74 research outputs found

    Leading Global Teams

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    Global teams that are characterized by national, cultural and linguistic heterogeneity and operate in a globally dispersed virtual environment are becoming an established form of organizing work in multinational organizations. As global team leadership research is rather limited, we review the literature on leading multicultural and virtual teams in a global context, focusing on leadership competencies, styles, strategies and modes. We also examine the emergent concepts of biculturalism, global mindset and cultural intelligence with respect to team leaders. Our aim is to add to our knowledge of leading global teams, highlight recent trends and suggest directions for future research. Three themes for global team leadership emerged: leaders as boundary spanners, bridge makers and blenders; people-oriented leadership; and leveraging diversity. We discuss implications for research and practice

    The new millennial global leaders : what a difference a generation makes!

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    Our observations of successful global leaders in much of the literature to date are drawn from individuals who began their careers before the effects of globalization began to be felt signifi-cantly. However, times are changing, along with an understanding about leading and being led by a new generation of workers. In this chapter, we analyse and reflect on our current knowl-edge of the generation born in the global era that is now emerging into positions of leadership. In the popular media, this cohort, born between 1982 and 2004 (Strauss & Howe, 1991),1is known as Generation Y (Sheahan, 2005), Generation Next (Zemke, Raines, & Filipczak, 2000), Generation Net (Tapscott, 2009), Generation Me (Twenge, 2006), Trophy Kids (Alsop, 2008), Generation Whine (Bennet, 2012), and the Millennial Generation (Hershatter & Epstein, 2010; Howe & Strauss, 2000). In this chapter we will use the label ‘Millennial generation’ and refer to individuals as ‘Millennials

    Systematic Evaluation of Voriconazole Pharmacokinetic Models without Pharmacogenetic Information for Bayesian Forecasting in Critically Ill Patients

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    Voriconazole (VRC) is used as first line antifungal agent against invasive aspergillosis. Model-based approaches might optimize VRC therapy. This study aimed to investigate the predictive performance of pharmacokinetic models of VRC without pharmacogenetic information for their suitability for model-informed precision dosing. Seven PopPK models were selected from a systematic literature review. A total of 66 measured VRC plasma concentrations from 33 critically ill patients was employed for analysis. The second measurement per patient was used to calculate relative Bias (rBias), mean error (ME), relative root mean squared error (rRMSE) and mean absolute error (MAE) (i) only based on patient characteristics and dosing history (a priori) and (ii) integrating the first measured concentration to predict the second concentration (Bayesian forecasting). The a priori rBias/ME and rRMSE/MAE varied substantially between the models, ranging from -15.4 to 124.6%/-0.70 to 8.01 mg/L and from 89.3 to 139.1%/1.45 to 8.11 mg/L, respectively. The integration of the first TDM sample improved the predictive performance of all models, with the model by Chen (85.0%) showing the best predictive performance (rRMSE: 85.0%;rBias: 4.0%). Our study revealed a certain degree of imprecision for all investigated models, so their sole use is not recommendable. Models with a higher performance would be necessary for clinical use

    Piperacillin concentration in relation to therapeutic range in critically ill patients - a prospective observational study

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    Background: Piperacillin levels after standard dosing have been shown frequently to be subtherapeutic, especially when renal clearance was augmented. Here, we aimed to determine if piperacillin was in its therapeutic range in a typically heterogeneous intensive care unit patient group, and also to describe target attainment dependent on daily dosage, creatinine clearance, and renal replacement therapy (RRT). Methods: Sixty patients with severe infections were included in this monocentric prospective observational study. Patients received 4.5 g of piperacillin-tazobactam two to three times daily by intermittent infusion depending on renal function according to clinical guidelines. Over 4 days, multiple serum samples (median per patient, 29;in total, 1627) were obtained to determine total piperacillin concentrations using ultra-high-performance liquid chromatography/tandem mass spectrometry. Results: A high heterogeneity of patient characteristics was observed (e.g., on day 1: creatinine clearance 2-233 mL/min and ten patients on RRT). Piperacillin trough levels showed inter-individual variation from 123 to > 1785-fold on different study days. Each day, approximately 50 % and 60 % of the patients had piperacillin levels below the target ranges 1 and 2, respectively [defined for the calculated unbound piperacillin fraction according to the literature as 100 % time above MIC (100 % fT > MIC) (target range 1) and >= 50 % fT > 4 x MIC (target range 2);MIC = 16 mg/L]. Whereas only the minority of patients who received piperacillin-tazobactam three times daily (TID) reached target 1 (38 % on day 1), most patients who received piperacillin-tazobactam only twice daily (BID) because of severely impaired renal function reached this target (100 % on day 1). Patients with RRT had significant higher percentages of fT > MIC. Zero percent, 55 % and 100 % of patients without RRT who received antibiotics TID reached target 1 when creatinine clearance was > 65 mL/min, 30-65 mL/min and < 30 mL/min, respectively. In patients with causative strains only sensitive to piperacillin-tazobactam of all antibiotics given to the patient, piperacillin levels negatively correlated with CRP concentrations of day 4 (p < 0.05). Conclusions: A dosage of 4.5 g piperacillin-tazobactam TID seems to be frequently insufficient in critically ill patients, and also in patients where renal function is mildly to moderately impaired. For these patients, prescription of 4.5 g piperacillin-tazobactam four times daily could be considered

    Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study

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    Background: Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. Methods: A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCRCG). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets 100%T >MIC,50%T >4×MIC) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCRCG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment. Results: Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T >MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T >4×MIC. A hyperbolic relationship between CLCRCG (25–255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C8h) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment (for MIC 8 mg/L, additionally, moderate renal impairment). Conclusions: The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy- and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed. Trial registration Clinicaltrials.gov, NCT01793012 . Registered on 24 January 2013

    A prospective observational study

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    Background: Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. Methods: A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCRCG). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T>MIC, 50%T>4×MIC) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCRCG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non- attainment. Results: Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T>MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T>4×MIC. A hyperbolic relationship between CLCRCG (25–255 ml/ minute) and meropenem serum concentrations at the end of the dosing interval (C8h) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non- attainment (for MIC 8 mg/L, additionally, moderate renal impairment). Conclusions: The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy- and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed

    Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study.

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    Severe infections in intensive care patients show high morbidity and mortality rates. Linezolid is an antimicrobial drug frequently used in critically ill patients. Recent data indicates that there might be high variability of linezolid serum concentrations in intensive care patients receiving standard doses. This study was aimed to evaluate whether standard dosing of linezolid leads to therapeutic serum concentrations in critically ill patients

    Chemical and structural characterization of the native oxide scale on a Mg-based alloy

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    In this study, the structure and composition of the native oxide forming on the basal plane (0001) of Mg-2Al-0.1Ca is investigated by a correlative approach, combining scanning transmission electron microscopy (STEM) and atom probe tomography (APT). Atom probe specimens were prepared conventionally in a Ga focused ion beam (FIB) as well as a Xe plasma FIB in a cryogenic setup and subsequently cleaned in the atom probe to remove surface contamination before oxidation. While thermal energy input from the laser and longer atmospheric exposure time increased the measured hydrogen content in the specimen's apex region, cryo preparation revealed, that the hydrogen uptake in magnesium is independent of the employment of conventional or cryogenic FIB preparation. TEM measurements demonstrated the growth of a (111) MgO oxide layer with 3-4 nm thickness on the basal (0001) plane of the Mg atom probe specimen. APT data further revealed the formation of an aluminum-rich region between bulk Mg and the native oxide. The aluminum enrichment of up to ~20 at.% at the interface is consistent with an inward growth of the oxide scale

    Core-sheath nanofibers as drug delivery system for thermoresponsive controlled release

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    In this work, a smart drug delivery system of core–sheath nanofiber is reported. The core-sheath nanofibers were prepared with thermoresponsive poly-(N-isopropylacrylamide) (PNIPAAm) (as core) and hydrophobic ethylcellulose (EC) (as sheath) by coaxial electrospinning. Analogous medicated fibers were prepared by loading with a model drug ketoprofen (KET). The fibers were cylindrical without phase separation and have visible core-sheath structure as shown by scanning and transmission electron microscopy. X-ray diffraction patterns demonstrated the drug with the amorphous physical form was present in the fiber matrix. Fourier transform infrared spectroscopy analysis was conducted, finding that there were significant intermolecular interactions between KET and the polymers. Water contact angle measurements proved that the core-sheath fibers from hydrophobic transformed into hydrophobic when the temperature reached the lower critical solution temperature. In vitro drug-release study of nanofibers with KET displayed that the coaxial nanofibers were able to synergistically combine the characteristics of the two polymers producing a temperature-sensitive drug delivery system with sustained release properties. In addition, they were established to be non-toxic and suitable for cell growth. These findings show that the core–sheath nanofiber is a potential candidate for controlling drug delivery system
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