High Performance Leadership: Narratives of identity and control in corporate leadership development and performance management

This article reviews the outcomes of a three year workshop series with senior leadership and management development managers from a range of public and private sector organisations. The aim of this enquiry was to explore the interface between performance management and leadership development systems and the extent to which they can complement one another to offer a coherent progression and performance framework. A number of competing and inter-related dynamics were uncovered that influence the extent to which performance management systems facilitate appropriate and desirable forms of behaviour in organisations and the extent to which these are supported and reinforced through leadership development. The most significant of these influences was seen to be one of identity and the impact that these systems can have on a sense of shared ‘social identity’ and purpose. By way of conclusion we argue that the narrative function of corporate leadership systems in expressing ‘who we are’ and ‘what we value’ is equally, if not more, important in determining their impact (positive or negative) than their corrective or developmental capacity per se

Stimulation of NSF ATPase activity during t-SNARE priming

AbstractN-Ethylmaleimide-sensitive factor (NSF) plays a key role in vesicular traffic by disassembling and priming SNARE proteins for their function in docking and fusion. We demonstrate that the ATPase activity of NSF is activated by α-soluble NSF attachment protein (α-SNAP) in a complex with syntaxin 1A. In addition, we show that a construct consisting of the H3 domain of syntaxin 1A (GST-synt(195–263), which does not support NSF disassembly in the presence of MgATP gave a larger stimulation. NSF ATPase activation was specific and did not occur using mutant α-SNAPs unable to bind GST-synt or with mutated C-termini. We suggest that activation of NSF ATPase activity in the SNARE complex may be essential to allow SNARE priming

The Difference that Makes the Difference - Final evaluation of the first place-based programmes for Systems Leadership: Local Vision

1.This report outlines findings from Phase 2 of the evaluation of Systems Leadership: Local Vision, conducted by Bristol Leadership Centre on behalf of the Systems Leadership Steering Group. It is the third in a series of reports capturing the learning and outcomes of the first cohort of Local Vision projects.2.In this report we focus on the outcomes and effects of Local Vision projects in different localities and consider how local context enables or constrains the potential for sustainable change. This analysis is based on case studies, interviews and secondary data.3.Overall, the findings suggest that Local Vision has had a positive impact within each of the areas investigated, complementing existing initiatives and catalysing change and engagement amongst partners and communities. 4.There is good evidence of Local Vision projects raising awareness of systems leadership amongst stakeholders in different localities – in particular in relation to thinking systemically, working collaboratively, engaging with service users, and fostering shared leadership.5.Likewise, there is good evidence that Local Vision has been regarded as a success in most localities, producing benefits and value for a diversity of stakeholders, such as influencing strategy, generating income and opportunities, engaging professionals, and improving services and client outcomes. 6.Whilst, in many cases it is still a little too early to determine the legacy and any lasting change arising from Local Vision, there is good evidence of its ability to catalyse change, influence new ways of working, and build commitment and momentum in relation to ‘wicked’ issues. 7.The case studies conducted during this phase of the evaluation enable the identification of a number of trends across projects that suggest some important ingredients of effective systems leadership interventions. These include start-up conditions (including the nature of the problem/challenge, level of intervention, prior experience of systems working, and imperative for change); local context (including alignment with other initiatives, project ownership, dedicated project support, and senior-level organisational and political engagement); process (including choice of Enabler, engagement with local communities, memorandum of understanding, King’s Fund learning network, and scale and timing of projects); and planning for sustainability (including project leadership, Enabler exit conditions, roll-out, and evaluating outcomes).8.Alongside the collection and analysis of evidence from Local Vision project partners and Enablers, the evaluation also collated and analysed a wide range of independent metrics on localities and the nature and scale of the ‘wicked’ issues that projects were tackling. Whilst these analyses did not reveal many insights into the Local Vision projects themselves, they do illuminate the challenges of benchmarking complex change interventions, and highlight the potential value of data as a leadership tool for galvanising action in complex and contested environments. 9.The report concludes with a summary of key outcomes and recommendations for future activity on Local Vision and related systems leadership initiatives. The evidence from this evaluation suggests that Local Vision can be regarded as a successful initiative that has succeeded in developing and embedding learning about systems leadership and change in the majority of localities where it has operated. As a place-based intervention, supported by skilled ‘Enablers’, Local Vision has successfully catalysed collaboration between multiple stakeholders to address shared challenges.10.The evaluation findings prove testament to the skill and tenacity of the Local Vision Enablers, project partners and the Leadership Centre (who coordinated and supported the initiative on behalf of the Systems Leadership Steering Group) in brokering relationships, facilitating difficult conversations and (re)connecting diverse communities to a shared sense of purpose. In most localities, there are now people committed to thinking systemically, working collaboratively, engaging with service users, and fostering shared leadership that will continue to have an impact for many years to come

