155 research outputs found

    Using InVivoStat to perform the statistical analysis of experiments

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    The need to improve reproducibility and reliability of animal experiments has led some journals to increase the stringency of the criteria that must be satisfied before manuscripts can be considered suitable for publication. In this article we give advice on experimental design, including minimum group sizes, calculating statistical power and avoiding pseudo-replication, which can improve reproducibility. We also give advice on normalisation, transformations, the gateway analysis of variance strategy and the use of p-values and confidence intervals. Applying all these statistical procedures correctly will strengthen the validity of the conclusions. We discuss how InVivoStat, a free-to-use statistical software package, which was designed for life scientists, especially animal researchers, can be used to help with these principles

    First report of generalized face processing difficulties in möbius sequence.

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    Reverse simulation models of facial expression recognition suggest that we recognize the emotions of others by running implicit motor programmes responsible for the production of that expression. Previous work has tested this theory by examining facial expression recognition in participants with Möbius sequence, a condition characterized by congenital bilateral facial paralysis. However, a mixed pattern of findings has emerged, and it has not yet been tested whether these individuals can imagine facial expressions, a process also hypothesized to be underpinned by proprioceptive feedback from the face. We investigated this issue by examining expression recognition and imagery in six participants with Möbius sequence, and also carried out tests assessing facial identity and object recognition, as well as basic visual processing. While five of the six participants presented with expression recognition impairments, only one was impaired at the imagery of facial expressions. Further, five participants presented with other difficulties in the recognition of facial identity or objects, or in lower-level visual processing. We discuss the implications of our findings for the reverse simulation model, and suggest that facial identity recognition impairments may be more severe in the condition than has previously been noted

    VLT/SINFONI time-resolved spectroscopy of the central, luminous, H-rich WN stars of R136

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    Using the Very Large Telescope's Spectrograph for INtegral Field Observation in the Near-Infrared (VLT/SINFONI), we have obtained repeated AO-assisted, NIR spectroscopy of the six central luminous, Wolf-Rayet (WR) stars in the core of the very young (~1 Myr), massive and dense cluster R136, in the Large Magellanic Cloud (LMC). We also de-archived available images that were obtained with the Hubble Space Telescope's Space Telescope Imaging Spectrograph (HST/STIS), and extracted high-quality, differential photometry of our target stars to check for any variability related to binary motion. Previous studies, relying on spatially unresolved, integrated, optical spectroscopy, had reported that one of these stars was likely to be a 4.377-day binary. Our study set out to identify the culprit and any other short-period system among our targets. However, none displays significant photometric variability, and only one star, BAT99-112 (R136c), located on the outer fringe of R136, displays a marginal variability in its radial velocities; we tentatively report an 8.2-day period. The binary status of BAT99-112 is supported by the fact that it is one of the brightest X-ray sources among all known WR stars in the LMC, consistent with it being a colliding-wind system. Follow-up observations have been proposed to confirm the orbital period of this potentially very massive system.Comment: 9 pages, 6 figures; accepted for publication in MNRA

    Estimating time-to-onset of adverse drug reactions from spontaneous reporting databases.

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    International audienceBACKGROUND: Analyzing time-to-onset of adverse drug reactions from treatment exposure contributes to meeting pharmacovigilance objectives, i.e. identification and prevention. Post-marketing data are available from reporting systems. Times-to-onset from such databases are right-truncated because some patients who were exposed to the drug and who will eventually develop the adverse drug reaction may do it after the time of analysis and thus are not included in the data. Acknowledgment of the developments adapted to right-truncated data is not widespread and these methods have never been used in pharmacovigilance. We assess the use of appropriate methods as well as the consequences of not taking right truncation into account (naĂŻve approach) on parametric maximum likelihood estimation of time-to-onset distribution. METHODS: Both approaches, naĂŻve or taking right truncation into account, were compared with a simulation study. We used twelve scenarios for the exponential distribution and twenty-four for the Weibull and log-logistic distributions. These scenarios are defined by a set of parameters: the parameters of the time-to-onset distribution, the probability of this distribution falling within an observable values interval and the sample size. An application to reported lymphoma after anti TNF-Âż treatment from the French pharmacovigilance is presented. RESULTS: The simulation study shows that the bias and the mean squared error might in some instances be unacceptably large when right truncation is not considered while the truncation-based estimator shows always better and often satisfactory performances and the gap may be large. For the real dataset, the estimated expected time-to-onset leads to a minimum difference of 58 weeks between both approaches, which is not negligible. This difference is obtained for the Weibull model, under which the estimated probability of this distribution falling within an observable values interval is not far from 1. CONCLUSIONS: It is necessary to take right truncation into account for estimating time-to-onset of adverse drug reactions from spontaneous reporting databases

    Developing and implementing an integrated delirium prevention system of care:a theory driven, participatory research study

