7,353 research outputs found

    A ‘healthy baby’: The double imperative of preimplantation genetic diagnosis

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    This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 The Authors.This article reports from a study exploring the social processes, meanings and institutions that frame and produce ‘ethical problems’ and clinical dilemmas for practitioners, scientists and others working in the specialty of preimplantation genetic diagnosis (PGD). A major topic in the data was that, in contrast to IVF, the aim of PGD is to transfer to the woman’s womb only those embryos likely to be unaffected by serious genetic disorders; that is, to produce ‘healthy babies’. Staff described the complex processes through which embryos in each treatment cycle must meet a double imperative: they must be judged viable by embryologists and ‘unaffected’ by geneticists. In this article, we focus on some of the ethical, social and occupational issues for staff ensuing from PGD’s double imperative.The Wellcome Trus

    Decoherence in Josephson Qubits from Dielectric Loss

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    Dielectric loss from two-level states is shown to be a dominant decoherence source in superconducting quantum bits. Depending on the qubit design, dielectric loss from insulating materials or the tunnel junction can lead to short coherence times. We show that a variety of microwave and qubit measurements are well modeled by loss from resonant absorption of two-level defects. Our results demonstrate that this loss can be significantly reduced by using better dielectrics and fabricating junctions of small area 10μm2\lesssim 10 \mu \textrm{m}^2. With a redesigned phase qubit employing low-loss dielectrics, the energy relaxation rate has been improved by a factor of 20, opening up the possibility of multi-qubit gates and algorithms.Comment: shortened version submitted to PR

    Chlamydiae assemble a pathogen synapse to hijack the host endoplasmic reticulum

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    Chlamydiae are obligate intracellular bacterial pathogens that replicate within a specialised membrane-bound compartment, termed an ‘inclusion’. The inclusion membrane is a critical host-pathogen interface, yet the extent of its interaction with cellular organelles and the origin of this membrane remain poorly defined. Here we show that the host endoplasmic reticulum (ER) is specifically recruited to the inclusion, and that key rough ER (rER) proteins are enriched on and translocated into the inclusion. rER recruitment is a Chlamydia-orchestrated process that occurs independently of host trafficking. Generation of infectious progeny requires an intact ER, since ER vacuolation early during infection stalls inclusion development, whereas disruption post ER recruitment bursts the inclusion. Electron tomography and immunolabelling of Chlamydia-infected cells reveal ‘pathogen synapses’ at which ordered arrays of chlamydial type III secretion complexes connect to the inclusion membrane only at rER contact sites. Our data demonstrate a supramolecular assembly involved in pathogen hijack of a key host organelle

    Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during pseudomonas aeruginosa infection

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    Bacterial infection can trigger autophagy and inflammasome activation, but the effects of inflammasome activation on autophagy are unknown. We examined this in the context of Pseudomonas aeruginosa macrophage infection, which triggers NLRC4 inflammasome activation. P. aeruginosa induced autophagy via TLR4 and its adaptor TRIF. NLRC4 and caspase-1 activation following infection attenuated autophagy. Caspase-1 directly cleaved TRIF to diminish TRIF-mediated signaling, resulting in inhibition of autophagy and in reduced type I interferon production. Expression of a caspase-1 resistant TRIF mutant enhanced autophagy and type I interferon production following infection. Preventing TRIF cleavage by caspase-1 in an in vivo model of P. aeruginosa infection resulted in enhanced bacterial autophagy, attenuated IL-1β production, and increased bacterial clearance. Additionally, TRIF cleavage by caspase-1 diminished NLRP3 inflammasome activation. Thus, caspase-1 mediated TRIF cleavage is a key event in controlling autophagy, type I interferon production, and inflammasome activation with important functional consequences

    Communications Biophysics

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    Contains reports on six research projects.National Science Foundation (Grant G-16526)National Institutes of Health (Grant MH-04737-02

    The Adoption and Implementation of Evidence-Based Practice (EBP) Among Allied Health Professions.

