4,387 research outputs found

    A model and architecture for situation determination

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    Automatically determining the situation of an ad-hoc group of people and devices within a smart environment is a significant challenge in pervasive computing systems. Current approaches often rely on an environment expert to correlate the situations that occur with the available sensor data, while other machine learning based approaches require long training periods before the system can be used. Furthermore, situations are commonly recognised at a low-level of granularity, which limits the scope of situation-aware applications. This paper presents a novel approach to situation determination that attempts to overcome these issues by providing a reusable library of general situation specifications that can be easily extended to create new specific situations, and immediately deployed without the need of an environment expert. A proposed architecture of an accompanying situation determination middleware is provided, as well as an analysis of a prototype implementation

    Guiding adults impartially : a Scottish study

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    In Scotland, the development of guidance for adults has been significant in the last few years. A 1992 Inspectorate report concluded that: 'Considerable progress has been made in developing effective arrangements for student guidance' (SOED, 1992: 36). However, the same document also called for improved pre-entry guidance and better course induction, the development of policy statements on guidance, and the commitment of resources to improving facilities, staff training and advocating. Since 1993, the Scottish Office-backed Adult Guidance Initiative-Scotland (AEGIS) has been responsible for raising awareness about good practice in guidance, and has produced policy documents and staff development materials on quality assurance and networking and held a number of national conferences. Researchers at the Scottish Council for Research in Education published four major studies in 1993-4, describing the experiences of adult returners, patterns of progression in post-school education and adult guidance practice. In 1996, the Scottish Office published strategy proposals for adult guidance, to include a telephone helpline (SOEID, 1996). TI1is was followed by an action plan on lifelong learning and guidance, including support for local guidance networks and increased marketing of learning opportunities (SOEID, 1997a and 1997b). Further research reports on the provision of guidance as part of access to higher education in Scotland were also published in 1996 (Blencowe et al, 1996; Blair and Tett, 1996). This article is based on research carried out to investigate the extent to which the principle of impartiality is perceived to be relevant and applicable by guidance practitioners in their work with adults. Guidance professionals have drawn attention to the importance of impartiality as a basic principle governing their practice. Also, the imperative of giving adults information and advice which is impartial and not influenced, for example, by recruitment targets for courses, is stressed in statements of good practice and practitioners' charters. The person-centred counselling approach underpinning these statements and charters tends to be strongly 'non-directive'. Guidance services have developed considerably in the last few years, but there is increasing competition between course providers and this has raised concerns about jeopardising impartiality

    Peripheral inflammation is associated with remote global gene expression changes in the brain

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    Background: Although the central nervous system (CNS) was once considered an immunologically privileged site, in recent years it has become increasingly evident that cross talk between the immune system and the CNS does occur. As a result, patients with chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease or psoriasis, are often further burdened with neuropsychiatric symptoms, such as depression, anxiety and fatigue. Despite the recent advances in our understanding of neuroimmune communication pathways, the precise effect of peripheral immune activation on neural circuitry remains unclear. Utilizing transcriptomics in a well-characterized murine model of systemic inflammation, we have started to investigate the molecular mechanisms by which inflammation originating in the periphery can induce transcriptional modulation in the brain.<p></p> Methods: Several different systemic and tissue-specific models of peripheral toll-like-receptor-(TLR)-driven (lipopolysaccharide (LPS), lipoteichoic acid and Imiquimod) and sterile (tumour necrosis factor (TNF) and 12-O-tetradecanoylphorbol-13-acetate (TPA)) inflammation were induced in C57BL/6 mice. Whole brain transcriptional profiles were assessed and compared 48 hours after intraperitoneal injection of lipopolysaccharide or vehicle, using Affymetrix GeneChip microarrays. Target gene induction, identified by microarray analysis, was validated independently using qPCR. Expression of the same panel of target genes was then investigated in a number of sterile and other TLR-dependent models of peripheral inflammation.<p></p> Results: Microarray analysis of whole brains collected 48 hr after LPS challenge revealed increased transcription of a range of interferon-stimulated genes (ISGs) in the brain. In addition to acute LPS challenge, ISGs were induced in the brain following both chronic LPS-induced systemic inflammation and Imiquimod-induced skin inflammation. Unique to the brain, this transcriptional response is indicative of peripherally triggered, interferon-mediated CNS inflammation. Similar models of sterile inflammation and lipoteichoic-acid-induced systemic inflammation did not share the capacity to trigger ISG induction in the brain.<p></p> Conclusions: These data highlight ISG induction in the brain as being a consequence of a TLR-induced type I interferon response. As considerable evidence links type I interferons to psychiatric disorders, we hypothesize that interferon production in the brain could represent an important mechanism, linking peripheral TLR-induced inflammation with behavioural changes.<p></p&gt

