High-precision polarimetry of nearby stars (d < 50 pc): Mapping the interstellar dust and magnetic field inside the Local Bubble

Context:We investigate the linear polarization produced by interstellar dust aligned by the magnetic field in the solar neighborhood (d Aims: We aim to detect and map dust clouds which give rise to statistically significant amounts of polarization of the starlight passing through the cloud, and to determine the interstellar magnetic field direction from the position angle of the observed polarization.Methods: High-precision broad-band (BV R) polarization observations are made of 361 stars in spectral classes F to G, with detection sensitivity at the level of or better than 10−5 (0.001%). The sample consists of 125 stars in the magnitude range 6–9 observed at the 2.2 m UH88 telescope on Mauna Kea, 205 stars in the magnitude range 3–6 observed at the Japanese (Tohoku) T60 telescope on Haleakala, and 31 stars in the magnitude range 4–7 observed at the 1.27 m H127 telescope of the Greenhill Observatory, Tasmania. Identical copies of the Dipol-2 polarimeter are used on these three sites.Results: Statistically significant (>3σ) polarization is found in 115 stars, and >2σ detection in 178 stars, out of the total sample of 361 stars. Polarization maps based on these data show filament-like patterns of polarization position angles, which are related to both the heliosphere geometry, the kinematics of nearby clouds, and the Interstellar Boundary EXplorer ribbon magnetic field. From long-term multiple observations, a number (~20) of stars show evidence of intrinsic variability at the 10−5 level. This can be attributed to circumstellar effects (e.g., debris disks and chromospheric activity). The star HD 101805 shows a peculiar wavelength dependence, indicating size distribution of scattering particles different from that of a typical interstellar medium. Our high signal-to-noise measurements of nearby stars with very low polarization also provide a useful dataset for calibration purposes

An Action-Based Approach to Presence: Foundations and Methods

This chapter presents an action-based approach to presence. It starts by briefly describing the theoretical and empirical foundations of this approach, formalized into three key notions of place/space, action and mediation. In the light of these notions, some common assumptions about presence are then questioned: assuming a neat distinction between virtual and real environments, taking for granted the contours of the mediated environment and considering presence as a purely personal state. Some possible research topics opened up by adopting action as a unit of analysis are illustrated. Finally, a case study on driving as a form of mediated presence is discussed, to provocatively illustrate the flexibility of this approach as a unified framework for presence in digital and physical environment

Pharmacokinetics and metabolism of 13-cis-retinoic acid (isotretinoin) in children with high-risk neuroblastoma – a study of the United Kingdom Children's Cancer Study Group

The administration of 13-cis-retinoic acid (13-cisRA), following myeloablative therapy improves 3-year event-free survival rates in children with high-risk neuroblastoma. This study aimed to determine the degree of inter-patient pharmacokinetic variation and extent of metabolism in children treated with 13-cisRA. 13-cis-retinoic acid (80 mg m−2 b.d.) was administered orally and plasma concentrations of parent drug and metabolites determined on days 1 and 14 of courses 2, 4 and 6 of treatment. Twenty-eight children were studied. The pharmacokinetics of 13-cisRA were best described by a modified one-compartment, zero-order absorption model combined with lag time. Mean population pharmacokinetic parameters included an apparent clearance of 15.9 l h−1, apparent volume of distribution of 85 l and absorption lag time of 40 min with a large inter-individual variability associated with all parameters (coefficients of variation greater than 50%). Day 1 peak 13-cisRA levels and exposure (AUC) were correlated with method of administration (P<0.02), with 2.44- and 1.95-fold higher parameter values respectively, when 13-cisRA capsules were swallowed as opposed to being opened and the contents mixed with food before administration. Extensive accumulation of 4-oxo-13-cisRA occurred during each course of treatment with plasma concentrations (mean±s.d. 4.67±3.17 μM) higher than those of 13-cisRA (2.83±1.44 μM) in 16 out of 23 patients on day 14 of course 2. Extensive metabolism to 4-oxo-13-cisRA may influence pharmacological activity of 13-cisRA

A New Model of Delirium Care in the Acute Geriatric Setting: Geriatric Monitoring Unit

<p>Abstract</p> <p>Background</p> <p>Delirium is a common and serious condition, which affects many of our older hospitalised patients. It is an indicator of severe underlying illness and requires early diagnosis and prompt treatment, associated with poor survival, functional outcomes with increased risk of institutionalisation following the delirium episode in the acute care setting. We describe a new model of delirium care in the acute care setting, titled Geriatric Monitoring Unit (GMU) where the important concepts of delirium prevention and management are integrated. We hypothesize that patients with delirium admitted to the GMU would have better clinical outcomes with less need for physical and psychotropic restraints compared to usual care.</p> <p>Methods/Design</p> <p>GMU models after the Delirium Room with adoption of core interventions from Hospital Elder Life Program and use of evening bright light therapy to consolidate circadian rhythm and improve sleep in the elderly patients. The novelty of this approach lies in the amalgamation of these interventions in a multi-faceted approach in acute delirium management. GMU development thus consists of key considerations for room design and resource planning, program specific interventions and daily core interventions. Assessments undertaken include baseline demographics, comorbidity scoring, duration and severity of delirium, cognitive, functional measures at baseline, 6 months and 12 months later. Additionally we also analysed the pre and post-GMU implementation knowledge and attitude on delirium care among staff members in the geriatric wards (nurses, doctors) and undertook satisfaction surveys for caregivers of patients treated in GMU.</p> <p>Discussion</p> <p>This study protocol describes the conceptualization and implementation of a specialized unit for delirium management. We hypothesize that such a model of care will not only result in better clinical outcomes for the elderly patient with delirium compared to usual geriatric care, but also improved staff knowledge and satisfaction. The model may then be transposed across various locations and disciplines in the acute hospital where delirious patients could be sited.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN52323811">ISRCTN52323811</a></p

