7,077 research outputs found

    The role of hormones in sepsis: an integrated overview with a focus on mitochondrial and immune cell dysfunction

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    Sepsis is a dysregulated host response to infection that results in life-threatening organ dysfunction. Virtually every body system can be affected by this syndrome to greater or lesser extents. Gene transcription and downstream pathways are either up- or downregulated, albeit with considerable fluctuation over the course of the patient’s illness. This multi-system complexity contributes to a pathophysiology that remains to be fully elucidated. Consequentially, little progress has been made to date in developing new outcome-improving therapeutics. Endocrine alterations are well characterised in sepsis with variations in circulating blood levels and/or receptor resistance. However, little attention has been paid to an integrated view of how these hormonal changes impact upon the development of organ dysfunction and recovery. Here, we present a narrative review describing the impact of the altered endocrine system on mitochondrial dysfunction and immune suppression, two interlinked and key aspects of sepsis pathophysiology

    EquiFACS: the Equine Facial Action Coding System

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    Although previous studies of horses have investigated their facial expressions in specific contexts, e.g. pain, until now there has been no methodology available that documents all the possible facial movements of the horse and provides a way to record all potential facial configurations. This is essential for an objective description of horse facial expressions across a range of contexts that reflect different emotional states. Facial Action Coding Systems (FACS) provide a systematic methodology of identifying and coding facial expressions on the basis of underlying facial musculature and muscle movement. FACS are anatomically based and document all possible facial movements rather than a configuration of movements associated with a particular situation. Consequently, FACS can be applied as a tool for a wide range of research questions. We developed FACS for the domestic horse (Equus caballus) through anatomical investigation of the underlying musculature and subsequent analysis of naturally occurring behaviour captured on high quality video. Discrete facial movements were identified and described in terms of the underlying muscle contractions, in correspondence with previous FACS systems. The reliability of others to be able to learn this system (EquiFACS) and consistently code behavioural sequences was high—and this included people with no previous experience of horses. A wide range of facial movements were identified, including many that are also seen in primates and other domestic animals (dogs and cats). EquiFACS provides a method that can now be used to document the facial movements associated with different social contexts and thus to address questions relevant to understanding social cognition and comparative psychology, as well as informing current veterinary and animal welfare practices

    Chemical variation in a dominant tree species: population divergence, selection and genetic stability across environments

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    Understanding among and within population genetic variation of ecologically important plant traits provides insight into the potential evolutionary processes affecting those traits. The strength and consistency of selection driving variability in traits would be affected by plasticity in differences among genotypes across environments (G×E). We investigated population divergence, selection and environmental plasticity of foliar plant secondary metabolites (PSMs) in a dominant tree species, Eucalyptus globulus. Using two common garden trials we examined variation in PSMs at multiple genetic scales; among 12 populations covering the full geographic range of the species and among up to 60 families within populations. Significant genetic variation in the expression of many PSMs resides both among and within populations of E. globulus with moderate (e.g., sideroxylonal A h2op = 0.24) to high (e.g., macrocarpal G h2op = 0.48) narrow sense heritabilities and high coefficients of additive genetic variation estimated for some compounds. A comparison of Qst and Fst estimates suggest that variability in some of these traits may be due to selection. Importantly, there was no genetic by environment interaction in the expression of any of the quantitative chemical traits despite often significant site effects. These results provide evidence that natural selection has contributed to population divergence in PSMs in E. globulus, and identifies the formylated phloroglucinol compounds (particularly sideroxylonal) and a dominant oil, 1,8-cineole, as candidates for traits whose genetic architecture has been shaped by divergent selection. Additionally, as the genetic differences in these PSMs that influence community phenotypes is stable across environments, the role of plant genotype in structuring communities is strengthened and these genotypic differences may be relatively stable under global environmental changes

    Delivering the Future: Evaluation of a Multidisciplinary Clinical Leadership Programme in NHS Scotland.

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    The Delivering the Future (DtF) leadership programme was established in 2005 to strengthen senior clinical leadership capacity and capability across NHS Scotland. This paper reports on an evaluation of the programme to determine the extent to which the programme outcomes had been achieved. Sixty-seven (57%) programme participants responded to a questionnaire survey about their experience, and semi-structured interviews were conducted with participants (n=8) and senior leaders (n=7) at NHS Board level. The programme was highly regarded by participants and strategic level leads. The majority of DtF participants had been promoted or taken on expanded roles since completing the programme, taking on greater leadership responsibility. The programme was seen to be a significant influence on accelerating the progression of individuals to these roles, and in developing skills to perform at a senior leadership level. The significant investment in the programme was thought to be worthwhile in terms of wider benefits, albeit with a need to make better collective use of the alumni at a national level

    Vestibular Perception following Acute Unilateral Vestibular Lesions.