    Ready for a paradigm shift? Part 2: Introducing qualitative research methodologies and methods

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    This paper explores a number of commonly used methodologies and methods in qualitative research, namely grounded theory, case study, phenomenology, ethnography and narrative research. For each methodology a brief history of its development and variants is given, followed by typical methods of data collection and analysis. Examples of manual therapy qualitative research studies are highlighted for each methodology. Data collection methods are then discussed and include individual interviews, focus groups, observation and documentary analysis. A frequently used method of data analysis, thematic analysis, is briefly explained. Finally, the strategies to enhance the quality of qualitative research is explored and compared to those of quantitative research. © 2012 Elsevier Ltd

    Sustained exposure to systemic endotoxin triggers chemokine induction in the brain followed by a rapid influx of leukocytes

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    Background: Recent years have seen an explosion of research pertaining to biological psychiatry, yet despite subsequent advances in our understanding of neuroimmune communication pathways, how the brain senses and responds to peripheral inflammation remains poorly understood. A better understanding of these pathways may be important for generating novel therapeutics to treat many patients with chronic inflammatory diseases who also suffer from neuropsychiatric comorbidities. Here we have systematically assessed the leukocyte infiltrate to the brain following systemic endotoxin exposure to better understand this novel route of neuroimmune communication. Methods: Mice were injected intraperitoneally with LPS daily for 2, 5 or 7 consecutive days. We systematically interrogated the subsequent induction of chemokine transcription in the brain using TaqMan low-density arrays. A combination of flow cytometry and immunohistochemistry was then used to characterise the accompanying leukocyte infiltrate Result: Repeated LPS challenges resulted in prolonged activation of brain-resident microglia, coupled with an increased local transcription of numerous chemokines. After 2 days of administering LPS, there was a marked increase in the expression of the neutrophil chemoattractants CXCL1 and CXCL2; the monocyte chemoattractants CCL2, CCL5, CCL7 and CCL8; and the lymphocyte chemoattractants CXCL9, CXCL10 and CXCL16. In a number of cases, this response was sustained for several days. Chemokine induction was associated with a transient recruitment of neutrophils and monocytes to the brain, coupled with a sustained accumulation of macrophages, CD8+ T cells, NK cells and NKT cells. Strikingly, neutrophils, monocytes and T cells appeared to extravasate from the vasculature and/or CSF to infiltrate the brain parenchyma. Conclusions: Prolonged exposure to a peripheral inflammatory stimulus triggers the recruitment of myeloid cells and lymphocytes to the brain. By altering the inflammatory or metabolic milieu of the brain, this novel method of immune-to-brain communication may have profound implications for patients with chronic inflammatory diseases, potentially leading to neuropsychiatric comorbidities

    Low Dimensionality in Gene Expression Data Enables the Accurate Extraction of Transcriptional Programs from Shallow Sequencing

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    A tradeoff between precision and throughput constrains all biological measurements, including sequencing-based technologies. Here, we develop a mathematical framework that defines this tradeoff between mRNA-sequencing depth and error in the extraction of biological information. We find that transcriptional programs can be reproducibly identified at 1% of conventional read depths. We demonstrate that this resilience to noise of “shallow” sequencing derives from a natural property, low dimensionality, which is a fundamental feature of gene expression data. Accordingly, our conclusions hold for ∌350 single-cell and bulk gene expression datasets across yeast, mouse, and human. In total, our approach provides quantitative guidelines for the choice of sequencing depth necessary to achieve a desired level of analytical resolution. We codify these guidelines in an open-source read depth calculator. This work demonstrates that the structure inherent in biological networks can be productively exploited to increase measurement throughput, an idea that is now common in many branches of science, such as image processing