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Application of site and haplotype-frequency based approaches for detecting selection signatures in cattle

<p>Abstract</p> <p>Background</p> <p>'Selection signatures' delimit regions of the genome that are, or have been, functionally important and have therefore been under either natural or artificial selection. In this study, two different and complementary methods--integrated Haplotype Homozygosity Score (|iHS|) and population differentiation index (F_ST)--were applied to identify traces of decades of intensive artificial selection for traits of economic importance in modern cattle.</p> <p>Results</p> <p>We scanned the genome of a diverse set of dairy and beef breeds from Germany, Canada and Australia genotyped with a 50 K SNP panel. Across breeds, a total of 109 extreme |iHS| values exceeded the empirical threshold level of 5% with 19, 27, 9, 10 and 17 outliers in Holstein, Brown Swiss, Australian Angus, Hereford and Simmental, respectively. Annotating the regions harboring clustered |iHS| signals revealed a panel of interesting candidate genes like SPATA17, MGAT1, PGRMC2 and ACTC1, COL23A1, MATN2, respectively, in the context of reproduction and muscle formation. In a further step, a new Bayesian F_ST-based approach was applied with a set of geographically separated populations including Holstein, Brown Swiss, Simmental, North American Angus and Piedmontese for detecting differentiated loci. In total, 127 regions exceeding the 2.5 per cent threshold of the empirical posterior distribution were identified as extremely differentiated. In a substantial number (56 out of 127 cases) the extreme F_STvalues were found to be positioned in poor gene content regions which deviated significantly (p < 0.05) from the expectation assuming a random distribution. However, significant F_STvalues were found in regions of some relevant genes such as SMCP and FGF1.</p> <p>Conclusions</p> <p>Overall, 236 regions putatively subject to recent positive selection in the cattle genome were detected. Both |iHS| and F_STsuggested selection in the vicinity of the Sialic acid binding Ig-like lectin 5 gene on BTA18. This region was recently reported to be a major QTL with strong effects on productive life and fertility traits in Holstein cattle. We conclude that high-resolution genome scans of selection signatures can be used to identify genomic regions contributing to within- and inter-breed phenotypic variation.</p

Isoniazid preventive treatment among child contacts of adults with smear-positive tuberculosis in The Gambia.

Setting: Greater Banjul area of The Gambia. Objectives: To evaluate uptake, adherence and completion of treatment among tuberculosis (TB) exposed children in The Gambia when isoniazid preventive treatment (IPT) is delivered at home Design: Child (age <5 years) contacts of adults with smear-positive TB were prospectively enrolled. Following symptom screening, tuberculin skin testing and clinical evaluation where indicated, those without disease were placed on daily isoniazid, provided monthly at home. Adherence was assessed by pill counts and IsoScreen™ urine test. Results: Of 404 contacts aged <5 years, 368 (91.1%) were offered IPT. Of the 328 (89.4%) for whom consent was received and who commenced IPT, 18 (5.5%) dropped out and 310 (94.5%) remained on IPT to the end of the 6-month regimen. Altogether, 255/328 children (77.7%, 95%CI 73.2-82.2) completed all 6 months, with good adherence. The IsoScreen test was positive in 85.3% (435/510) of all tests among those defined as having good adherence by pill count and in 16% (8/50) of those defined as having poor adherence (P < 0.001). A cascade of care analysis showed an overall completion rate with good adherence of 61% for all child contacts. Conclusion: Home-delivered IPT among child contacts of adults with smear-positive TB in The Gambia achieved verifiable high uptake and adherence rates. System rather than patient factors are likely to determine the success of IPT at national level

Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments

The Number and Transmission of [PSI+] Prion Seeds (Propagons) in the Yeast Saccharomyces cerevisiae

Yeast (Saccharomyces cerevisiae) prions are efficiently propagated and the on-going generation and transmission of prion seeds (propagons) to daughter cells during cell division ensures a high degree of mitotic stability. The reversible inhibition of the molecular chaperone Hsp104p by guanidine hydrochloride (GdnHCl) results in cell division-dependent elimination of yeast prions due to a block in propagon generation and the subsequent dilution out of propagons by cell division.Analysing the kinetics of the GdnHCl-induced elimination of the yeast [PSI+] prion has allowed us to develop novel statistical models that aid our understanding of prion propagation in yeast cells. Here we describe the application of a new stochastic model that allows us to estimate more accurately the mean number of propagons in a [PSI+] cell. To achieve this accuracy we also experimentally determine key cell reproduction parameters and show that the presence of the [PSI+] prion has no impact on these key processes. Additionally, we experimentally determine the proportion of propagons transmitted to a daughter cell and show this reflects the relative cell volume of mother and daughter cells at cell division.While propagon generation is an ATP-driven process, the partition of propagons to daughter cells occurs by passive transfer via the distribution of cytoplasm. Furthermore, our new estimates of n(0), the number of propagons per cell (500-1000), are some five times higher than our previous estimates and this has important implications for our understanding of the inheritance of the [PSI+] and the spontaneous formation of prion-free cells