What is Strategic Competence and Does it Matter? Exposition of the Concept and a Research Agenda

Drawing on a range of theoretical and empirical insights from strategic management and the cognitive and organizational sciences, we argue that strategic competence constitutes the ability of organizations and the individuals who operate within them to work within their cognitive limitations in such a way that they are able to maintain an appropriate level of responsiveness to the contingencies confronting them. Using the language of the resource based view of the firm, we argue that this meta-level competence represents a confluence of individual and organizational characteristics, suitably configured to enable the detection of those weak signals indicative of the need for change and to act accordingly, thereby minimising the dangers of cognitive bias and cognitive inertia. In an era of unprecedented informational burdens and instability, we argue that this competence is central to the longer-term survival and well being of the organization. We conclude with a consideration of the major scientific challenges that lie ahead, if the ideas contained within this paper are to be validated

Progression from ocular hypertension to visual field loss in the English hospital eye service

Background There are more than one million National Health Service visits in England and Wales each year for patients with glaucoma or ocular hypertension (OHT). With the ageing population and an increase in optometric testing, the economic burden of glaucoma-related visits is predicted to increase. We examined the conversion rates of OHT to primary open-angle glaucoma (POAG) in England and assessed factors associated with risk of conversion. Methods Electronic medical records of 45 309 patients from five regionally different glaucoma clinics in England were retrospectively examined. Conversion to POAG from OHT was defined by deterioration in visual field (two consecutive tests classified as stage 1 or worse as per the glaucoma staging system 2). Cox proportional hazards models were used to examine factors (age, sex, treatment status and baseline intraocular pressure (IOP)) associated with conversion. Results The cumulative risk of conversion to POAG was 17.5% (95% CI 15.4% to 19.6%) at 5 years. Older age (HR 1.35 per decade, 95% CI 1.22 to 1.50, p<0.001) was associated with a higher risk of conversion. IOP-lowering therapy (HR 0.45, 95% CI 0.35 to 0.57, p<0.001) was associated with a lower risk of conversion. Predicted 5-year conversion rates for treated and untreated groups were 14.0% and 26.9%, respectively. Conclusion Less than one-fifth of OHT patients managed in glaucoma clinics in the UK converted to POAG over a 5-year period, suggesting many patients may require less intensive follow-up. Our study provides real-world evidence for the efficacy of current management (including IOP-lowering treatment) at reducing risk of conversion

Auditing service delivery in glaucoma clinics using visual field records: A feasibility study

© 2019 Author(s). Objective This study aimed to demonstrate that large-scale visual field (VF) data can be extracted from electronic medical records (EMRs) and to assess the feasibility of calculating metrics from these data that could be used to audit aspects of service delivery of glaucoma care. Method and analysis Humphrey visual field analyser (HFA) data were extracted from Medisoft EMRs from five regionally different clinics in England in November 2015, resulting in 602 439 records from 73 994 people. Target patients were defined as people in glaucoma clinics with measurable and sustained VF loss in at least one eye (HFA mean deviation (MD) outside normal limits ≥2 VFs). Metrics for VF reliability, stage of VF loss at presentation, speed of MD loss, predicted loss of sight years (bilateral VF impairment) and frequency of VFs were calculated. Results One-third of people (34.8%) in the EMRs had measurable and repeatable VF loss and were subject to analyses (n=25 760 patients). Median (IQR) age and presenting MD in these patients were 71 (61, 78) years and -6 (-10, -4) dB, respectively. In 19 264 patients with >4 years follow-up, median (IQR) MD loss was -0.2 (-0.8, 0.3) dB/year and median (IQR) intervals between VF examinations was 11 (8, 16) months. Metrics predicting loss of sight years and reliability of examinations varied between centres (p<0.001). Conclusion This study illustrates the feasibility of assessing aspects of health service delivery in glaucoma clinics through analysis of VF databases. Proposed metrics could be useful for blindness prevention from glaucoma in secondary care centres

Direct transition to high-dimensional chaos through a global bifurcation

In the present work we report on a genuine route by which a high-dimensional (with d>4) chaotic attractor is created directly, i.e., without a low-dimensional chaotic attractor as an intermediate step. The high-dimensional chaotic set is created in a heteroclinic global bifurcation that yields an infinite number of unstable tori.The mechanism is illustrated using a system constructed by coupling three Lorenz oscillators. So, the route presented here can be considered a prototype for high-dimensional chaotic behavior just as the Lorenz model is for low-dimensional chaos.Comment: 7 page

Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits

Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis (TB), and is also used as an immunotherapy for bladder cancer and other malignancies due to its immunostimulatory properties. Mycobacteria spp., however, are well known for their numerous immune evasion mechanisms that limit the true potential of their therapeutic use. One such major mechanism is the induction of programmed death ligand-1 (PD-L1), which mitigates adaptive immune responses. Here, we sought to unravel the molecular pathways behind PD-L1 up-regulation on antigen-presenting cells (APCs) by BCG. We found that infection of APCs with BCG induced PD-L1 up-regulation, but that this did not depend on direct infection, suggesting a soluble mediator for this effect. BCG induced potent quantities of IL-6 and IL-10, and the downstream transcription factor STAT3 was hyper-phosphorylated. Intracellular analyses revealed that levels of PD-L1 molecules were associated with the STAT3 phosphorylation state, suggesting a causal link. Neutralisation of the IL-6 or IL-10 cytokine receptors dampened STAT3 phosphorylation and BCG-mediated up-regulation of PD-L1 on APCs. Pharmacological inhibition of STAT3 achieved the same effect, confirming an autocrine-paracrine cytokine loop as a mechanism for BCG-mediated up-regulation of PD-L1. Finally, an in vivo immunisation model showed that BCG vaccination under PD-L1 blockade could enhance antigen-specific memory CD4 T-cell responses. These novel findings could lead to refinement of BCG as both a vaccine for infectious disease and as a cancer immunotherapy

Analysis of the shearing instability in nonlinear convection and magnetoconvection

Numerical experiments on two-dimensional convection with or without a vertical magnetic field reveal a bewildering variety of periodic and aperiodic oscillations. Steady rolls can develop a shearing instability, in which rolls turning over in one direction grow at the expense of rolls turning over in the other, resulting in a net shear across the layer. As the temperature difference across the fluid is increased, two-dimensional pulsating waves occur, in which the direction of shear alternates. We analyse the nonlinear dynamics of this behaviour by first constructing appropriate low-order sets of ordinary differential equations, which show the same behaviour, and then analysing the global bifurcations that lead to these oscillations by constructing one-dimensional return maps. We compare the behaviour of the partial differential equations, the models and the maps in systematic two-parameter studies of both the magnetic and the non-magnetic cases, emphasising how the symmetries of periodic solutions change as a result of global bifurcations. Much of the interesting behaviour is associated with a discontinuous change in the leading direction of a fixed point at a global bifurcation; this change occurs when the magnetic field is introduced

Formation classification based on the well logs data with the use of machine learning

Plant-derived pharmaceuticals are poised to become the next major commercial development in biotechnology. The advantages they offer in terms of production scale and economy, product safety, ease of storage and distribution cannot be matched by any current commercial system; they also provide the most promising opportunity to supply low-cost drugs and vaccines to the developing world. However, despite the promised benefits, the commercialization of plant-derived pharmaceutical products is overshadowed by the uncertain regulatory terrain, particularly with regard to the adaptation of good manufacturing practice regulations to field-grown plants. The success of such products also depends on careful negotiation of the intellectual property landscape, particularly the achievement of freedom-to-operate licenses for use in developing countries