    Optogenetic investigation of cortical network dynamics in epilepsy

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    Ph. D. ThesisUnderstanding the cortical network properties which determine the susceptibility of cortex to the onset of seizures remains a major goal of epilepsy research. The determinants of seizure risk in cortical networks are dynamic, showing dependency on intrinsic cortical activity and environmental influences. The failure to identify reliable electrographic indicators of imminent seizure onset suggests that the contributory factors may not be electrographically obvious. A strong candidate for such a property is the activity dependent disinhibition of the excitatory network which results from increases in intracellular chloride concentration. Chloride loading has been shown previously to occur during periods of intense neuronal activity, resulting from concomitant excitatory and inhibitory synaptic transmission. To explore how network dynamics evolve from a stable healthy state to one permissive for the onset and propagation of seizures, I used an optogenetic approach to selectively interrogate dynamic changes to excitatory transmission between the principal cells of the cortical circuit following an acute ictogenic challenge, both in vitro and in vivo. Using ultra-low frequency optogenetic stimulation genetically targeted to the pyramidal cells of neocortex, I demonstrate that epileptiform activity, which develops spontaneously following an acute chemoconvulsant challenge, can both be reduced and monitored, using an active probing strategy. Delivering continuous and focal optogenetic stimulations to superficial neocortex and regions of the hippocampal formation evokes glutamatergic responses in the LFP which can be used to assay dendritic excitability in the network. At ultralow frequencies, between 0.1-0.033 Hz, optogenetic stimulation markedly reduced the rate of evolution of epileptiform activity, when delivered to neocortex or hippocampal structures, in acutely prepared adult mouse brain slices bathed in 0Mg2+ perfusate. The response evoked by these test pulses undergoes an all-or-nothing transformation observable in the LFP which reliably telegraphed the onset of ictal activity in two models of epilepsy. Using electrophysiological tools and 2-photon calcium imaging of individual dendrites, I demonstrate that this phenomenon likely reflects a reduction in the threshold for dendritic spikes. Using an anatomically realistic computational model pyramidal cell I show that this effect is reproduced by modest positive shifts in the GABAergic reversal potential in distal pyramidal cell dendrites. Finally, I report preliminary data demonstrating a potential mechanism for the diurnal modulation of seizure risk. Diurnal periodicity in seizure susceptibility have been observed longitudinal recordings from both patients and chronically epileptic experimental animals. Using the optical chloride sensor ClopHensor I examine steady-state pyramidal cell chloride concentration over the diurnal period and show that periodicity in chloride homeostasis is consistent with the phase of diurnally modulated seizure risk. In this thesis I use a range of optical and electrophysiological tools to explore the contribution of dynamic chloride concentration in pyramidal cells in determining cortical susceptibility to seizures onset. Using two acute epilepsy models I demonstrate that an assayable increase in dendritic excitability precedes ictogenesis, and demonstrate a potential mechanism by which variation in [Cl-]i can give rise to this effect. I go on to show diurnal variation in [Cl-]i in cortical pyramidal cells, and link this to circadian modulation of susceptibility to chemoconvulsants, suggesting a functional mechanism for the dynamic seizure risk observed in epileptic patients

    Secondary head teachers as leaders for learning: perceptions and practices of leadership focused on learning and teaching

