Paper 1: Conceptualizing the transition from advanced to consultant practitioner: career promotion or significant life event?

Background The diversification of nursing and allied health profession (AHP) roles has seen unprecedented growth as organizations have sought to optimize limited health care resources. Within the UK health care system, the nonmedical consultant is viewed as the pinnacle of the clinical career ladder. Yet, nearly 15 years after their introduction, recruitment to these positions remains slow. Criticisms of nonmedical consultant practice include a lack of role clarity, a failure to work across the four domains of consultant practice, a lack of suitable applicants, and poor preparedness of new appointments. Although there is evidence exploring the nature and effectiveness of established consultant roles, little research addresses the development phase of aspiring consultants. Objectives To explore the transitional journey experienced by trainee consultant radiographers as they move from advanced to consultant practitioner within a locally devised consultant development programme. Design Longitudinal qualitative enquiry. Methods and Settings Five trainee consultant radiographers were recruited to a locally devised consultant practice development program within a single UK hospital trust. Semistructured interviews were undertaken at 1, 6, and 12 months with the trainees. Results A challenging journey was recounted involving five key emotional stages that occurred in a consistent and predictable order (ie, elation, denial, doubt, crisis, and recovery). The identified stages had close parallels with Hopson's Life Events model, suggesting that transition to consultant practice is a significant life event rather than a straightforward job promotion. Conclusions Current emphasis on the four domains of practice, although providing a clear framework for expected external role outcomes, overlooks the importance of the internal or subjective career development on the perceived success or failure of the role. Employers, educators, and professional bodies have a responsibility to facilitate aspirational consultants to explore and enhance their internal career development, offering more time to define themselves and their role with support to guide them through the transition journey

Endothelin-1 augments Na⁺/H⁺ exchange activity in murine pulmonary arterial smooth muscle cells via Rho kinase.

Excessive production of endothelin-1 (ET-1), a potent vasoconstrictor, occurs with several forms of pulmonary hypertension. In addition to modulating vasomotor tone, ET-1 can potentiate pulmonary arterial smooth muscle cell (PASMC) growth and migration, both of which contribute to the vascular remodeling that occurs during the development of pulmonary hypertension. It is well established that changes in cell proliferation and migration in PASMCs are associated with alkalinization of intracellular pH (pH(i)), typically due to activation of Na(+)/H(+) exchange (NHE). In the systemic vasculature, ET-1 increases pH(i), Na(+)/H(+) exchange activity and stimulates cell growth via a mechanism dependent on protein kinase C (PKC). These results, coupled with data describing elevated levels of ET-1 in hypertensive animals/humans, suggest that ET-1 may play an important role in modulating pH(i) and smooth muscle growth in the lung; however, the effect of ET-1 on basal pH(i) and NHE activity has yet to be examined in PASMCs. Thus, we used fluorescent microscopy in transiently (3-5 days) cultured rat PASMCs and the pH-sensitive dye, BCECF-AM, to measure changes in basal pH(i) and NHE activity induced by increasing concentrations of ET-1 (10(-10) to 10(-8) M). We found that application of exogenous ET-1 increased pH(i) and NHE activity in PASMCs and that the ET-1-induced augmentation of NHE was prevented in PASMCs pretreated with an inhibitor of Rho kinase, but not inhibitors of PKC. Moreover, direct activation of PKC had no effect on pH(i) or NHE activity in PASMCs. Our results indicate that ET-1 can modulate pH homeostasis in PASMCs via a signaling pathway that includes Rho kinase and that, in contrast to systemic vascular smooth muscle, activation of PKC does not appear to be an important regulator of PASMC pH(i)

Effect of PKC activation on intracellular pH (pH_i) and Na⁺/H⁺ exchanger (NHE) activity.

<p>Representative traces show pH_i measured during ammonium pulse in the <b>A)</b> absence and <b>B)</b> presence of PMA (1 μmol/L). <b>C and D)</b> Bar graphs show mean±SEM for <b>C)</b> the change (Δ) in baseline pH_i (n = 7) and <b>D)</b> NHE activity (n = 8) in response to PMA.</p

Effect of ROCK inhibition on intracellular pH (pH_i) and Na⁺/H⁺ exchanger (NHE) activity.

