86 research outputs found

    An activity theory perspective on strategy : a case study in a medium-sized manufacturing firm

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    This research contributes to theory by clarifying underlying activities behind productivity growth strategies from an in depth case study in a medium-sized manufacturing firm as well as providing suggestions to policy makers and practitioners who work on SME development in the UK and Europe

    Type-1 interferons contribute to oxygen glucose deprivation induced neuro-inflammation in BE(2)M17 human neuroblastoma cells

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    BACKGROUND: Hypoxic-ischaemic injuries such as stroke and traumatic brain injury exhibit features of a distinct neuro-inflammatory response in the hours and days post-injury. Microglial activation, elevated pro-inflammatory cytokines and macrophage infiltration contribute to core tissue damage and contribute to secondary injury within a region termed the penumbra. Type-1 interferons (IFNs) are a super-family of pleiotropic cytokines that regulate pro-inflammatory gene transcription via the classical Jak/Stat pathway; however their role in hypoxia-ischaemia and central nervous system neuro-inflammation remains unknown. Using an in vitro approach, this study investigated the role of type-1 IFN signalling in an inflammatory setting induced by oxygen glucose deprivation (OGD). METHODS: Human BE(2)M17 neuroblastoma cells or cells expressing a type-1 interferon-α receptor 1 (IFNAR1) shRNA or negative control shRNA knockdown construct were subjected to 4.5 h OGD and a time-course reperfusion period (0 to 24 h). Q-PCR was used to evaluate IFNα, IFNβ, IL-1β, IL-6 and TNF-α cytokine expression levels. Phosphorylation of signal transducers and activators of transcription (STAT)-1, STAT-3 and cleavage of caspase-3 was detected by western blot analysis. Post-OGD cellular viability was measured using a MTT assay. RESULTS: Elevated IFNα and IFNβ expression was detected during reperfusion post-OGD in parental M17 cells. This correlated with enhanced phosphorylation of STAT-1, a downstream type-1 IFN signalling mediator. Significantly, ablation of type-1 IFN signalling, through IFNAR1 knockdown, reduced IFNα, IFNβ, IL-6 and TNF-α expression in response to OGD. In addition, MTT assay confirmed the IFNAR1 knockdown cells were protected against OGD compared to negative control cells with reduced pro-apoptotic cleaved caspase-3 levels. CONCLUSIONS: This study confirms a role for type-1 IFN signalling in the neuro-inflammatory response following OGD in vitro and suggests its modulation through therapeutic blockade of IFNAR1 may be beneficial in reducing hypoxia-induced neuro-inflammation

    Editorial: From judge to jury: the potential for crowd reviewing

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    In this editorial, we introduce the four best papers selected from the IPSERA 2021 conference for this special issue of the Journal. We discuss how a double-blind crowd review (CR) process was used as an alternative to the traditional "two reviewer " double-blind peer review system. After a brief review of the literature and the existing debate around academic peer review, we introduce the main characteristics of CR. Next, at the core of our discussion, we report on the results of a pilot CR project that we conducted to review JPSM articles associated with the 2021 IPSERA Conference. We describe in detail the review process, and we illustrate the feedback received from reviewers and authors on the CR process, as well as our perspective as guest editors. Finally, we draw some conclusions and present recommendations for CR in the Purchasing and Supply Management (PSM) field. The CR pilot contributes to the wider debate around peer-reviewing by offering insights into the experience of different stakeholders and by highlighting the benefits and pitfalls of CR

    Demonstration of coherent emission from high-β\beta photonic crystal nanolasers at room temperature

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    We report on lasing at room temperature and at telecommunications wavelength from photonic crystal nanocavities based on InAsP/InP quantum dots. Such laser cavities with a small modal volume and high quality factor display a high spontaneous emission coupling factor beta. Lasing is confirmed by measuring the second order autocorrelation function. A smooth transition from chaotic to coherent emission is observed, and coherent emission is obtained at 8 times the threshold power

    Towards a mixed method approach for the multidisciplinary investigation of management processes

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    This paper presents the development of a mixed methods approach by a multidisciplinary group of academics to understand and so model management processes with a view to enabling informed management decision making. Considering management processes as one of three categories of business processes (CIMOSA Standards Committee, 1989), the literature in this area is reviewed to identify current management modelling techniques. The researchers conclude that these do not adequately address both the 'hard' and 'soft' characteristics of management processes as well as the methodological viewpoints of the group. The development of a mixed method approach designed to address these issues is presented, along with an explanation of its application in practice. The paper concludes with a critical evaluation of the method and outlines future developmental work planned by the research group. The value in this approach is that it informs both academia and the business community by proposing a transparent and repeatable method of understanding the subjective topics of management practices and processes that is grounded in both a priori theory and practical data

    Hard Two-Photon Contribution to Elastic Lepton-Proton Scattering: Determined by the OLYMPUS Experiment

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    The OLYMPUS collaboration reports on a precision measurement of the positron-proton to electron-proton elastic cross section ratio, R2γR_{2\gamma}, a direct measure of the contribution of hard two-photon exchange to the elastic cross section. In the OLYMPUS measurement, 2.01~GeV electron and positron beams were directed through a hydrogen gas target internal to the DORIS storage ring at DESY. A toroidal magnetic spectrometer instrumented with drift chambers and time-of-flight scintillators detected elastically scattered leptons in coincidence with recoiling protons over a scattering angle range of 20°\approx 20\degree to 80°80\degree. The relative luminosity between the two beam species was monitored using tracking telescopes of interleaved GEM and MWPC detectors at 12°12\degree, as well as symmetric M{\o}ller/Bhabha calorimeters at 1.29°1.29\degree. A total integrated luminosity of 4.5~fb1^{-1} was collected. In the extraction of R2γR_{2\gamma}, radiative effects were taken into account using a Monte Carlo generator to simulate the convolutions of internal bremsstrahlung with experiment-specific conditions such as detector acceptance and reconstruction efficiency. The resulting values of R2γR_{2\gamma}, presented here for a wide range of virtual photon polarization 0.456<ϵ<0.9780.456<\epsilon<0.978, are smaller than some hadronic two-photon exchange calculations predict, but are in reasonable agreement with a subtracted dispersion model and a phenomenological fit to the form factor data.Comment: 5 pages, 3 figures, 2 table

    Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

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    Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

    Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

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    Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

    Order from Chaos: A Meta-Analysis of Supply Chain Complexity and Firm Performance

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    Increased globalization, varying customer requirements, extended product lines, uncertainty regarding supplier performance, and myriad related factors make supply chains utterly complex. While previous research indicates that supply chain complexity plays an important role in explaining performance outcomes, the accumulating evidence is ambiguous. Thus, a finer-grained analysis is required. By meta-analyzing 27,668 observations across 102 independent samples from 123 empirical studies, we examine the link between supply chain complexity and firm performance. While the preponderance of evidence from previous studies identifies supply chain complexity as detrimental to firm performance, our results illustrate that although supply chain complexity has a negative effect on operational performance, it has a positive effect on innovation performance and financial performance. Furthermore, we also distinguish among different levels of supply chain (i.e., upstream, downstream, and internal) and observe nuanced findings. Finally, our findings also reveal moderating effects of construct operationalization and study design characteristics. We discuss implications for theory and practice and provide avenues for future research

    An end-to-end process view of strategy management : a research framework

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    This paper discusses an end to end process view of strategy management. It was presented at the 27th international annual strategic management society conference
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