An on-line solid phase extraction procedure for the routine quantification of caspofungin by liquid chromatography-tandem mass spectrometry

Background: Extensive sets of data are required to investigate the potential use of a therapeutic drug monitoring with individualization of dosage of the antimycotic compound caspofungin. The goal was to develop an improved liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for this aim. Methods: Following protein precipitation, on-line solid phase extraction was performed for sample preparation. As the internal standard compound the veterinary drug tylosin was used. A standard validation protocol was applied. Results: Good reproducibility and accuracy of the method were observed. On-line solid phase extraction resulted in a convenient work-flow and good robustness of the method. Conclusions: This improved LC-MS/MS method was found reliable and convenient. It can be suggested for further work on the clinical pharmacology of caspofungin in the setting of clinical research laboratories

Der Zusammenhang zwischen Kinderkrippeneintritt und sozialemotionalen Auffälligkeiten am Beispiel der Wiener Kinderkrippenstudie (WiKi)

Die Trennung und das Getrenntsein durch einen Krippeneintritt stellt eine schmerzliche Belastung für Kleinkinder dar, da dieser mit erheblicher Angst und Stress verbunden ist. Können Kinder auf ein gutes außerfamiliäres Betreuungsangebot und auf die Unterstüt-zung der Eltern in der Eingewöhnungsphase zurückgreifen, fällt es Kindern leichter, die Trennung und das Getrenntsein zu bewältigen. Sind Kinder mit der Angst auf sich alleine gestellt, da die nötige Unterstützung der Bezugspersonen fehlt, kann dies zu einer Überfor-derung führen. Diese Überforderung kann kindliche Verhaltensauffälligkeiten zur Folge haben, da es Kindern nicht gelingt, die Trennung während des Eingewöhnungsprozesses zu bewältigen. Die Frage, wie Kinder den Übergang von der Familie in die Kinderkrippe in der Eingewöhnungsphase erleben und ob sie diesen bewältigen können, wurde seit 2007 in der Wiener Kinderkrippenstudie (WiKi Studie) anhand von 104 Kindern untersucht. In Anbetracht dieser Thematik wurde in der vorliegenden Arbeit anhand der Daten der Wiener Kinderkrippenstudie ein verhaltensauffälliges Kind namens Kevin und dessen Be-wältigung der Trennung durch den Krippeneintritt untersucht. Die Frage, welcher Zusam-menhang vor dem Hintergrund psychoanalytischer Konzepte zwischen dem Krippenein-tritt, dem kindlichen Verhalten während der Eingewöhnungsphase und Verhaltensauffäl-ligkeiten besteht, steht im Zentrum dieser Arbeit. Um diese Frage zu beantworten, sollte eine quantitativ-empirische Berechnung anhand von Korrelationen durchgeführt werden. Die Anzahl der in der WiKi-Studie untersuchten, verhaltensauffälligen Kinder war für die quantitative Überprüfung zu gering, woraufhin die qualitativ-empirische Einzelfallanalyse herangezogen wurde. Die Einzelfallanalyse Kevin wurde unter Bezugnahme vieler, in der WiKi Studie eingesetzter, Untersuchungsinstrumente und dessen Daten dargestellt (CBCL/C-TRF, Videoanalyse, „Familien-Situation“ Bogen, „Krippen-Situation“ Bogen, Attachment Q-Sort (AQS), Toddler Temperament Scale (TTS), Fragebogen zur Erhebung lebensverändernder Umstände in der Familie bis sechs Monate nach Krippeneintritt). Durch die Videoanalysedaten konnte auf den Eingewöhnungsprozess von Kevin rückgeschlossen werden. Als Ergebnis resultierte, dass es Kevin nicht möglich war, die Trennung durch den Krippeneintritt in der Eingewöhnungsphase zu bewältigen. Die Datenanalyse der weiteren Untersuchungsinstrumente durch psychoanalytische Konzepte ergab, dass eine nicht gelungene Bewältigung des Krippeneintrittes in Zusammenhang mit auffälligen sozialemotional kindlichen Verhaltensweisen stehen kann, dass aber sehr wohl auch andere Faktoren und dessen Zusammenspiel ausschlaggebend für Verhaltensauffälligkeiten sein können.The separation and the separateness by joining a crèche is a painful burden for infants , because it is associated with fierce anxiety and stress. If children can draw on a good extra-familial care offer and on a parental support during their settling in period, children are more likely to cope with their separation and their separateness. Children, who are on their own with anxiety, due to a lacking but necessary support of caregivers, can be mentally overloaded. These mental overloads can result in behavioural problems because children are not able to cope with the separation during this acclimatisation process. The question how children experience the transition from their familial surrounding to the crèche during the settling in period and whether they can cope with it, has been examined since 2007 in the “Toddlers Adjustment to Out-of-Home Care – Die Wiener Kinderkrippenstudie (WiKi)” on the basis of 104 children. In view of these subject matters a child named Kevin displaying behavioural problems and his coping with the separation by joining a crèche has been investigated in this study using data from the Toddlers Adjustment to Out-of-Home Care. The question of the relation in context of psychoanalytic concepts between the joining of a crèche, the child's behaviour during the settling in period and behavioural problem is the focus of this thesis. To answer these questions, quantitative-empirical calculations based on correlations are performed. The number of examined children showing behavioural problems was too small for a quan-titative validation, whereat the qualitative empirical single case analysis was used. The single case study Kevin was presented in reference to many examination mechanisms in-serted in the WiKi study and its data (CBCL / C-TRF, video analysis, standardised ques-tionnaires, Attachment Q-Sort (AQS) Toddler Temperament Scale (TTS), questionnaires for the inquiry of life-changing circumstances in the family until six months after joining the crèche). The process of Kevin’s settling in the crèche could be inferred from the video analysis data. Consequential Kevin was not able to cope with the separation by joining the crèche in the settling in period. The data analysis of further investigation mechanisms by psychoanalytic concepts revealed that a failed entrance into the crèche can be connected with pathological socio-emotional childlike behaviour, but as well different factors and their interactions may be crucial for behavioural problems