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    Background and aims: Evidence-based practice (EBP) is widely accepted within patient care as it ensures health care professionals remain informed of recent evidence and research relating to their clinical practice. However, the particular characteristics detrimental to the successful implementation of EBP within Allied Health Professionals' (AHP) clinical practice are unknown. The purpose of this study was to assess and characterise adoption of EBP within AHP's clinical practice. Methods: Questionnaires comprising the Evidence-Based Practice Questionnaire (EBPQ; Upton and Upton, 2006a) were administered to 154 (response rate=27.3%) newly qualified practitioners (NQPs) from NHSScotland. Data were analysed to determine attitudes, knowledge and skill of EBP; K-means cluster and chi-square analyses were conducted in order to differentiate profiles of NPQs within high-, medium- and low- categories on the EBPQ practice and knowledge/skills sub-sections. Findings: Moderate scores were recorded for NQP's implementation, knowledge, and attitudes toward EBP. Chi-square analysis performed on the high-, moderate- and low- practice and skills' profiles revealed no significant results for NQP's year qualified, age, or year of clinical practice. Conclusions: The findings illustrate that the majority of NQPs have a good understanding of the application and importance of EPB, and suggests the improvement in NQPs training with regards to EBP enables them to successfully transfer acquired knowledge within their clinical practice

    Non-invasive diffusion tensor imaging detects white matter degeneration in the spinal cord of a mouse model of amyotrophic lateral sclerosis

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    Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. Here we examine the ability of magnetic resonance imaging (MRI) to measure axonal degeneration in the lumbar spinal cord of the SOD1 mouse model of ALS. Diffusion tensor imaging (DTI) was successful in detecting axonal spinal cord damage in vivo. Fractional anisotropy (FA) values were reduced exclusively in the ventral white matter tracts of the lumbar spinal cord of ALS-affected SOD1 mice compared to wild-type littermates, with this effect becoming more pronounced with disease progression. The reduced FA values were therefore limited to white matter tracts arising from the motor neurons, whereas sensory white matter fibers were preserved. Significant decreases in water diffusion parallel to the white matter fibers or axial diffusivity were observed in the SOD1 mice, which can be attributed to the axonal degeneration observed by electron microscopy. At the same time, radial diffusivity perpendicular to the spinal column increased in the SOD1 mice, reflecting reduced myelination. These results demonstrate the usefulness of MRI in tracking disease progression in live animals and will aid in the assessment of treatment efficacy. This method could also potentially be adapted to aid the diagnosis and assessment of ALS progression in humans. © 2010 Elsevier Inc. All rights reserved

    Studying changes in the practice of two teachers developing assessment for learning

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    This paper describes changes in the practice of two teachers, observed over an eighteen month period, who were participating in a study intended to support teachers in developing their use of assessment in support of learning. The design of the intervention allowed each teacher to choose for themselves which aspects of their practice to develop. Analysis of lesson observations, journal entries and interviews indicate that both teachers were keen to change their practice, but were concerned about the disruption to their established routines, and in particular about the potential for loss of control of their classes. Both teachers did effect significant changes in their classrooms, but these tended to be developments of existing preferred ways of working, rather than radical innovations. In conclusion, it is suggested that to be most effective, teacher professional development needs to be structured strongly enough to afford teacher growth, but flexible enough to allow different teachers to take their practice in different ways

    Integration of Neural Architecture within a Finite Element Framework for Improved Neuromusculoskeletal Modeling

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    Neuromusculoskeletal (NMS) models can aid in studying the impacts of the nervous and musculoskeletal systems on one another. These computational models facilitate studies investigating mechanisms and treatment of musculoskeletal and neurodegenerative conditions. In this study, we present a predictive NMS model that uses an embedded neural architecture within a finite element (FE) framework to simulate muscle activation. A previously developed neuromuscular model of a motor neuron was embedded into a simple FE musculoskeletal model. Input stimulation profiles from literature were simulated in the FE NMS model to verify effective integration of the software platforms. Motor unit recruitment and rate coding capabilities of the model were evaluated. The integrated model reproduced previously published output muscle forces with an average error of 0.0435 N. The integrated model effectively demonstrated motor unit recruitment and rate coding in the physiological range based upon motor unit discharge rates and muscle force output. The combined capability of a predictive NMS model within a FE framework can aid in improving our understanding of how the nervous and musculoskeletal systems work together. While this study focused on a simple FE application, the framework presented here easily accommodates increased complexity in the neuromuscular model, the FE simulation, or both
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