Reframing, Realignment and Relationships - Interim evaluation of the first place-based programmes for Systems Leadership: Local Vision

In Autumn 2014 Bristol Leadership Centre at the University of the West of England was commissioned to undertake evaluation of the Local Vision programme.The evaluation is designed in two phases. This interim report sets out our findings for Phase 1, with a primary focus on identifying and exploring key criteria that may shape efficacy and impact. This will inform the developing evaluation framework, collective ‘sense making’ and deeper exploration of programme outcomes planned for Phase 2 of the evaluation, with a final report to be published in autumn 2015

A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits

We tested the hypothesis that genes encoded on the sex chromosomes play a direct role in sexual differentiation of brain and behavior. We used mice in which the testis-determining gene (Sry) was moved from the Y chromosome to an autosome (by deletion of Sry from the Y and subsequent insertion of an Sry transgene onto an autosome), so that the determination of testis development occurred independently of the complement of X or Y chromosomes. We compared XX and XY mice with ovaries (females) and XX and XY mice with testes (males). These comparisons allowed us to assess the effect of sex chromosome complement (XX vs XY) independent of gonadal status (testes vs ovaries) on sexually dimorphic neural and behavioral phenotypes. The phenotypes included measures of male copulatory behavior, social exploration behavior, and sexually dimorphic neuroanatomical structures in the septum, hypothalamus, and lumbar spinal cord. Most of the sexually dimorphic phenotypes correlated with the presence of ovaries or testes and therefore reflect the hormonal output of the gonads. We found, however, that both male and female mice with XY sex chromosomes were more masculine than XX mice in the density of vasopressin-immunoreactive fibers in the lateral septum. Moreover, two male groups differing only in the form of their Sry gene showed differences in behavior. The results show that sex chromosome genes contribute directly to the development of a sex difference in the brain

Reproducibility of in-vivo OCT measured three-dimensional human lamina cribrosa microarchitecture

Purpose: To determine the reproducibility of automated segmentation of the three-dimensional (3D) lamina cribrosa (LC) microarchitecture scanned in-vivo using optical coherence tomography (OCT). Methods: Thirty-nine eyes (8 healthy, 19 glaucoma suspects and 12 glaucoma) from 49 subjects were scanned twice using swept-source (SS-) OCT in a 3.5x3.5x3.64 mm (400x400x896 pixels) volume centered on the optic nerve head, with the focus readjusted after each scan. The LC was automatically segmented and analyzed for microarchitectural parameters, including pore diameter, pore diameter standard deviation (SD), pore aspect ratio, pore area, beam thickness, beam thickness SD, and beam thickness to pore diameter ratio. Reproducibility of the parameters was assessed by computing the imprecision of the parameters between the scans. Results: The automated segmentation demonstrated excellent reproducibility. All LC microarchitecture parameters had an imprecision of less or equal to 4.2%. There was little variability in imprecision with respect to diagnostic category, although the method tends to show higher imprecision amongst healthy subjects. Conclusion: The proposed automated segmentation of the LC demonstrated high reproducibility for 3D LC parameters. This segmentation analysis tool will be useful for in-vivo studies of the LC. © 2014 Wang et al

Viscoelastic material properties of the peripapillary sclera in normal and early-glaucoma monkey eyes

