance. Furthermore, we identify organizational measures relevant for addressing such resistance and resolving ambidexterity at the individual level.info:eu-repo/semantics/publishedVersio

Mechanical Strain Regulates Osteoblast Proliferation through Integrin-Mediated ERK Activation

Mechanical strain plays a critical role in the proliferation, differentiation and maturation of bone cells. As mechanical receptor cells, osteoblasts perceive and respond to stress force, such as those associated with compression, strain and shear stress. However, the underlying molecular mechanisms of this process remain unclear. Using a four-point bending device, mouse MC3T3-E1 cells was exposed to mechanical tensile strain. Cell proliferation was determined to be most efficient when stimulated once a day by mechanical strain at a frequency of 0.5 Hz and intensities of 2500 µε with once a day, and a periodicity of 1 h/day for 3 days. The applied mechanical strain resulted in the altered expression of 1992 genes, 41 of which are involved in the mitogen-activated protein kinase (MAPK) signaling pathway. Activation of ERK by mechanical strain promoted cell proliferation and inactivation of ERK by PD98059 suppressed proliferation, confirming that ERK plays an important role in the response to mechanical strain. Furthermore, the membrane-associated receptors integrin β1 and integrin β5 were determined to regulate ERK activity and the proliferation of mechanical strain-treated MC3T3-E1 cells in opposite ways. The knockdown of integrin β1 led to the inhibition of ERK activity and cell proliferation, whereas the knockdown of integrin β5 led to the enhancement of both processes. This study proposes a novel mechanism by which mechanical strain regulates bone growth and remodeling

Mechanobiological Modulation of Cytoskeleton and Calcium Influx in Osteoblastic Cells by Short-Term Focused Acoustic Radiation Force

Mechanotransduction has demonstrated potential for regulating tissue adaptation in vivo and cellular activities in vitro. It is well documented that ultrasound can produce a wide variety of biological effects in biological systems. For example, pulsed ultrasound can be used to noninvasively accelerate the rate of bone fracture healing. Although a wide range of studies has been performed, mechanism for this therapeutic effect on bone healing is currently unknown. To elucidate the mechanism of cellular response to mechanical stimuli induced by pulsed ultrasound radiation, we developed a method to apply focused acoustic radiation force (ARF) (duration, one minute) on osteoblastic MC3T3-E1 cells and observed cellular responses to ARF using a spinning disk confocal microscope. This study demonstrates that the focused ARF induced F-actin cytoskeletal rearrangement in MC3T3-E1 cells. In addition, these cells showed an increase in intracellular calcium concentration following the application of focused ARF. Furthermore, passive bending movement was noted in primary cilium that were treated with focused ARF. Cell viability was not affected. Application of pulsed ultrasound radiation generated only a minimal temperature rise of 0.1°C, and induced a streaming resulting fluid shear stress of 0.186 dyne/cm2, suggesting that hyperthermia and acoustic streaming might not be the main causes of the observed cell responses. In conclusion, these data provide more insight in the interactions between acoustic mechanical stress and osteoblastic cells. This experimental system could serve as basis for further exploration of the mechanosensing mechanism of osteoblasts triggered by ultrasound