Network diversity, distance and economic impact in a cluster: visualising linkages and assessing network capital

Purpose – Effective policy to support business ecosystems should build on evidence-based analyses of firm level activities and outcomes. This paper aims to contribute to this requirement and makes three contributions. The first contribution is to extend the application of the network capital concept to a variety of eight distinct linkage categories (e.g. suppliers, customers and business support agencies) that support networking and clustering, in both activity and impact terms. The second contribution is outlining a novel method of network visualisation (V-LINC) based on the collection of primary and qualitative data. The third contribution is in applying the method to one cluster, information and communications technologies. Design/methodology/approach – Qualitative research on the nature and extent of organisational network linkages was undertaken. Structured interviews with a set of focal firms followed a tailored design approach. The concept of network capital was extended and applied to the cluster context by measuring network inputs and output (i.e. investments and impact). The approach was operationalised via a novel impact measurement approach, denoted as V-LINC, an acronym for visualising linkages in networks and clusters. Findings – The authors develop a business impact framework exploiting novel linkage visualisations and qualitative data from firms in a cluster in one city region across eight linkage types to capture distinct network capital elements. Organisational inputs into network development, measured as investment and involvement indicators and organisational outcomes from those networks, measured as importance and intensity indicators, are used to assess network performance. A comprehensive, systematic and robust analysis of network elements and performance is possible. Distance is found to interact differently across linkage types. Targeted recommendations may be made from the analysis of local or regional business ecosystems in light of measured business impacts of linkages. Research limitations/implications – Due to the resource-intensive nature of data collection, the current study engages a limited sample of firms and interviewees. Applications of this approach in other contexts will permit further research into its usefulness in evaluating business impacts generated through networking activities. Originality/value – The method introduced here (V-LINC) offers a novel means to include both geography network theory into an understanding of knowledge relationships and networks within clusters. Accounting for both distance and linkage type reveals which categories of intra-regional and extra-regional linkages generate the greatest impact, given their frequency. The approach adds to available cluster visualisation and analysis approaches through identifying patterns of disaggregated knowledge flows and their impacts, with application to evaluation demands of policy

Influences on Decision-Making Regarding Antipsychotic Prescribing in Nursing Home Residents With Dementia: A Systematic Review and Synthesis of Qualitative Evidence.

BACKGROUND: Antipsychotic prescribing is prevalent in nursing homes for the management of behavioral and psychological symptoms of dementia (BPSD), despite the known risks and limited effectiveness. Many studies have attempted to understand this continuing phenomenon, using qualitative research methods, and have generated varied and sometimes conflicting findings. To date, the totality of this qualitative evidence has not been systematically collated and synthesized. AIMS: To synthesize the findings from individual qualitative studies on decision-making and prescribing behaviors for antipsychotics in nursing home residents with dementia, with a view to informing intervention development and quality improvement in this field. METHODS: A systematic review and synthesis of qualitative evidence was conducted (PROSPERO protocol registration CRD42015029141). Six electronic databases were searched systematically from inception through July 2016 and supplemented by citation, reference, and gray literature searching. Studies were included if they used qualitative methods for both data collection and analysis, and explored antipsychotic prescribing in nursing homes for the purpose of managing BPSD. The Critical Appraisal Skills Program assessment tool was used for quality appraisal. A meta-ethnography was conducted to synthesize included studies. The Confidence in the Evidence from Reviews of Qualitative research approach was used to assess the confidence in individual review findings. All stages were conducted by at least 2 independent reviewers. RESULTS: Of 1534 unique records identified, 18 met the inclusion criteria. Five key concepts emerged as influencing decision-making: organizational capacity; individual professional capability; communication and collaboration; attitudes; regulations and guidelines. A "line of argument" was synthesized and a conceptual model constructed, comparing this decision-making process to a dysfunctional negative feedback loop. Our synthesis indicates that when all stakeholders come together to communicate and collaborate as equal and empowered partners, this can result in a successful reduction in inappropriate antipsychotic prescribing. CONCLUSIONS: Antipsychotic prescribing in nursing home residents with dementia occurs in a complex environment involving the interplay of various stakeholders, the nursing home organization, and external influences. To improve the quality of antipsychotic prescribing in this cohort, a more holistic approach to BPSD management is required. Although we have found the issue of antipsychotic prescribing has been extensively explored using qualitative methods, there remains a need for research focusing on how best to change the prescribing behaviors identified

