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In the Netherlands, two new approaches have been developed for acute and forensic psychiatry, called High and Intensive Care (HIC) and Forensic High and Intensive Care (FHIC). The models provide standards for temporary high-quality clinical care for patients in crisis and combine practices to reduce seclusion. To support the implementation of these approaches, Communities of Practice (CoPs) were created, including peer providers, mental health nurses, psychiatrists and managers. CoPs are increasingly used in healthcare. However, CoPs vary greatly in form and objective, and more insight is needed in the organisation and facilitation of CoPs. Therefore, the aim of this study is to gain insight into the lessons learned and perceived effects of the CoPs. A qualitative approach was used. Data were collected through focus groups (n = 3) with participants in the CoPs, feedback meetings with teams implementing HIC (n = 78) or FHIC (n = 23), and observations by the researchers. Data were analysed thematically. Lessons learned are: 1) create an ambassador role for CoP participants, 2) organize concrete activities, 3) take care of a multidisciplinary composition, and 4) foster shared responsibility and work on sustainability. Perceived effects of the CoPs were: 1) support of HIC and FHIC implementation, 2) creation of a national movement, and 3) further development of the HIC and FHIC approaches. The audits served as an important vehicle to activate the CoPs, and stimulated the implementation of HIC and FHIC. The findings may help others in creating a CoP when it comes to the implementation of best practices and improving healthcare. [ABSTRACT FROM AUTHOR]

We use an argument of Madan and Yor to construct associated submartingales to a class of two-parameter processes that are ordered by increasing convex dominance. This class includes processes whose integrated survival functions are multivariate totally positive of order 2 ( MTP 2 ). We prove that the integrated survival function of an integrable two-parameter process is MTP 2 if and only if it is totally positive of order 2 ( TP 2 ) in each pair of arguments when the remaining argument is fixed. This result cannot be deduced from known results since there are several two-parameter processes whose integrated survival functions do not have interval support. Since the MTP 2 property is closed under several transformations, it allows us to exhibit many other processes having the same total positivity property. [ABSTRACT FROM AUTHOR]

Exposure to aristolochic acid (AA) is associated with human nephropathy and urothelial cancer. The tumour suppressor TP53 is a critical gene in carcinogenesis and frequently mutated in AA-induced urothelial tumours. We investigated the impact of p53 on AAI-induced nephrotoxicity and DNA damage in vivo by treating Trp53(+/+), Trp53(+/−) and Trp53(−/−) mice with 3.5 mg/kg body weight (bw) AAI daily for 2 or 6 days. Renal histopathology showed a gradient of intensity in proximal tubular injury from Trp53(+/+) to Trp53(−/−) mice, especially after 6 days. The observed renal injury was supported by nuclear magnetic resonance (NMR)-based metabonomic measurements, where a consistent Trp53 genotype-dependent trend was observed for urinary metabolites that indicate aminoaciduria (i.e. alanine), lactic aciduria (i.e. lactate) and glycosuria (i.e. glucose). However, Trp53 genotype had no impact on AAI-DNA adduct levels, as measured by 32P-postlabelling, in either target (kidney and bladder) or non-target (liver) tissues, indicating that the underlying mechanisms of p53-related AAI-induced nephrotoxicity cannot be explained by differences in AAI genotoxicity. Performing gas chromatography–mass spectrometry (GC–MS) on kidney tissues showed metabolic pathways affected by AAI treatment, but again Trp53 status did not clearly impact on such metabolic profiles. We also cultured primary mouse embryonic fibroblasts (MEFs) derived from Trp53(+/+), Trp53(+/−) and Trp53(−/−) mice and exposed them to AAI in vitro (50 µM for up to 48 h). We found that Trp53 genotype impacted on the expression of NAD(P)H:quinone oxidoreductase (Nqo1), a key enzyme involved in AAI bioactivation. Nqo1 induction was highest in Trp53(+/+) MEFs and lowest in Trp53(−/−) MEFs; and it correlated with AAI-DNA adduct formation, with lowest adduct levels being observed in AAI-exposed Trp53(−/−) MEFs. Overall, our results clearly demonstrate that p53 status impacts on AAI-induced renal injury, but the underlying mechanism(s) involved remain to be further explored. Despite the impact of p53 on AAI bioactivation and DNA damage in vitro, such effects were not observed in vivo. [ABSTRACT FROM AUTHOR]

Structural and physiological changes that occur as trees grow taller are associated with increased hydraulic constraints on leaf gas exchange, yet it is unclear if leaf-level constraints influence whole-tree growth as trees approach their maximum size. We examined variation in leaf physiology, leaf area to sapwood area ratio ( L/ S), and annual aboveground growth across a range of tree heights in Eucalyptus regnans. Leaf photosynthetic capacity did not differ among upper crown leaves of individuals 61.1-92.4 m tall. Maximum daily and integrated diurnal stomatal conductance ( g) averaged 36 and 34 % higher, respectively, in upper crown leaves of ~60-m-tall, 80-year-old trees than in ~90-m-tall, 300-year-old trees, with larger differences observed on days with a high vapor pressure deficit (VPD). Greater stomatal regulation in taller trees resulted in similar minimum daily leaf water potentials ( Ψ) in shorter and taller trees over a broad range of VPDs. The long-term stomatal limitation on photosynthesis, as inferred from leaf δC composition, was also greater in taller trees. The δC of wood indicated that the bulk of photosynthesis used to fuel wood production in the main trunk and branches occurred in the upper crown. L/ S increased with tree height, especially after accounting for size-independent variation in crown structure across 27 trees up to 99.8 m tall. Despite greater stomatal limitation of leaf photosynthesis in taller trees, total L explained 95 % of the variation in annual aboveground biomass growth among 15 trees measured for annual biomass growth increment in 2006. Our results support a theoretical model proposing that, in the face of increasing hydraulic constraints with height, whole-tree growth is maximized by a resource trade-off that increases L to maximize light capture rather than by reducing L/ S to sustain g. [ABSTRACT FROM AUTHOR]

The dynamics of the cationic, bioelectrical and secretory responses to formycin A were monitored in pancreatic islet cells in order to assess whether this adenosine analogue, which is known to be converted to formycin A 5′-triphosphate in isolated islets, triggers the same sequence of ionic events as that otherwise involved in the process of nutrient-stimulated insulin release and currently attributed to an increase in adenosine 5′-triphosphate (ATP) generation rate. Unexpectedly, formycin A first increasedRb outflow, decreasedCa outflow and inhibited insulin release from prelabelled islets perifused at physiological or higher concentrations of d-glucose. This early inhibitory effect of formycin A upon insulin release coincided, in perforated patch whole-cell recordings, with an initial transient increase of ATP-sensitive K channel activity. A positive secretory response to formycin A, still not associated with any decrease in K conductance, was only observed either immediately after formycin A administration to islets already exposed to glibenclamide or during prolonged exposure to the adenosine analogue. This coincided with an increase of cytosolic Ca concentration in intact B-cells and a greater increase of membrane capacitance in response to depolarization in B-cells examined in the perforated patch whole-cell configuration. The latter stimulation of exocytotic activity could not be attributed, however, to any increase in peak or integrated Ca current. Thus, the mode of action of formycin A, or its 5′-triphosphate ester, in islet cells obviously differs from that currently ascribed to endogenous ATP in the process of nutrient-stimulated insulin release. [ABSTRACT FROM AUTHOR]