SME productivity stakeholders: Getting in the right orbit

Successive governments have developed strategies and initiatives over the last two decades to help SME’s increase productivity often through government funded quasi-agencies, the latest of these new industrial strategy document, The research aim of this paper was to explore from the SME perspective who they might consider are key stakeholders or agents for their business in terms of helping increase productivity, and what support these stakeholders might offer. The study uses the LEGO serious play methodology and narrative analysis to develop a stakeholder ‘orbital map’ which shows a small ‘depth of field’ of ‘close’ stakeholders, and the complexity of some of the resulting relationships, and the implications for policy makers

Geometric quantum computation with NMR

The experimental realisation of the basic constituents of quantum information processing devices, namely fault-tolerant quantum logic gates, requires conditional quantum dynamics, in which one subsystem undergoes a coherent evolution that depends on the quantum state of another subsystem. In particular, the subsystem may acquire a conditional phase shift. Here we consider a novel scenario in which this phase is of geometric rather than dynamical origin. As the conditional geometric (Berry) phase depends only on the geometry of the path executed it is resilient to certain types of errors, and offers the potential of an intrinsically fault-tolerant way of performing quantum gates. Nuclear Magnetic Resonance (NMR) has already been used to demonstrate both simple quantum information processing and Berry's phase. Here we report an NMR experiment which implements a conditional Berry phase, and thus a controlled phase shift gate. This constitutes the first elementary geometric quantum computation.Comment: Minor additions at request of referees. 4 pages revtex including 2 figures (1 eps). Nature in pres

Developing SME performance management practices: interventions for improving productivity

Purpose The paper is a proof of concept (PoC) intervention study aimed for developing performance management (PM) practices in manufacturing small and medium-sized enterprises (SMEs) with the longer-term aim enabling the SMEs to improve their productivity. The intervention was designed and deployed by a collaborative quartet of academics, management consultants, accountancy firm and a commercial bank manager. Design/methodology/approach The paper firstly musters a set of initialising PM practices aligned to productivity improvement. These are utilised to design a knowledge transfer intervention for deployment with a set of manufacturing SMEs incorporating some associated productivity tools. The evaluation of the intervention utilised a case study approach founded on a logic model of the intervention to assess the development of the PM practices. Findings The intervention contributed to a partial development of the mustered practices and the productivity diagnostic based on the multi-factor productivity (MFP) abstraction and a data extraction protocol had the strongest impact. The study revealed the importance of the three interlaced factors: Depth of engagement, feedback opportunities and the intervention gradient (the increase of independent action from the participating SME's and the diminishment of the external intervention effort). Research limitations/implications The case study is based on a limited number of individual SME's, and within just the manufacturing sector. Practical implications SME businesses will require a more sustained programme of interventions than this pilot to develop PM capability, and depth of engagement within the SME is critical. Professional stakeholders can be utilised in recruitment of firms for intervention programmes. Business can start developing PM capability prior to PMS implementation using the tools from this programme. Originality/value The productivity diagnostic tool, based on a synthesis of MFP and the performance pyramid, an array of potential initialising practices for PM capability and discovery of potential mechanisms for PM practice development

Development of a Kaizen series model: abducting a blend of participatory formats to enhance the development of process improvement practices

The paper utilises a form of Action Research, known as the ‘Constructive Research Approach’ (CRA), to explore how project teams could engender the development of process improvement (PI) routines in a higher education context. The methodology of Mediated Discourse Analysis (MDA), an ethnographic approach to researching practice, is used to trace the development of PI routines over time. The findings showed that process owners and actors who were engaged because of ‘power’ of an initial pre-project Kaizen event, then became more passive participants in the ensuing traditional improvement project, with reduced performances of the PI routines. The main contrition stemming from the work was the abduction of a hybrid model of participatory engagement, that of a ‘Kaizen series’. This extended series of events affords the development of two key routines, ‘the working with a process map’ and the process analysis routine, by increasing opportunity for actors to perform these routines both within and between events, and by balancing the facilitation and empowerment routines. In addition, the Kaizen series is not dependent on any individual PI methodology. The resulting Kaizen series offers PI practitioners an opportunity to blend the best aspects of two different modes of engagement, Kaizen events and project improvement teams

Historical database cohort study addressing the clinical patterns prior to idiopathic pulmonary fibrosis (IPF) diagnosis in UK primary care

OBJECTIVE: To explore the clinical pathways, including signs and symptoms, and symptom progression patterns preceding idiopathic pulmonary fibrosis (IPF) diagnosis. DESIGN AND SETTING: A historical cohort study was conducted using primary care patient records from the Optimum Patient Care Research Database. PARTICIPANTS: Patients included were at least 30 years, had IPF diagnosis, identified via clinical-coding and free-text records and had a consultation with a chest specialist prior to IPF diagnosis. OUTCOME MEASURES: The signs and symptoms in the year prior to IPF diagnosis from clinical codes and free-text in primary care electronic records included: cough, dyspnoea, dry cough, weight loss, fatigue/malaise, loss of appetite, crackles and clubbed fingers. The time course of presentations of clinical features and investigations in the years prior to IPF diagnosis were mapped. RESULTS: Within 462 patients identified, the majority (77.9%) had a respiratory consultation within 365 days prior to the chest specialist visit preceding the IPF diagnosis recorded in their primary care records. The most common symptoms recorded in the 1 year prior to IPF diagnosis were dyspnoea (48.7%) and cough (40.9%); other signs and symptoms were rarely recorded (<5%). The majority of patients with cough (58.0%) and dyspnoea (55.0%) in the 1 year before IPF diagnosis had multiple recordings of the respective symptoms. Both cough and dyspnoea were recorded in 23.4% of patients in the year prior to diagnosis. Consultation rates for cough, dyspnoea and both, but not other signs or symptoms, began to increase 4 to 5 years prior diagnosis, with the sharpest increase in the last year. Cough and dyspnoea were often preceded by a reduction in measured weight over 5 years leading to IPF diagnosis. CONCLUSION: Prolonged cough and/or progressive dyspnoea, especially if accompanied with weight loss, should signal for a referral to specialist assessment at the earliest opportunity

Discovery and Characterization of a Cryptic Secondary Binding Site in the Molecular Chaperone HSP70.

Heat Shock Protein 70s (HSP70s) are key molecular chaperones that are overexpressed in many cancers and often associated with metastasis and poor prognosis. It has proven difficult to develop ATP-competitive, drug-like small molecule inhibitors of HSP70s due to the flexible and hydrophilic nature of the HSP70 ATP-binding site and its high affinity for endogenous nucleotides. The aim of this study was to explore the potential for the inhibition of HSP70 through alternative binding sites using fragment-based approaches. A surface plasmon resonance (SPR) fragment screen designed to detect secondary binding sites in HSP70 led to the identification by X-ray crystallography of a cryptic binding site in the nucleotide-binding domain (NBD) of HSP70 adjacent to the ATP-binding site. Fragment binding was confirmed and characterized as ATP-competitive using SPR and ligand-observed NMR methods. Molecular dynamics simulations were applied to understand the interactions with the protein upon ligand binding, and local secondary structure changes consistent with interconversion between the observed crystal structures with and without the cryptic pocket were detected. A virtual high-throughput screen (vHTS) against the cryptic pocket was conducted, and five compounds with diverse chemical scaffolds were confirmed to bind to HSP70 with micromolar affinity by SPR. These results identified and characterized a new targetable site on HSP70. While targeting HSP70 remains challenging, the new site may provide opportunities to develop allosteric ATP-competitive inhibitors with differentiated physicochemical properties from current series

Adenomyoepithelial tumours and myoepithelial carcinomas of the breast – a spectrum of monophasic and biphasic tumours dominated by immature myoepithelial cells

BACKGROUND: Adenomyoepithelial tumours and myoepithelial carcinomas of the breast are primarily defined by the presence of neoplastic cells with a myoepithelial immunophenotype. Current classification schemes are based on purely descriptive features and an assessment of individual prognosis is still problematic. METHODS: A series of 27 adenomyoepithelial tumours of the breast was analysed immunohistochemically with antibodies directed against various cytokeratins, p63, smooth muscle alpha-actin (SMA) and vimentin. Additionally, double immunofluorescence and comparative genomic hybridisation (CGH) was performed. RESULTS: Immunohistochemically, all the tumours showed a constant expression of high molecular weight cytokeratins (Ck) Ck5 and Ck14, p63, SMA and vimentin. With exception of one case diagnosed as myoepithelial carcinoma, all tested tumours expressed low molecular weight cytokeratin Ck18 in variable proportions of cells. Even in monophasic tumours lacking obvious glandular differentiation in conventional staining, a number of neoplastic cells still expressed those cytokeratins. Double immunofluorescence revealed tumour cells exclusively staining for Ck5/Ck14 in the presence of other cell populations that co-expressed high molecular weight Ck5/Ck14 as well as either low molecular weight Ck8/18 or SMA. Based on morphology, we assigned the series to three categories, benign, borderline and malignant. This classification was supported by a stepwise increase in cytogenetic alterations on CGH. CONCLUSION: Adenomyoepithelial tumours comprise a spectrum of neoplasms consisting of an admixture of glandular and myoepithelial differentiation patterns. As a key component SMA-positive cells co-expressing cytokeratins could be identified. Although categorisation of adenomyoepithelial tumours in benign, borderline and malignant was supported by results of CGH, any assessment of prognosis requires to be firmly based on morphological grounds. At present it is not yet clear, if and to what extent proposed Ck5-positive progenitor cells contribute to the immunohistochemical and morphological heterogeneity of these neoplasms of the breast