The ‘values journey’ of nursing and midwifery students selected using multiple mini interviews; Year One findings

Aim: to explore how adult, child and mental health nursing and midwifery students, selected using multiple mini interviews, describe their ‘values journey’ following exposure to the clinical practice environment. Background: Values based recruitment incorporates assessment of healthcare students’ personal values using approaches like multiple mini interviews. Students’ experience of adjustment to their values during their programme is conceptualised as a ‘values journey’. The impact of VBR in alleviating erosion of personal values is unclear. Design A cross-professional longitudinal cohort study was commenced at one university in England in 2016 with data collection points at the end of years one, two and three. Non-probability consecutive sampling resulted in 42 healthcare students (8 adult, 8 child and 9 mental health nursing and 17 midwifery students) taking part. Methods: Six semi-structured focus groups were conducted at the end of participants’ Year One (DC1). Data analysis incorporated inductive and deductive approaches in a hybrid synthesis. Findings: Participants described a ‘values journey’ where their values, particularly communication, courage and wanting to make a difference, were both challenged and retained. Participants personal journeys also acknowledged the: ‘courage it takes to use values’; ‘reality of values in practice’ and ‘need for self-reflection on values’. Conclusion: A ‘values journey’ may begin early in healthcare student’s education programme. This is important to recognise so that appropriate measures are implemented to support students across higher education and clinical practice. Consideration should also be given to the values incorporated in values based recruitment to ensure their fitness for purpose

Delineation of RAID1, the RACK1 interaction domain located within the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5

Background The cyclic AMP specific phosphodiesterase, PDE4D5 interacts with the β-propeller protein RACK1 to form a signaling scaffold complex in cells. Two-hybrid analysis of truncation and mutant constructs of the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5 were used to define a domain conferring interaction with the signaling scaffold protein, RACK1. Results Truncation and mutagenesis approaches showed that the RACK1-interacting domain on PDE4D5 comprised a cluster of residues provided by Asn-22/Pro-23/Trp-24/Asn-26 together with a series of hydrophobic amino acids, namely Leu-29, Val-30, Leu-33, Leu-37 and Leu-38 in a 'Leu-Xaa-Xaa-Xaa-Leu' repeat. This was done by 2-hybrid analyses and then confirmed in biochemical pull down analyses using GST-RACK1 and mutant PDE4D5 forms expressed in COS cells. Mutation of Arg-34, to alanine, in PDE4D5 attenuated its interaction with RACK1 both in 2-hybrid screens and in pull down analyses. A 38-mer peptide, whose sequence reflected residues 12 through 49 of PDE4D5, bound to RACK1 with similar affinity to native PDE4D5 itself (Ka circa 6 nM). Conclusions The RACK1 Interaction Domain on PDE4D5, that we here call RAID1, is proposed to form an amphipathic helical structure that we suggest may interact with the C-terminal β-propeller blades of RACK1 in a manner akin to the interaction of the helical G-γ signal transducing protein with the β-propeller protein, G-β

Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels

Disrupted-in-schizophrenia 1 (DISC1) is a genetic susceptibility factor for schizophrenia and related severe psychiatric conditions. DISC1 is a multifunctional scaffold protein that is able to interact with several proteins, including the independently identified schizophrenia risk factor phosphodiesterase-4B (PDE4B). Here we report that the 100 kDa full-length DISC1 isoform (fl-DISC1) can bind members of each of the four gene, cAMP-specific PDE4 family. Elevation of intracellular cAMP levels, so as to activate protein kinase A, caused the release of PDE4D3 and PDE4C2 isoforms from fl-DISC1 while not affecting binding of PDE4B1 and PDE4A5 isoforms. Using a peptide array strategy, we show that PDE4D3 binds fl-DISC1 through two regions found in common with PDE4B isoforms, the interaction of which is supplemented because of the presence of additional PDE4B-specific binding sites. We propose that the additional binding sites found in PDE4B1 underpin its resistance to release during cAMP elevation. We identify, for the first time, a functional distinction between the 100 kDa long DISC1 isoform and the short 71 kDa isoform. Thus, changes in the expression pattern of DISC1 and PDE4 isoforms offers a means to reprogram their interaction and to determine whether the PDE4 sequestered by DISC1 is released after cAMP elevation. The PDE4B-specific binding sites encompass point mutations in mouse Disc1 that confer phenotypes related to schizophrenia and depression and that affect binding to PDE4B. Thus, genetic variation in DISC1 and PDE4 that influence either isoform expression or docking site functioning may directly affect psychopathology

The reliability and validity of multiple mini interviews (MMIs) in values based recruitment to nursing, midwifery and paramedic practice: Findings from an evaluation study

