Autonomie und Mündigkeit in der Sozialen Arbeit

Autonomie und Mündigkeit sind in der Sozialen Arbeit Ziele, die in dem Band aus drei Richtungen betrachtet werden: erstens bezüglich der Profession, zweitens hinsichtlich des Handelns und drittens im Fokus auf die Nutzer_innen. In den Beiträgen des Bandes werden Autonomie und Mündigkeit in der Sozialen Arbeit dreidimensional betrachtet. Zunächst wird gefragt, inwieweit Soziale Arbeit eine Profession bzw. eine Disziplin ist, die autonom und mündig ihre eigene Identität definieren und abstecken kann. Des Weiteren wird untersucht, ob und in welcher Weise Sozialarbeiter_innen auf der Basis ihrer eigenen professionellen Fachlichkeit agieren und ihre methodischen wie ethischen Kriterien dem Handeln zugrunde legen können. Und schließlich fokussiert der Band die Nutzer_innen sozialarbeiterischer Leistungen, die aus sozialrechtlicher, -politischer und -ethischer Perspektive durch die Soziale Arbeit zur Autonomie und Mündigkeit angeregt werden sollen

Measurement of Hepatic ABCB1 and ABCG2 Transport Activity with [11C]Tariquidar and PET in Humans and Mice

P-Glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) in the canalicular membrane of hepatocytes mediate the biliary excretion of drugs and drug metabolites. To measure hepatic ABCB1 and ABCG2 activity, we performed positron emission tomography (PET) scans with the ABCB1/ABCG2 substrate [11C]tariquidar in healthy volunteers and wild-type, Abcb1a/b(−/−), Abcg2(−/−), and Abcb1a/b(−/−)Abcg2(−/−) mice without and with coadministration of unlabeled tariquidar. PET data were analyzed with a three-compartment pharmacokinetic model. [11C]Tariquidar underwent hepatobiliary excretion in both humans and mice, and tariquidar coadministration caused a significant reduction in the rate constant for the transfer of radioactivity from the liver into bile (by −74% in humans and by −62% in wild-type mice), suggesting inhibition of canalicular efflux transporter activity. Radio-thin-layer chromatography analysis revealed that the majority of radioactivity (>87%) in the mouse liver and bile was composed of unmetabolized [11C]tariquidar. PET data in transporter knockout mice revealed that both ABCB1 and ABCG2 mediated biliary excretion of [11C]tariquidar. In vitro experiments indicated that tariquidar is not a substrate of major hepatic basolateral uptake transporters (SLCO1B1, SLCO1B3, SLCO2B1, SLC22A1, and SLC22A3). Our data suggest that [11C]tariquidar can be used to measure hepatic canalicular ABCB1/ABCG2 transport activity without a confounding effect of uptake transporters

Can inspiratory muscle training improve weaning outcomes in difficult to wean patients? A protocol for a randomised controlled trial (IMweanT study)

INTRODUCTION: Respiratory muscle dysfunction has been associated with failure to wean from mechanical ventilation. It has therefore been hypothesised that these patients might benefit from inspiratory muscle training (IMT). Evidence, however, is thus far limited to data from small, single-centre studies with heterogeneity in inclusion criteria, training modalities and outcomes. The aim of this study is to evaluate the effects of a novel IMT method on weaning outcomes in selected patients with weaning difficulties. METHODS: This study is designed as a double-blind, parallel-group, randomised controlled superiority trial with 1:1 allocation ratio. Patients with weaning difficulties will be randomly allocated into either an IMT group (intervention) or a sham-IMT group (control). Ninetypatients (45 in each group) will be needed to detect a 28% difference in the proportion of weaning success between groups (estimated difference in primary outcome based on previous studies) with a risk for type I error (α) of 5% and statistical power (1-β) of 80%. Patients will perform four sets of 6-10 breaths daily against an external load using a tapered flow resistive loading device (POWERbreathe KH2, HaB International, UK). Training intensity in the intervention group will be adjusted to the highest tolerable load. The control group will train against a low resistance that will not be modified during the training period. Training will becontinued until patients are successfully weaned or for a maximum duration of 28 days. Pulmonary and respiratory muscle function, weaning duration, duration of mechanical ventilation, ventilator-free days and length of stay in the intensive care unit will be evaluated as secondary outcomes. Χ2 tests and analysis of covariance with adjustments for baseline values of respective outcomesas covariates will be used to compare results after the intervention period between groups. ETHICS AND DISSEMINATION: Ethics approval was obtained from the local ethical committee (Ethische Commissie Onderzoek UZ/KU Leuven protocol ID: S60516). Results from this randomised controlled trial will be presented at scientific meetings as abstracts for poster or oral presentations and published in peerreviewed journals. TRIAL STATUS: Enrolment into the study have started in August 2017. Data collection and data analysis are expected to be completed in September 2021. TRIAL REGISTRATION NUMBER: NCT03240263.status: publishe

Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria

Prohibitins comprise an evolutionarily conserved and ubiquitously expressed family of membrane proteins with poorly described functions. Large assemblies of PHB1 and PHB2 subunits are localized in the inner membrane of mitochondria, but various roles in other cellular compartments have also been proposed for both proteins. Here, we used conditional gene targeting of murine Phb2 to define cellular activities of prohibitins. Our experiments restrict the function of prohibitins to mitochondria and identify the processing of the dynamin-like GTPase OPA1, an essential component of the mitochondrial fusion machinery, as the central cellular process controlled by prohibitins. Deletion of Phb2 leads to the selective loss of long isoforms of OPA1. This results in an aberrant cristae morphogenesis and an impaired cellular proliferation and resistance toward apoptosis. Expression of a long OPA1 isoform in PHB2-deficient cells suppresses these defects, identifying impaired OPA1 processing as the primary cellular defect in the absence of prohibitins. Our results therefore assign an essential function for the formation of mitochondrial cristae to prohibitins and suggest a coupling of cell proliferation to mitochondrial morphogenesis

Towards background-free studies of capture reactions in a heavy-ion storage ring

Stored and cooled highly-charged ions offer unprecedented capabilities for precision studies in realm of atomic-, nuclear-structure and astrophysics. In context of the latter, after the successful investigation of the cross section of 96Ru(p,γ) in 2009, in 2016 the first measurement of the 124Xe(p,γ)125Cs reaction was performed at the Experimental Storage Ring (ESR) at GSI

Early mobilization in clinical practice: the reliability and feasibility of the 'Start To Move' Protocol

PURPOSE: The properties of a local Intensive Care Unit early mobilization protocol ('Start To Move As Soon As Possible') in critically ill patients, consisting of an objective diagnostic assessment linked to six treatment levels were evaluated. This study aimed to investigate whether the protocol can be reliably applied by different health-care providers (reliability), to examine the associations between prescribed and delivered treatments (feasibility) and to explore safety and patient satisfaction with the protocol. METHODS: Cross-sectional observational study evaluating the reliability of the protocol between physiotherapist was evaluated with Cohen's kappa, percentage of agreement, and intraclass correlation coefficients in 61 patients. Feasibility was analyzed as agreement between prescribed and delivered treatments with Spearman's rank correlation coefficients in 60 patients. A satisfaction survey was used to evaluate patient satisfaction with the protocol. RESULTS: Excellent agreement was observed between physiotherapists for diagnostic level assignment (Kappa = 0.92), while the majority of the treatment proposals per level showed moderate to substantial agreement between the physiotherapists (Kappa range: 0.40-0.89). Three hundred and thirteen treatments were prescribed. Perfect agreement was observed between prescribed and delivered treatments in level 0 (Spearman's rho 1.00) and excellent associations for levels 1-5 (0.941, 0.995, 0.951, 0.998, and 0.999), respectively. Unwanted safety events rate was 3%. Most patients (92%) were very satisfied with physiotherapy. CONCLUSION: Excellent inter-rater agreement for diagnostic level assignment and moderate to substantial agreement for proposed treatments support the reliability of the protocol. Perfect to excellent associations between prescribed and delivered treatments supports its feasibility. Complications were rare, and most patients were very positive regarding the care provided by physiotherapists during their stay in the ICU.status: publishe

Influence of OATPs on hepatic disposition of erlotinib measured with positron emission tomography

To assess the hepatic disposition of erlotinib, we performed positron emission tomography (PET) scans with [C]erlotinib in healthy volunteers without and with oral pretreatment with a therapeutic erlotinib dose (300mg). Erlotinib pretreatment significantly decreased the liver exposure to [C]erlotinib with a concomitant increase in blood exposure, pointing to the involvement of a carriermediated hepatic uptake mechanism. Using cell lines overexpressing human organic aniontransporting polypeptides (OATPs) 1B1, 1B3, or 2B1, we show that [C]erlotinib is selectively transported by OATP2B1. Our data suggest that at PET microdoses hepatic uptake of [C]erlotinib is mediated by OATP2B1, whereas at therapeutic doses OATP2B1 transport is saturated and hepatic uptake occurs mainly by passive diffusion. We propose that [C]erlotinib may be used as a hepatic OATP2B1 probe substrate and erlotinib as an OATP2B1 inhibitor in clinical drugdrug interaction studies, allowing the contribution of OATP2B1 to the hepatic uptake of drugs to be revealed.(VLID)481531