FROM ISOLATION TO COLLABORATION - HOW THE INCREASING DIFFUSION OF MOBILE DEVICES HAS CHANGED PRACTICES OF KNOWLEDGE SHARING IN NON-OFFICE SETTINGS

The increasing diffusion of mobile devices such as smartphones or tablets has not only revolutionized how people communicate with each other, but has also changed work practices and the way employ-ees share knowledge. Knowledge management studies have to date mainly focused on office settings but paid little attention to non-office workplace settings. However, the use of mobile devices also changes the way employees can be supported and support each other in non-office settings and thus create new application areas for knowledge management. In this research, we applied a three step qualitative inquiry with 36 experts in the construction sector to investigate how the increasing diffu-sion of mobile devices has affected existing work practices that are associated with knowledge sharing in non-office settings. We found that the use of mobile devices helped to transform isolated work prac-tices into collaborative work practices, thereby reducing the spatial, temporal, contextual, and social barriers to knowledge sharing. As such, an increase in connectivity can be seen as an indicator for potential development of increased collaboration across work sites. We conclude the paper with a dis-cussion of implications for organizations concerning the support of knowledge sharing in such settings and an outlook on future work

EEG microstates as biomarker for psychosis in ultra-high-risk patients

Resting-state EEG microstates are brief (50-100 ms) periods, in which the spatial configuration of scalp global field power remains quasi-stable before rapidly shifting to another configuration. Changes in microstate parameters have been described in patients with psychotic disorders. These changes have also been observed in individuals with a clinical or genetic high risk, suggesting potential usefulness of EEG microstates as a biomarker for psychotic disorders. The present study aimed to investigate the potential of EEG microstates as biomarkers for psychotic disorders and future transition to psychosis in patients at ultra-high-risk (UHR). We used 19-channel clinical EEG recordings and orthogonal contrasts to compare temporal parameters of four normative microstate classes (A-D) between patients with first-episode psychosis (FEP; n = 29), UHR patients with (UHR-T; n = 20) and without (UHR-NT; n = 34) later transition to psychosis, and healthy controls (HC; n = 25). Microstate A was increased in patients (FEP & UHR-T & UHR- NT) compared to HC, suggesting an unspecific state biomarker of general psychopathology. Microstate B displayed a decrease in FEP compared to both UHR patient groups, and thus may represent a state biomarker specific to psychotic illness progression. Microstate D was significantly decreased in UHR-T compared to UHR-NT, suggesting its potential as a selective biomarker of future transition in UHR patients

NOT JUST ANOTHER TYPE OF RESISTANCE – TOWARDS A DEEPER UNDERSTANDING OF SUPPORTIVE NON-USE

Research on information system (IS) adoption and resistance has accumulated substantial theoretical and managerial knowledge. Surprisingly, the paradox that end users support and at the same time resist use of an IS has received relatively little attention. The investigation of this puzzle, however, is important to complement our understanding of resistant behaviours and consequently to strengthen the explanatory power of extant theoretical constructs on IS resistance. We investigate an IS project within the healthcare sector in the UK in which end-users, who were heavily involved during the de-sign, implementation and roll out, expressed their support for the system, while simultaneously showing resistance. To examine this behaviour in detail, we applied Q methodology. As a result, we identified three different groups: (1) The convinced connector, waiting for collaborators. (2) The savvy explorer, sceptical about the tools’ benefits. (3) The ambivalent follower, overwhelmed by complexity. While the behaviour is similar across all three groups, the reasons for not using the system differ significantly. Based on these groups, as our main contribution, we explain the paradox of supportive non-use. We further add a fine grained understanding of supportive non-use to the existing types of IS resistance

In vivo investigation of open-pored magnesium scaffolds LAE442 with different coatings in an open wedge defect

