1,941 research outputs found

    Design of elastomer coatings for concrete impact damage mitigation

    Get PDF
    Practical, cost-effective strategies are of interest for the protection of vulnerable infrastructure against dynamic load events such as blast and fragment impact. Recent research has established that spray-on elastomer coatings can provide a significant impact mitigating effect when applied to concrete structural elements [1]. However, to date, no practical design guidelines exist to support efficient implementation of this retrofit solution. In this work, an analytical model is proposed for the impact indentation of an elastomer-coated concrete structural element. Design maps are produced, predicting the critical projectile impact velocities for elastomer failure and concrete failure, taking the coating thickness and elastomer modulus as the key design variables. The analytical predictions provide a close match to experimental and finite element analysis (FEA) results [1,2]. Spanning a realistic range of elastomer moduli, representative of typical spray application polymers, a regime change is predicted that depends only on the elastomer modulus, Ee. For Ee &lt; 50 MPa, elastomer failure is predicted to occur first. In this regime, there is a much higher sensitivity to Ee compared with the elastomer thickness, he. For Ee &gt; 50 MPa, the concrete is predicted to fail first and in this regime, the critical velocities are most sensitive to he compared with Ee.</p

    Plate-impact loading of cellular structures formed by selective laser melting

    No full text
    Porous materials are of great interest because of improved energy absorption over their solid counterparts. Their properties, however, have been difficult to optimize. Additive manufacturing has emerged as a potential technique to closely define the structure and properties of porous components, i.e. density, strut width and pore size; however, the behaviour of these materials at very high impact energies remains largely unexplored. We describe an initial study of the dynamic compression response of lattice materials fabricated through additive manufacturing. Lattices consisting of an array of intersecting stainless steel rods were fabricated into discs using selective laser melting. The resulting discs were impacted against solid stainless steel targets at velocities ranging from 300 to 700 m s-1 using a gas gun. Continuum CTH simulations were performed to identify key features in the measured wave profiles, while 3D simulations, in which the individual cells were modelled, revealed details of microscale deformation during collapse of the lattice structure. The validated computer models have been used to provide an understanding of the deformation processes in the cellular samples. The study supports the optimization of cellular structures for application as energy absorbers. © 2014 IOP Publishing Ltd

    Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in mycobacterium tuberculosis–infected individuals

    Get PDF
    Copyright © 2009 by the American Thoracic Society.Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC

    Criteria for the use of omics-based predictors in clinical trials.

    Get PDF
    The US National Cancer Institute (NCI), in collaboration with scientists representing multiple areas of expertise relevant to 'omics'-based test development, has developed a checklist of criteria that can be used to determine the readiness of omics-based tests for guiding patient care in clinical trials. The checklist criteria cover issues relating to specimens, assays, mathematical modelling, clinical trial design, and ethical, legal and regulatory aspects. Funding bodies and journals are encouraged to consider the checklist, which they may find useful for assessing study quality and evidence strength. The checklist will be used to evaluate proposals for NCI-sponsored clinical trials in which omics tests will be used to guide therapy

    By design : negotiating flexible learning in the built environment discipline

    Full text link
    The term &lsquo;flexible education&rsquo; is now firmly entrenched within Australian higher education discourse, yet the term is a contested one imbued with a multiplicity of meanings. This paper describes a process designed to elucidate how the idea of flexible education can be translated into teaching models that are informed by the specific demands of disciplinary contexts. The process uses a flexible learning &lsquo;matching&rsquo; tool to articulate the understandings and preferences of students and academics of the Built Environment to bridge the gap between student expectations of flexibility and their teacher&rsquo;s willingness and ability to provide that flexibility within the limits of the pedagogical context and teaching resources. The findings suggest an informed starting point for educators in the Built Environment and other creative disciplines from which to traverse the complexities inherent in negotiating flexibility in an increasingly digital world

    Displaced but not replaced: the impact of e-learning on academic identities in higher education.

    Get PDF
    Challenges facing universities are leading many to implement institutional strategies to incorporate e-learning rather than leaving its adoption up to enthusiastic individuals. Although there is growing understanding about the impact of e-learning on the student experience, there is less understanding of academics’ perceptions of e-learning and its impact on their identities. This paper explores the changing nature of academic identities revealed through case study research into the implementation of e-learning at one UK university. By providing insight into the lived experiences of academics in a university in which technology is not only transforming access to knowledge but also influencing the balance of power between academic and student in knowledge production and use, it is suggested that academics may experience a jolt to their ‘trajectory of self’ when engaging with e-learning. The potential for e-learning to prompt loss of teacher presence and displacement as knowledge expert may appear to undermine the ontological security of their academic identity

    GNAO1 encephalopathy: broadening the phenotype and evaluating treatment and outcome

    Get PDF
    OBJECTIVE: To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1-related disease. METHODS: We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. RESULTS: Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. CONCLUSIONS: Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia

    User-made immobilities: a transitions perspective

    Get PDF
    In this paper we aim to conceptualize the role of users in creating, expanding and stabilizing the automobility system. Drawing on transition studies we offer a typology of user roles including user-producers, user-legitimators, user-intermediaries, user-citizens and user-consumers, and explore it on the historical transition to the automobile regime in the USA. We find that users play an important role during the entire transition process, but some roles are more salient than others in particular phases. Another finding is that the success of the transition depends on the stabilization of the emerging regime that will trigger upscaling in terms of the numbers of adopters. The findings are used to reflect on potential crossovers between transitions and mobilities research

    Now or never: perceptions of uniqueness induce acceptance of price increases for experiences more than for objects

    Get PDF
    Seven studies test and support the prediction that consumers are more willing to accept a price increase for an experiential versus a material purchase; an effect explained by the greater uniqueness of experiences. Critically, the uniqueness model advanced here is found to be independent of the happiness consumers derive from the purchase. To gain a deeper understanding of the uniqueness mechanism, this investigation then advances and tests a four-facet framework of uniqueness (unique opportunity, unique purchase, unique identity, and counterconformity). Together, the findings converge on the conclusion that consumers perceive the opportunity to have a particular experience (vs. object) as more unique, and this unique opportunity increases their willingness to accept a price increase. Overall, this work extends the experiential versus material purchases literature into a new domain—that of pricing; identifies the dimension—uniqueness—and its precise facet responsible for the effect—unique opportunity; and demonstrates that this model unfolds in a pattern distinct from the oft researched model centered on consumer happiness. Theoretical and practical implications are discussed.info:eu-repo/semantics/acceptedVersio

    HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

    Get PDF
    Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC
    corecore