Background: Universities in the United Kingdom (UK) are required to incorporate values based recruitment (VBR) into their healthcare student selection processes. This reflects an international drive to strengthen the quality of healthcare service provision. This paper presents novel findings in relation to the reliability and predictive validity of multiple mini interviews (MMIs); one approach to VBR widely being employed by universities. Objectives: To examine the reliability (internal consistency) and predictive validity of MMIs using end of Year One practice outcomes of under-graduate pre-registration adult, child, mental health nursing, midwifery and paramedic practice students. Design: Cross-discipline evaluation study. Setting: One university in the United Kingdom. Participants: Data were collected in two streams: applicants to A) The September 2014 and 2015 Midwifery Studies programmes; B) September 2015 adult; Child and Mental Health Nursing and Paramedic Practice programmes. Fifty-seven midwifery students commenced their programme in 2014 and 69 in 2015; 47 and 54 agreed to participate and completed Year One respectively. 333 healthcare students commenced their programmes in September 2015. Of these, 281 agreed to participate and completed their first year (180 adult, 33 child and 34 mental health nursing and 34 paramedic practice students). Methods: Stream A featured a seven station four-minute model with one interviewer at each station and in Stream B a six station model was employed. Cronbach’s alpha was used to assess MMI station internal consistency and Pearson’s moment correlation co-efficient to explore associations between participants’ admission MMI score and end of Year one clinical practice outcomes (OSCE and mentor grading). Results: Stream A: Significant correlations are reported between midwifery applicant’s MMI scores and end of Year One practice outcomes. A multivariate linear regression model demonstrated that MMI score significantly predicted end of Year One practice outcomes controlling for age and academic entry level: coefficients 0.195 (p = 0.002) and 0.116 (p = 0.002) for OSCE and mentor grading respectively. In Stream B no significant correlations were found between MMI score and practice outcomes measured by mentor grading. Internal consistency for each MMI station was ‘excellent’ with values ranging from 0.966–0.974 across Streams A and B. Conclusion: This novel, cross-discipline study shows that MMIs are reliable VBR tools which have predictive validity when a seven station model is used. These data are important given the current international use of different MMI models in healthcare student selection processes

Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation

The cyclic AMP-specific phosphodiesterase PDE8 has been shown to play a pivotal role in important processes such as steroidogenesis, T cell adhesion, regulation of heart beat and chemotaxis. However, no information exists on how the activity of this enzyme is regulated. We show that under elevated cAMP conditions, PKA acts to phosphorylate PDE8A on serine 359 and this action serves to enhance the activity of the enzyme. This is the first indication that PDE8 activity can be modulated by a kinase, and we propose that this mechanism forms a feedback loop that results in the restoration of basal cAMP levels. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserve

Interaction with receptor for activated C-kinase 1 (RACK1) sensitizes the phosphodiesterase PDE4D5 towards hydrolysis of cAMP and activation by protein kinase C

We have previously identified the PKC (protein kinase C)-anchoring protein RACK1 (receptor for activated C-kinase 1), as a specific binding partner for the cAMP-specific phosphodiesterase PDE4D5, suggesting a potential site for cross-talk between the PKC and cAMP signalling pathways. In the present study we found that elevation of intracellular cAMP, with the β2-adrenoceptor agonist isoproterenol (isoprenaline), led to activation of PDE4 enzymes in the particulate and soluble fractions of HEK (human embryonic kidney)-293 cells. In contrast activation of PDE4D5, with isoproterenol and the PKC activator PMA, was restricted to the particulate fraction, where it interacts with RACK1; however, RACK1 is dispensable for anchoring PDE4D5 to the particulate fraction. Kinetic studies demonstrated that RACK1 alters the conformation of particulate-associated PDE4D5 so that it more readily interacts with its substrate cAMP and with rolipram, a PDE4 inhibitor that specifically targets the active site of the enzyme. Interaction with RACK1 was also essential for PKC-dependent and ERK (extracellular-signal-regulated kinase)-independent phosphorylation (on Ser126), and activation of PDE4D5 in response to PMA and isoproterenol, both of which trigger the recruitment of PKCα to RACK1. Together these results reveal novel signalling cross-talk, whereby RACK1 mediates PKC-dependent activation of PDE4D5 in the particulate fraction of HEK-293 cells in response to elevations in intracellular cAMP

Rapid screening of environmental chemicals for estrogen receptor binding capacity.

Over the last few years, an increased awareness of endocrine disrupting chemicals (EDCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity in a wide range of environmental and industrial chemicals. While it is clear that in vivo methods will be required to identify adverse effects produced by these chemicals, in vitro assays can define particular mechanisms of action and have the potential to be employed as rapid and low-cost screens for use in large scale EDC screening programs. Traditional estrogen receptor (ER) binding assays are useful for characterizing a chemical's potential to be an estrogen-acting EDC, but they involve displacement of a radioactive ligand from crude receptor preparations at low temperatures. The usefulness of these assays for realistically determining the ER binding interactions of weakly estrogenic environmental and industrial compounds that have low aqueous solubility is unclear. In this report, we present a novel fluorescence polarization (FP) method that measures the capacity of a competitor chemical to displace a high affinity fluorescent ligand from purified, recombinant human ER-[alpha] at room temperature. The ER-[alpha] binding interactions generated for 15 natural and synthetic compounds were found to be similar to those determined with traditional receptor binding assays. We also discuss the potential to employ this FP technology to binding studies involving ER-ss and other receptors. Thus, the assay introduced in this study is a nonradioactive receptor binding method that shows promise as a high throughput screening method for large-scale testing of environmental and industrial chemicals for ER binding interactions

Voting power measurement: a story of misreinvention

In this account of the history of voting-power measurement, we confine ourselves to the concept of a priori voting power. We show how the concept was re-invented several times and how the circumstances in which it was reinvented led to conceptual confusion as to the true meaning of what is being measured. In particular, power-as-influence was conflated with value in the sense of transferable utility cooperative game theory (power as share in constant total payoff). Influence was treated, improperly, as though it were transferable utility, and hence an additive and distributive quantity. We provide examples of the resulting misunderstanding and mis-directed criticism

Quantum Monte Carlo Calculations of Pion Scattering from Li

We show that the neutron and proton transition densities predicted by recent quantum Monte Carlo calculations for A=6,7 nuclei are consistent with pion scattering from 6Li and 7Li at energies near the Delta resonance. This has provided a microscopic understanding of the enhancement factors for quadrople excitations, which were needed to describe pion inelastic scattering within the nuclear shell model of Cohen and Kurath.Comment: 10 pages, REVTeX, 3 postscript figures; added calculation of elastic and inelastic pion scattering from 6Li at multiple energie