The magnesium alloy LAE442 showed promising results as a bone substitute in numerous studies in non-weight bearing bone defects. This study aimed to investigate the in vivo behavior of wedge-shaped open-pored LAE442 scaffolds modified with two different coatings (magnesium fluoride (MgF2, group 1)) or magnesium fluoride/calcium phosphate (MgF2/CaP, group 2)) in a partial weight-bearing rabbit tibia defect model. The implantation of the scaffolds was performed as an open wedge corrective osteotomy in the tibia of 40 rabbits and followed for observation periods of 6, 12, 24, and 36 weeks. Radiological and microcomputed tomographic examinations were performed in vivo. X-ray microscopic, histological, histomorphometric, and SEM/EDS analyses were performed at the end of each time period. µCT measurements and X-ray microscopy showed a slight decrease in volume and density of the scaffolds of both coatings. Histologically, endosteal and periosteal callus formation with good bridging and stabilization of the osteotomy gap and ingrowth of bone into the scaffold was seen. The MgF2 coating favored better bridging of the osteotomy gap and more bone-scaffold contacts, especially at later examination time points. Overall, the scaffolds of both coatings met the requirement to withstand the loads after an open wedge corrective osteotomy of the proximal rabbit tibia. However, in addition to the inhomogeneous degradation behavior of individual scaffolds, an accumulation of gas appeared, so the scaffold material should be revised again regarding size dimension and composition

In vivo investigation of open-pored magnesium scaffolds LAE442 with different coatings in an open wedge defect

The magnesium alloy LAE442 showed promising results as a bone substitute in numerous studies in non-weight bearing bone defects. This study aimed to investigate the in vivo behavior of wedge-shaped open-pored LAE442 scaffolds modified with two different coatings (magnesium fluoride (MgF2, group 1)) or magnesium fluoride/calcium phosphate (MgF2/CaP, group 2)) in a partial weight-bearing rabbit tibia defect model. The implantation of the scaffolds was performed as an open wedge corrective osteotomy in the tibia of 40 rabbits and followed for observation periods of 6, 12, 24, and 36 weeks. Radiological and microcomputed tomographic examinations were performed in vivo. X-ray microscopic, histological, histomorphometric, and SEM/EDS analyses were performed at the end of each time period. µCT measurements and X-ray microscopy showed a slight decrease in volume and density of the scaffolds of both coatings. Histologically, endosteal and periosteal callus formation with good bridging and stabilization of the osteotomy gap and ingrowth of bone into the scaffold was seen. The MgF2 coating favored better bridging of the osteotomy gap and more bone-scaffold contacts, especially at later examination time points. Overall, the scaffolds of both coatings met the requirement to withstand the loads after an open wedge corrective osteotomy of the proximal rabbit tibia. However, in addition to the inhomogeneous degradation behavior of individual scaffolds, an accumulation of gas appeared, so the scaffold material should be revised again regarding size dimension and composition

Magnesium Alloys for Open-Pored Bioresorbable Implants

If bone defects occur, the body’s own healing mechanism can close them below a critical size; for larger defects, bone autografts are used. These are typically cut from the same person’s hip in a second surgery. Consequently, the risk of complications, such as inflammations, rises. To avoid the risks resulting from the second surgery, absorbable, open-pored implants can be used. In the present study, the suitability of different magnesium alloys as absorbable porous bone substitute material has been investigated. Using the investment casting process with its design flexibility, the implant’s structure can be adapted to the ideal pore geometry with respect to bone ingrowth behavior. Different magnesium alloys (Mg-La2, LAE442, and ZX61) were studied and rated in terms of their degradation rate, bone ingrowth behavior, biocompatibility, and resorbability of the individual alloying elements

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

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

Extracellular calcium reduction strongly increases the lytic capacity of pneumolysin from streptococcus pneumoniae in brain tissue

Background. Streptococcus pneumoniae causes serious diseases such as pneumonia and meningitis. Its major pathogenic factor is the cholesterol-dependent cytolysin pneumolysin, which produces lytic pores at high concentrations. At low concentrations, it has other effects, including induction of apoptosis. Many cellular effects of pneumolysin appear to be calcium dependent. Methods. Live imaging of primary mouse astroglia exposed to sublytic amounts of pneumolysin at various concentrations of extracellular calcium was used to measure changes in cellular permeability (as judged by lactate dehydrogenase release and propidium iodide chromatin staining). Individual pore properties were analyzed by conductance across artificial lipid bilayer. Tissue toxicity was studied in continuously oxygenated acute brain slices. Results. The reduction of extracellular calcium increased the lytic capacity of the toxin due to increased membrane binding. Reduction of calcium did not influence the conductance properties of individual toxin pores. In acute cortical brain slices, the reduction of extracellular calcium from 2 to 1 mM conferred lytic activity to pathophysiologically relevant nonlytic concentrations of pneumolysin. Conclusions. Reduction of extracellular calcium strongly enhanced the lytic capacity of pneumolysin due to increased membrane binding. Thus, extracellular calcium concentration should be considered as a factor of primary importance for the course of pneumococcal meningitis