<p><b>A)</b> Bar graph showing mean±SEM values for basal pH_i measured in cells in the absence (n = 4) or presence (n = 4) of Y-27632 (10 μmol/L; 30 min). <b>B)</b> Bar graph shows mean±SEM values for the change (Δ) in baseline pH_i in response to ET-1 (10^-8 mol/L) in the absence (n = 5) and presence (n = 3) of Y-27632. <b>C)</b> Bar graph showing mean±SEM for NHE activity in cells challenged with ET-1 in the absence (n = 11) and presence (n = 5) of Y-27632. * indicates significant difference from control; †indicates significant difference from ET-1 alone.</p

Schematic illustrating the effect of endothelin-1 (ET-1) on intracellular pH (pH_i) in pulmonary arterial smooth muscle cells.

<p>ET-1 binds to surface receptors, leading to activation of Rho kinase (ROCK). ROCK activation in turn results in enhanced Na⁺/H⁺ exchanger (NHE) activity, increased H⁺ efflux and an alkaline shift in pH_i. </p

Effect of endothelin-1 (ET-1) on intracellular pH (pH_i) and Na⁺/H⁺ exchanger (NHE) activity.

<p><b>A)</b> Representative traces showing pH_i measured during the ammonium pulse protocol in control cells and cells treated with ET-1 (10^-8 M). <b>B and C)</b> Bar graphs showing mean±SEM values for <b>B)</b> the change (Δ) in baseline pH_i (n = 3-6) and <b>C)</b> NHE activity (n = 5-15) induced by different concentrations of ET-1. * indicates significant difference from control (0 nmol/L ET-1)</p

Effect of dimethyl amiloride (DMA; 1 μmol/L) on intracellular pH (pH_i) and Na⁺/H⁺ exchanger (NHE) activity.

<p><b>A and B)</b> Representative traces showing pH_i measured during the ammonium pulse protocol in cells treated with ET-1 (10^-8 M) in the <b>A)</b> absence and <b>B)</b> presence of DMA. <b>C and D)</b> Bar graphs showing mean±SEM values for <b>C)</b> the change (Δ) in baseline pH_i (n = 3-6) and <b>D)</b> NHE activity (n = 5-15) in control (Con) cells or in cells treated with DMA alone (n =  4 for pH_i and n = 6 for NHE activity) , ET-1 (10^-8 M; n =  5 for pH_i and n = 11 for NHE activity) and ET-1 + DMA (n = 6 for pH_i and n = 5 for NHE activity). * indicates significant difference from control; †indicates significant difference from ET-1 alone.</p

A new conceptualization of alexithymia in the general adult population : implications for research involving older adults

Objective: The purpose of this study is to test the validity of existing conceptualizations of the alexithymia concept, with particular reference to aging. Methods: Two hundred and forty-eight healthy adults completed measures of alexithymia and psychosocial functioning; younger and older adults (n=121) also completed a measure of emotional responsiveness. Results: Older adults engaged in less introspective thought traditionally thought to denote increased alexithymia. However, reduced introspection was associated with improved mental wellbeing, and, thus, could not be consumed as a deficit. Difficulty identifying and describing emotions did not differentiate older and younger adults, but were both associated with heightened depression, anxiety, and poor perceived quality of life. Conclusions: In clinical practice and research, the Toronto Alexithymia Scale (TAS) is almost exclusively used, with "total" score typically used to index alexithymia. As one of the subscales of the TAS measures reduced introspection, calculating total scores may not be appropriate and may particularly overestimate levels of alexithymia in older adulthood. (c) 2006 Elsevier Inc. All rights reserved

Intracellular cytokine production and cognition in healthy older adults

Elevated concentrations of the pro-inflammatory cytokines IL-1β and IL-6 have been associated with impaired cognitive performance. There are, however, few studies that have examined the relationship between cytokine production and specific aspects of cognition in healthy older individuals. Two-colour flow cytometry was used to determine intracellular cytokine production by activated monocytes, and neuropsychological tests were performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in 93 apparently healthy men and women aged 55–70 years. A series of hierarchical regression analyses was carried out to examine the contribution of IL-1β and IL-6 (% expression and production (antibody binding capacity (ABC))) to recognition, attention and working memory, after controlling for socio-demographic variables (age, sex and social class). IL-1β% expression and IL-6 production predicted aspects of working memory. Recognition memory was found to be sensitive to the affects of age and social class. The current study suggests that higher intracellular cytokine production by activated monocytes may be predictive of lower cognitive performance in working memory in healthy older individuals. These findings indicate that utilization of models for in vivo cytokine production upon immune challenge may be useful in studying specific aspects of memory affected during inflammatory responses, for example in individuals at risk for cognitive decline owing to age-related inflammatory disorders