Attenuated CSF-1R signalling drives cerebrovascular pathology

Cerebrovascular pathologies occur in up to 80% of cases of Alzheimer's disease; however, the underlying mechanisms that lead to perivascular pathology and accompanying blood-brain barrier (BBB) disruption are still not fully understood. We have identified previously unreported mutations in colony stimulating factor-1 receptor (CSF-1R) in an ultra-rare autosomal dominant condition termed adult-onset leucoencephalopathy with axonal spheroids and pigmented glia (ALSP). Cerebrovascular pathologies such as cerebral amyloid angiopathy (CAA) and perivascular p-Tau were some of the primary neuropathological features of this condition. We have identified two families with different dominant acting alleles with variants located in the kinase region of the CSF-1R gene, which confer a lack of kinase activity and signalling. The protein product of this gene acts as the receptor for 2 cognate ligands, namely colony stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). Here, we show that depletion in CSF-1R signalling induces BBB disruption and decreases the phagocytic capacity of peripheral macrophages but not microglia. CSF-1R signalling appears to be critical for macrophage and microglial activation, and macrophage localisation to amyloid appears reduced following the induction of Csf-1r heterozygosity in macrophages. Finally, we show that endothelial/microglial crosstalk and concomitant attenuation of CSF-1R signalling causes re-modelling of BBB-associated tight junctions and suggest that regulating BBB integrity and systemic macrophage recruitment to the brain may be therapeutically relevant in ALSP and other Alzheimer's-like dementias

A WORKFLOW-ORIENTED APPROACH TO PROPAGATION MODELS IN HELIOPHYSICS

The Sun is responsible for the eruption of billions of tons of plasma andthe generation of near light-speed particles that propagate throughout the solarsystem and beyond. If directed towards Earth, these events can be damaging toour tecnological infrastructure. Hence there is an effort to understand the causeof the eruptive events and how they propagate from Sun to Earth. However, thephysics governing their propagation is not well understood, so there is a need todevelop a theoretical description of their propagation, known as a PropagationModel, in order to predict when they may impact Earth. It is often difficultto define a single propagation model that correctly describes the physics ofsolar eruptive events, and even more difficult to implement models capable ofcatering for all these complexities and to validate them using real observational data.In this paper, we envisage that workflows offer both a theoretical andpractical framerwork for a novel approach to propagation models. We definea mathematical framework that aims at encompassing the different modalitieswith which workflows can be used, and provide a set of generic building blockswritten in the TAVERNA workflow language that users can use to build theirown propagation models. Finally we test both the theoretical model and thecomposite building blocks of the workflow with a real Science Use Case that wasdiscussed during the 4th CDAW (Coordinated Data Analysis Workshop) eventheld by the HELIO project. We show that generic workflow building blocks canbe used to construct a propagation model that succesfully describes the transitof solar eruptive events toward Earth and predict a correct Earth-impact tim

Characterization and adaptation of Caldicellulosiruptor strains to higher sugar concentrations, targeting enhanced hydrogen production from lignocellulosic hydrolysates