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    Background: Delirium is a common complication for older people in hospital. Evidence suggests that delirium incidence in hospital may be reduced by about a third through a multi-component intervention targeted at known modifiable risk factors. We describe the research design and conceptual framework underpinning it that informed the development of a novel delirium prevention system of care for acute hospital wards. Particular focus of the study was on developing an implementation process aimed at embedding practice change within routine care delivery. Methods: We adopted a participatory action research approach involving staff, volunteers, and patient and carer representatives in three northern NHS Trusts in England. We employed Normalization Process Theory to explore knowledge and ward practices on delirium and delirium prevention. We established a Development Team in each Trust comprising senior and frontline staff from selected wards, and others with a potential role or interest in delirium prevention. Data collection included facilitated workshops, relevant documents/records, qualitative one-to-one interviews and focus groups with multiple stakeholders and observation of ward practices. We used grounded theory strategies in analysing and synthesising data. Results: Awareness of delirium was variable among staff with no attention on delirium prevention at any level; delirium prevention was typically neither understood nor perceived as meaningful. The busy, chaotic and challenging ward life rhythm focused primarily on diagnostics, clinical observations and treatment. Ward practices pertinent to delirium prevention were undertaken inconsistently. Staff welcomed the possibility of volunteers being engaged in delirium prevention work, but existing systems for volunteer support were viewed as a barrier. Our evolving conception of an integrated model of delirium prevention presented major implementation challenges flowing from minimal understanding of delirium prevention and securing engagement of volunteers alongside practice change. The resulting Prevention of Delirium (POD) Programme combines a multi-component delirium prevention and implementation process, incorporating systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Conclusions: Although our substantive interest was in delirium prevention, the conceptual and methodological strategies pursued have implications for implementing and sustaining practice and service improvements more broadly

    Modeling the factors that influence exposure to SARS-CoV-2 on a subway train carriage

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    We propose the Transmission of Virus in Carriages (TVC) model, a computational model which simulates the potential exposure to SARS-CoV-2 for passengers traveling in a subway rail system train. This model considers exposure through three different routes: fomites via contact with contaminated surfaces; close-range exposure, which accounts for aerosol and droplet transmission within 2 m of the infectious source; and airborne exposure via small aerosols which does not rely on being within 2 m distance from the infectious source. Simulations are based on typical subway parameters and the aim of the study is to consider the relative effect of environmental and behavioral factors including prevalence of the virus in the population, number of people traveling, ventilation rate, and mask wearing as well as the effect of model assumptions such as emission rates. Results simulate generally low exposures in most of the scenarios considered, especially under low virus prevalence. Social distancing through reduced loading and high mask-wearing adherence is predicted to have a noticeable effect on reducing exposure through all routes. The highest predicted doses happen through close-range exposure, while the fomite route cannot be neglected; exposure through both routes relies on infrequent events involving relatively few individuals. Simulated exposure through the airborne route is more homogeneous across passengers, but is generally lower due to the typically short duration of the trips, mask wearing, and the high ventilation rate within the carriage. The infection risk resulting from exposure is challenging to estimate as it will be influenced by factors such as virus variant and vaccination rates

    The stellar and sub-stellar IMF of simple and composite populations

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    The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

    Manipulation of an Innate Escape Response in Drosophila: Photoexcitation of acj6 Neurons Induces the Escape Response

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    Background: The genetic analysis of behavior in Drosophila melanogaster has linked genes controlling neuronal connectivity and physiology to specific neuronal circuits underlying a variety of innate behaviors. We investigated the circuitry underlying the adult startle response, using photoexcitation of neurons that produce the abnormal chemosensory jump 6 (acj6) transcription factor. This transcription factor has previously been shown to play a role in neuronal pathfinding and neurotransmitter modality, but the role of acj6 neurons in the adult startle response was largely unknown. Principal Findings: We show that the activity of these neurons is necessary for a wild-type startle response and that excitation is sufficient to generate a synthetic escape response. Further, we show that this synthetic response is still sensitive to the dose of acj6 suggesting that that acj6 mutation alters neuronal activity as well as connectivity and neurotransmitter production. Results/Significance: These results extend the understanding of the role of acj6 and of the adult startle response in general. They also demonstrate the usefulness of activity-dependent characterization of neuronal circuits underlying innat

    'Dressed in a Little Brief Authority': Authority Before, During, and After Shakespeare's Plays

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    This essay discusses the concept of authority from Shakespeare’s time to our own, considers examples of Shakespeare’s own explorations of authority, and provides a concise history of the ways in which Shakespeare has been constructed as cultural authority in different historical periods. It summarises the essays contained in the book, and argues that the book illuminates not only how Shakespeare became the archetypal figure of English cultural authority, but, perhaps more interestingly, why
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