76 research outputs found

    Molecular Embedding via a Second Order Dissimilarity Parameterized Approach

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    The influence of contextual factors on healthcare quality improvement initiatives:a realist review

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    Background Recognising the influence of context and the context-sensitive nature of quality improvement (QI) interventions is crucial to implementing effective improvements and successfully replicating them in new settings, yet context is still poorly understood. To address this challenge, it is necessary to capture generalisable knowledge, first to understand which aspects of context are most important to QI and why, and secondly, to explore how these factors can be managed to support healthcare improvement, in terms of implementing successful improvement initiatives, achieving sustainability and scaling interventions. The research question was how and why does context influence quality improvement initiatives in healthcare? Methods A realist review explored the contextual conditions that influence healthcare improvement. Realist methodology integrates theoretical understanding and stakeholder input with empirical research findings. The review aimed to identify and understand the role of context during the improvement cycle, i.e. planning, implementation, sustainability and transferability; and distil new knowledge to inform the design and development of context-sensitive QI initiatives. We developed a preliminary theory of the influence of context to arrive at a conceptual and theoretical framework. Results Thirty-five studies were included in the review, demonstrating the interaction of key contextual factors across healthcare system levels during the improvement cycle. An evidence-based explanatory theoretical model is proposed to illustrate the interaction between contextual factors, system levels (macro, meso, micro) and the stages of the improvement journey. Findings indicate that the consideration of these contextual factors would enhance the design and delivery of improvement initiatives, across a range of improvement settings. Conclusions This is the first realist review of context in QI and contributes to a deeper understanding of how context influences quality improvement initiatives. The distillation of key contextual factors offers the potential to inform the design and development of context-sensitive interventions to enhance improvement initiatives and address the challenge of spread and sustainability. Future research should explore the application of our conceptual model to enhance improvement-planning processes

    New leaders in Early Years: making a difference for children in England

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    This paper examines the extent by which the four domains of the sustainable early childhood leadership model were evident in the experiences of New Leaders in Early Years (NLEY) participants. This original piece of research explores the impact of pedagogical leadership and focuses on participants recruited to a national pilot to make a difference for children in areas of social disadvantage in England. The significance of this paper is timely given the continued focus on leadership, evidenced in the ‘Early Years Workforce Strategy’ (2017). This paper contributes a conceptual framework for early childhood leadership as a methodological tool to make sense of the data. The findings suggest that NLEY did have an impact on the settings and the families they were working with and that the conceptual framework for early childhood leadership was an effective tool for making sense of their journey from novice to leader

    Functional Characterization of the Dendritically Localized mRNA Neuronatin in Hippocampal Neurons

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    Local translation of dendritic mRNAs plays an important role in neuronal development and synaptic plasticity. Although several hundred putative dendritic transcripts have been identified in the hippocampus, relatively few have been verified by in situ hybridization and thus remain uncharacterized. One such transcript encodes the protein neuronatin. Neuronatin has been shown to regulate calcium levels in non-neuronal cells such as pancreatic or embryonic stem cells, but its function in mature neurons remains unclear. Here we report that neuronatin is translated in hippocampal dendrites in response to blockade of action potentials and NMDA-receptor dependent synaptic transmission by TTX and APV. Our study also reveals that neuronatin can adjust dendritic calcium levels by regulating intracellular calcium storage. We propose that neuronatin may impact synaptic plasticity by modulating dendritic calcium levels during homeostatic plasticity, thereby potentially regulating neuronal excitability, receptor trafficking, and calcium dependent signaling

    Transcriptome Analysis of Synaptoneurosomes Identifies Neuroplasticity Genes Overexpressed in Incipient Alzheimer's Disease

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    In Alzheimer's disease (AD), early deficits in learning and memory are a consequence of synaptic modification induced by toxic beta-amyloid oligomers (oAβ). To identify immediate molecular targets downstream of oAβ binding, we prepared synaptoneurosomes from prefrontal cortex of control and incipient AD (IAD) patients, and isolated mRNAs for comparison of gene expression. This novel approach concentrates synaptic mRNA, thereby increasing the ratio of synaptic to somal mRNA and allowing discrimination of expression changes in synaptically localized genes. In IAD patients, global measures of cognition declined with increasing levels of dimeric Aβ (dAβ). These patients also showed increased expression of neuroplasticity related genes, many encoding 3′UTR consensus sequences that regulate translation in the synapse. An increase in mRNA encoding the GluR2 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) was paralleled by elevated expression of the corresponding protein in IAD. These results imply a functional impact on synaptic transmission as GluR2, if inserted, maintains the receptors in a low conductance state. Some overexpressed genes may induce early deficits in cognition and others compensatory mechanisms, providing targets for intervention to moderate the response to dAβ

    Introduction to the special issue on the statistical mechanics of climate

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    We introduce the special issue on the Statistical Mechanics of Climate by presenting an informal discussion of some theoretical aspects of climate dynamics that make it a topic of great interest for mathematicians and theoretical physicists. In particular, we briefly discuss its nonequilibrium and multiscale properties, the relationship between natural climate variability and climate change, the different regimes of climate response to perturbations, and critical transitions
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