Abstract Background The members of the genus Caldicellulosiruptor have the potential for future integration into a biorefinery system due to their capacity to generate hydrogen close to the theoretical limit of 4 mol H2/mol hexose, use a wide range of sugars and can grow on numerous lignocellulose hydrolysates. However, members of this genus are unable to survive in high sugar concentrations, limiting their ability to grow on more concentrated hydrolysates, thus impeding their industrial applicability. In this study five members of this genus, C. owensensis, C. kronotskyensis, C. bescii, C. acetigenus and C. kristjanssonii, were developed to tolerate higher sugar concentrations through an adaptive laboratory evolution (ALE) process. The developed mixed population C. owensensis CO80 was further studied and accompanied by the development of a kinetic model based on Monod kinetics to quantitatively compare it with the parental strain. Results Mixed populations of Caldicellulosiruptor tolerant to higher glucose concentrations were obtained with C. owensensis adapted to grow up to 80 g/L glucose; other strains in particular C. kristjanssonii demonstrated a greater restriction to adaptation. The C. owensensis CO80 mixed population was further studied and demonstrated the ability to grow in glucose concentrations up to 80 g/L glucose, but with reduced volumetric hydrogen productivities ( $$Q_{{{\text{H}}_{2} }}$$ Q H 2 ) and incomplete sugar conversion at elevated glucose concentrations. In addition, the carbon yield decreased with elevated concentrations of glucose. The ability of the mixed population C. owensensis CO80 to grow in high glucose concentrations was further described with a kinetic growth model, which revealed that the critical sugar concentration of the cells increased fourfold when cultivated at higher concentrations. When co-cultured with the adapted C. saccharolyticus G5 mixed culture at a hydraulic retention time (HRT) of 20 h, C. owensensis constituted only 0.09–1.58% of the population in suspension. Conclusions The adaptation of members of the Caldicellulosiruptor genus to higher sugar concentrations established that the ability to develop improved strains via ALE is species dependent, with C. owensensis adapted to grow on 80 g/L, whereas C. kristjanssonii could only be adapted to 30 g/L glucose. Although C. owensensis CO80 was adapted to a higher sugar concentration, this mixed population demonstrated reduced $$Q_{{{\text{H}}_{2} }}$$ Q H 2 with elevated glucose concentrations. This would indicate that while ALE permits adaptation to elevated sugar concentrations, this approach does not result in improved fermentation performances at these higher sugar concentrations. Moreover, the observation that planktonic mixed culture of CO80 was outcompeted by an adapted C. saccharolyticus, when co-cultivated in continuous mode, indicates that the robustness of CO80 mixed culture should be improved for industrial application

The Hydroxylase Inhibitor Dimethyloxallyl Glycine Attenuates Endotoxic Shock Via Alternative Activation of Macrophages and IL-10 Production by B1 Cells

Localized tissue hypoxia is a feature of infection and inflammation, resulting in the upregulation of the transcription factors HIF-1α and NF-κB via inhibition of oxygen sensing hydroxylase enzymes. Previous studies have demonstrated a beneficial role for the hydroxylase inhibitor dimethyloxallyl glycine (DMOG) in inflammatory conditions, including experimental colitis, by regulating the activity of HIF-1 and NF-κB. We have demonstrated in vivo that pre-treatment with DMOG attenuates systemic LPS-induced activation of the NF-κB pathway. Furthermore, mice treated with DMOG had significantly increased survival in LPS-induced shock. Conversely, in models of polymicrobial sepsis, DMOG exacerbates disease severity. DMOG treatment of mice promotes M2 polarization in macrophages within the peritoneal cavity, resulting in the downregulation of pro-inflammatory cytokines such as TNFα. In addition, in vivo DMOG treatment upregulates IL-10 expression, specifically in the peritoneal B-1 cell population. This study demonstrates cell type specific roles for hydroxylase inhibition in vivo and provides insight into the mechanism underlying the protection conveyed by DMOG in models of endotoxic shock

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Quasi-periodic acceleration of electrons by a plasmoid-driven shock in the solar atmosphere

Cosmic rays and solar energetic particles may be accelerated to relativistic energies by shock waves in astrophysical plasmas. On the Sun, shocks and particle acceleration are often associated with the eruption of magnetized plasmoids, called coronal mass ejections (CMEs). However, the physical relationship between CMEs and shock particle acceleration is not well understood. Here, we use extreme ultraviolet, radio and white-light imaging of a solar eruptive event on 22 September 2011 to show that a CME-induced shock (Alfvén Mach number 2:4+0:7 -0:8) was coincident with a coronal wave and an intense metric radio burst generated by intermittent acceleration of electrons to kinetic energies of 2{46 keV (0.1{0.4 c). Our observations show that plasmoid-driven quasi-perpendicular shocks are capable of producing quasi-periodic acceleration of electrons, an effect consistent with a turbulent or rippled plasma shock surface