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    Little is known about the vestibulo-perceptual (VP) system, particularly after a unilateral vestibular lesion. We investigated vestibulo-ocular (VO) and VP function in 25 patients with vestibular neuritis (VN) acutely (2 days after onset) and after compensation (recovery phase, 10 weeks). Since the effect of VN on reflex and perceptual function may differ at threshold and supra-threshold acceleration levels, we used two stimulus intensities, acceleration steps of 0.5°/s(2) and velocity steps of 90°/s (acceleration 180°/s(2)). We hypothesised that the vestibular lesion or the compensatory processes could dissociate VO and VP function, particularly if the acute vertiginous sensation interferes with the perceptual tasks. Both in acute and recovery phases, VO and VP thresholds increased, particularly during ipsilesional rotations. In signal detection theory this indicates that signals from the healthy and affected side are still fused, but result in asymmetric thresholds due to a lesion-induced bias. The normal pattern whereby VP thresholds are higher than VO thresholds was preserved, indicating that any 'perceptual noise' added by the vertigo does not disrupt the cognitive decision-making processes inherent to the perceptual task. Overall, the parallel findings in VO and VP thresholds imply little or no additional cortical processing and suggest that vestibular thresholds essentially reflect the sensitivity of the fused peripheral receptors. In contrast, a significant VO-VP dissociation for supra-threshold stimuli was found. Acutely, time constants and duration of the VO and VP responses were reduced - asymmetrically for VO, as expected, but surprisingly symmetrical for perception. At recovery, VP responses normalised but VO responses remained shortened and asymmetric. Thus, unlike threshold data, supra-threshold responses show considerable VO-VP dissociation indicative of additional, higher-order processing of vestibular signals. We provide evidence of perceptual processes (ultimately cortical) participating in vestibular compensation, suppressing asymmetry acutely in unilateral vestibular lesions

    Transcriptional profiling of endobronchial ultrasound guided lymph node samples aids diagnosis of mediastinal lymphadenopathy

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    Background: Endobronchial ultrasound (EBUS) guided biopsy is the mainstay for investigation of mediastinal lymphadenopathy for laboratory diagnosis of malignancy, sarcoidosis or tuberculosis. However, improved methods for discriminating between tuberculosis and sarcoidosis and excluding malignancy are still needed. We sought to evaluate the role of genome-wide transcriptional profiling to aid diagnostic processes in this setting. Methods: Mediastinal lymph node samples from 88 individuals were obtained by EBUS guided aspiration for investigation of mediastinal lymphadenopathy and subjected to transcriptional profiling in addition to conventional laboratory assessments. Computational strategies were employed to evaluate the potential for using the transcriptome to distinguish between diagnostic categories. Results: Molecular signatures associated with granulomas or neoplastic and metastatic processes were clearly discernible in granulomatous and malignant lymph node samples respectively. Support vector machine (SVM) learning using differentially expressed genes showed excellent sensitivity and specificity profiles in receiver operating characteristic curve analysis with area under curve values >0.9 for discriminating between granulomatous and non-granulomatous disease, tuberculosis and sarcoidosis, and between cancer and reactive lymphadenopathy. A two-step decision tree using SVM to distinguish granulomatous and non-granulomatous disease, then between tuberculosis and sarcoidosis in granulomatous cases and between cancer and reactive lymphadenopathy in non-granulomatous cases achieved >90% specificity for each diagnosis and afforded greater sensitivity than existing tests to detect tuberculosis and cancer. In some diagnostically ambiguous cases computational classification predicted granulomatous disease or cancer before pathological abnormalities were evident. Conclusions: Machine learning analysis of transcriptional profiling in mediastinal lymphadenopathy may significantly improve the clinical utility of EBUS guided biopsies

    Optimizing Hybrid Spreading in Metapopulations.

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    Epidemic spreading phenomena are ubiquitous in nature and society. Examples include the spreading of diseases, information, and computer viruses. Epidemics can spread by local spreading, where infected nodes can only infect a limited set of direct target nodes and global spreading, where an infected node can infect every other node. In reality, many epidemics spread using a hybrid mixture of both types of spreading. In this study we develop a theoretical framework for studying hybrid epidemics, and examine the optimum balance between spreading mechanisms in terms of achieving the maximum outbreak size. We show the existence of critically hybrid epidemics where neither spreading mechanism alone can cause a noticeable spread but a combination of the two spreading mechanisms would produce an enormous outbreak. Our results provide new strategies for maximising beneficial epidemics and estimating the worst outcome of damaging hybrid epidemics
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