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    The key rationale behind this primarily instrumental case study (in three Scottish secondary schools) was the need to comprehend more clearly the scope, nature and influence of secondary Head Teachers’ leadership for learning. This is generally understood as leadership that is directed at the learning of pupils and the teaching of teachers. Crucially, it is also concerned with influencing the conditions that nurture and support these. Leadership for learning underpins the Scottish Standard for Headship (General Teaching Council Scotland, 2012), designed to support the learning and self-evaluation of Head Teachers. Within existing literature there is a need for more information on the practice of leadership for learning, particularly around what it is that Head Teachers actually do in practice that is focused on improving learning and teaching (Kalman and Arslan, 2016; Hitt and Player, 2018; Nuemerski, 2013). This study provides a more detailed understanding of the how of leadership focused on learning and teaching. This study explored how three Scottish secondary Head Teachers conceptualised their role as leaders for learning in their schools, their perceptions around the operationalisation of this role and the scope and nature of this leadership according to teachers. Using a qualitative interpretivist approach, semi-structured interviews were conducted with Head Teachers and teachers from three very different state schools. Each Head Teacher was selected on the basis of evidence which indicated that they were both very knowledgeable about leadership for learning and also that it was a key focus of their practice. Head Teacher perceptions were sought through two interviews each, one at the start of the research process in each school and a final one, conducted on completion of all the teacher interviews. A total of 19 teachers were interviewed and data from these interviews, and the Head Teacher interviews, were analysed thematically. Teacher respondents were representative of roles across the school: unpromoted teachers, middle leaders and Depute Head Teachers. In addition, emails from several interviewees following the interview process were added to the data base. Documentation was also gathered in the interest of providing context to help make sense of some of the data A number of key and overlapping themes were identified from the interviews. An emerging theme from all participants’ testimonies was the identification of each Head Teacher as a leader with improving learning and teaching as their key priority, particularly through an inclusive focus on meeting the needs of each and every pupil. The development of a shared whole school vision about what effective learning and teaching meant in practice was prioritised in all three schools, with particular examples of each Head Teacher’s actions in this area. This was supported by a Head Teacher focus on growing capacity and capability across the schools through a variety of mechanisms including: supporting teacher learning, collaboration and engagement; engaging the middle leader structure; and endeavouring to ensure coherence across concurrent developments. A marked feature of each Head Teacher’s work was ensuring that all of these were focused in the service of improving learning and teaching. Four themes arose from the interviews which appear particularly significant to the way each Head Teacher led developments in learning and teaching, themes that are either under-theorised in the educational leadership literature or are areas of contention. These were: i) Head Teachers’ frequent engagement in reciprocal dialogues with teachers around learning and teaching matters; ii) each Head Teacher staying in close proximity to the practice of learning and teaching in a number of significant ways; iii) the important role of each Head Teacher’s knowledge and understanding about learning and teaching; and related to this, iv) the Head Teacher’s role as lead learner in the school. This study found that all four underpinned each Head Teacher’s leadership for learning, thinking and practice. In the present Scottish policy climate, where Head Teachers are expected to be leaders for learning, this study provides timely empirical evidence of how some Head Teachers are putting this into operation with, and through, the colleagues for whom they have leadership responsibility. Using the perceptions of both teachers and Head Teachers, this study adds to knowledge by providing deeper understanding of Head Teacher leadership for learning practice in the Scottish secondary context. It provides detailed analysis of particular key practices, highlighting the importance and enactment of some key reciprocal relationships focused on learning and teaching that each Head Teacher had with teachers

    A SQUAMOSA MADS-box gene involved in the regulation of anthocyanin accumulation in bilberry fruits

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    Anthocyanins are important health promoting phytochemicals that are abundant in many fleshy fruits. Bilberry (Vaccinium myrtillus L.) is one of the best sources of these compounds. Here we report on the expression pattern and functional analysis of a SQUAMOSA (SQUA) class MADS-box transcription factor, VmTDR4, associated with anthocyanin biosynthesis in bilberry. Levels of VmTDR4 expression were spatially and temporally linked with colour development and anthocyanin-related gene expression. Virus induced gene silencing (VIGS) was used to suppress VmTDR4 expression in bilberry resulting in substantial reduction in anthocyanin levels in fully ripe fruits. Chalcone synthase was used a positive control in the VIGS experiments. Additionally, in sectors of fruit tissue in which the expression of the VmTDR4 gene was silenced, the expression of R2R3 MYB family transcription factors related to the biosynthesis of flavonoids were also altered. We conclude that VmTDR4 plays an important role in the accumulation of anthocyanins during normal ripening in bilberry; probably through direct or indirect control of transcription factors belonging to the R2R3 MYB family

    Introduction of a modified obstetric early warning system ­(­MOEWS­)­ at an Ethiopian referral hospital : a feasibility assessment

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    Acknowledgments The authors wish to acknowledge Johnson & Johnson and THET for funding this project and the staff and management of Felege Hiwot Referral Hospital for their support throughout the project. Funding: This project was supported by THET Strengthening Surgical Capacity grant SSC 4.1 funded by Johnson & Johnson.Peer reviewedPublisher PD
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