PURPOSE. To test the hypothesis that changes in the viscoelastic material properties of peripapillary sclera are present within monkey eyes at the onset of early experimental glaucoma detected by confocal scanning laser tomography (CSLT). METHODS. Short-term (3-9 weeks), moderate (Յ44 mm Hg) intraocular pressure (IOP) elevation was induced in one eye of each of eight male monkeys by lasering the trabecular meshwork. This procedure generated early experimental glaucoma, defined as the onset of CSLT-detected optic nerve head (ONH) surface change, in the treated eye. Scleral tensile specimens from the superior and inferior quadrants of the eight earlyglaucoma eyes were subjected to uniaxial stress relaxation and tensile tests to failure and the results compared with similar data obtained in a previous study of 12 normal (nonglaucomatous) eyes. Linear viscoelastic theory was used to characterize viscoelastic material property parameters for each specimen. Differences in each parameter due to quadrant and treatment were assessed by analysis of variance (ANOVA). RESULTS. Peripapillary sclera from the early-glaucoma eyes exhibited an equilibrium modulus (7.46 Ϯ 1.58 MPa) that was significantly greater than that measured in normal eyes (4.94 Ϯ 1.22 MPa; mean Ϯ 95% confidence interval, P Ͻ 0.01, ANOVA). Quadrant differences were not significant for the viscoelastic parameters within each treatment group. CONCLUSIONS. The long-term viscoelastic material properties of monkey peripapillary sclera are altered by exposure to moderate, short-term, chronic IOP elevations and these alterations are present at the onset of CSLT-detected glaucomatous damage to the ONH. Damage to and/or remodeling of the extracellular matrix of these tissues may underlie these changes in scleral material properties. (Invest Ophthalmol Vis Sci. 2005;46: 540 -546 1 The finite element method is a computer-based engineering technique that estimates the stresses (force/cross-sectional area) and strains (local deformation under those stresses) within a complex load-bearing structure. 2 The important aspects of a finite element model are the three-dimensional geometry and material properties of the load-bearing structure and the appropriate boundary and mechanical loading conditions. 2 Within such models of the monkey ONH, scleral material properties are needed to characterize accurately the important transition between the peripapillary sclera and the peripheral laminar beams. To characterize the material properties of peripapillary sclera, we constructed a controlled-environment testing apparatus capable of performing uniaxial biomechanical testing of soft tissues in tension. The overall response of a tissue to a load is the combination of instantaneous (elastic) and time-dependent (viscous) responses, which are governed by its viscoelastic material properties. All soft tissues are viscoelastic, and the characterization of the instantaneous and time-dependent aspects of these material properties is important in understanding a tissue's behavior as a load-bearing structure and its response to short-and long-term changes in the applied load. Accurate characterization of a tissue's material properties can lead to a broader understanding of the mechanisms that underlie tissue damage, as well as determine the resultant altered load-bearing behavior of a remodeled or healed tissue. In a previous report we performed quadrant-based uniaxial tensile testing of peripapillary sclera from normal rabbit and normal monkey eyes 3 and found no differences in the viscoelastic material properties of the peripapillary sclera by quadrant (superior, inferior, nasal, and temporal to the ONH) in either species. In addition, when normal rabbit and monkey sclera were compared with one another, peripapillary sclera from monkey eyes was stiffer and showed slower stress relaxation than sclera from rabbit eyes. The present study tests the hypothesis that changes in the viscoelastic material properties of monkey peripapillary sclera are present at the earliest detectable stage of glaucomatous damage to the ONH, defined as the onset of confocal scanning laser tomography (CSLT)-detected ONH surface change. MATERIALS AND METHODS Animals, Scleral Specimens, and Study Design All animals were treated in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. In the present study, a single scleral tensile specimen was generated from either the superior or inferior quadrant of eight eyes with experimental early glaucoma, yielding four early-glaucoma specimens for each quadrant. Each specimen underwent a multistage uniaxial tensile test. ViscoelasFrom th

Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis

The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and diseaserelated end points. Here we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy