721 research outputs found

    Testing goodwill: Conflict and co-operation in new product development networks

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    Network forms are often seen as models of organisational flexibility, promoting the building of trust and exchange of information between different business functions while offering both cost savings and reductions in the uncertainties usually associated with innovation. Both internal and external networks have been identified as key elements in the collaborative development of new products. The actual process of network building and ongoing network management is not well researched, although the existing literature highlights difficulties for organisations attempting to maintain active product development networks. This article examines the development and management of such a network in the defence industry and focuses on network building processes in terms of the interactions between the individuals involved. This network has endured and evolved over many years despite a series of conflicts. One of the key findings is that the effective functioning of the overall network is closely allied to established processes within the two participating firms

    Do Job Destruction Shocks Matter in the Theory of Unemployment?

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    The current DMP approach to labor markets presumes job destruction shocks are small. We relax that assumption and also allow un lled jobs, like unemployment, to evolve as a state variable. Calibrating an otherwise standard DMP framework, we identify a remarkable, (almost) perfect, fit of the empirical facts as reported in Shimer (2005, 2012). The results, how- ever, are also consistent with the insights of Davis and Haltiwanger (1992): that unemployment volatility is driven by large but infrequent job separation shocks. The approach not only provides an important synthesis of two litera- tures which, in other contexts, have appeared contradictory, it also identfies a more traditional view of the timing and progression of recessions

    Synthetic use of the primary kinetic isotope effect in hydrogen atom transfer: generation of α-aminoalkyl radicals.

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    addresses: School of Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, UKEX4 4QD. [email protected]: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2010 Royal Society of ChemistryThe extent to which deuterium can act as a protecting group to prevent unwanted 1,5-hydrogen atom transfer to aryl and vinyl radical intermediates was examined in the context of the generation of α-aminoalkyl radicals in a pyrrolidine ring. Intra- and intermolecular radical trapping following hydrogen atom transfer provides an illustration of the use of the primary kinetic isotope effect in directing the outcome of synthetic C-C bond-forming processes

    Can patient decision aids reduce decisional conflict in a de-escalation of breast radiotherapy clinical trial? The PRIMETIME Study Within a Trial implemented using a cluster stepped-wedge trial design

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    Background For patients with early breast cancer considered at very-low risk of local relapse, risks of radiotherapy may outweigh the benefits. Decisions regarding treatment omission can lead to patient uncertainty (decisional conflict), which may be lessened with patient decision aids (PDA). PRIMETIME (ISRCTN 41579286) is a UK-led biomarker-directed study evaluating omission of adjuvant radiotherapy in breast cancer; an embedded Study Within A Trial (SWAT) investigated whether PDA reduces decisional conflict using a cluster stepped-wedge trial design.Methods PDA diagrams and a video explaining risks and benefits of radiotherapy were developed in close collaboration between patient advocates and PRIMETIME trialists. The SWAT used a cluster stepped-wedge trial design, where each cluster represented the radiotherapy centre and referring peripheral centres. All clusters began in the standard information group (patient information and diagrams) and were randomised to cross-over to the enhanced information group (standard information plus video) at 2, 4 or 6 months. Primary endpoint was the decisional conflict scale (0-100, higher scores indicating greater conflict) which was assessed on an individual participant level. Multilevel mixed effects models used a random effect for cluster and a fixed effect for each step to adjust for calendar time and clustering. Robust standard errors were also adjusted for the clustering effect.Results Five hundred twenty-one evaluable questionnaires were returned from 809 eligible patients (64%) in 24 clusters between April 2018 and October 2019. Mean decisional conflict scores in the standard group (N = 184) were 10.88 (SD 11.82) and 8.99 (SD 11.82) in the enhanced group (N = 337), with no statistically significant difference [mean difference - 1.78, 95%CI - 3.82-0.25, p = 0.09]. Compliance with patient information and diagrams was high in both groups although in the enhanced group only 121/337 (36%) reported watching the video.Conclusion The low levels of decisional conflict in PRIMETIME are reassuring and may reflect the high-quality information provision, such that not everyone required the video. This reinforces the importance of working with patients as partners in clinical trials especially in the development of patient-centred information and decision aids

    Classification of fibroglandular tissue distribution in the breast based on radiotherapy planning CT

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    Accurate segmentation of breast tissues is required for a number of applications such as model based deformable registration in breast radiotherapy. The accuracy of breast tissue segmentation is affected by the spatial distribution (or pattern) of fibroglandular tissue (FT). The goal of this study was to develop and evaluate texture features, determined from planning computed tomography (CT) data, to classify the spatial distribution of FT in the breas

    {\phi}^4 Solitary Waves in a Parabolic Potential: Existence, Stability, and Collisional Dynamics

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    We explore a {\phi}^4 model with an added external parabolic potential term. This term dramatically alters the spectral properties of the system. We identify single and multiple kink solutions and examine their stability features; importantly, all of the stationary structures turn out to be unstable. We complement these with a dynamical study of the evolution of a single kink in the trap, as well as of the scattering of kink and anti-kink solutions of the model. We see that some of the key characteristics of kink-antikink collisions, such as the critical velocity and the multi-bounce windows, are sensitively dependent on the trap strength parameter, as well as the initial displacement of the kink and antikink

    Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing

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    Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)’s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance

    Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

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    INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years
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