2,759 research outputs found

    Goal driven optimization of process parameters for maximum efficiency in laser bending of advanced high strength steels

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    Laser forming or bending is fast becoming an attractive option for the forming of advanced high strength steels (AHSS), due primarily to the reduced formability of AHSS when compared with conventional steels in traditional contact-based forming processes. An inherently iterative process, laser forming must be optimized for efficiency in order to compete with contact based forming processes; as such, a robust and accurate method of optimal process parameter prediction is required. In this paper, goal driven optimization is conducted, utilizing numerical simulations as the basis for the prediction of optimal process parameters for the laser bending of DP 1000 steel. A key consideration of the optimization process is the requirement for minimal microstructural transformation in automotive grade high strength steels such as DP 1000

    Oscillatory oblique stagnation-point flow toward a plane wall

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    Two-dimensional oscillatory oblique stagnation-point flow toward a plane wall is investigated. The problem is a eneralisation of the steady oblique stagnation-point flow examined by previous workers. Far from the wall, the flow is composed of an irrotational orthogonal stagnation-point flow with a time-periodic strength, a simple shear flow of constant vorticity, and a time-periodic uniform stream. An exact solution of the Navier-Stokes equations is sought for which the flow streamfunction depends linearly on the coordinate parallel to the wall. The problem formulation reduces to a coupled pair of partial differential equations in time and one spatial variable. The first equation describes the oscillatory orthogonal stagnation-point flow discussed by previous workers. The second equation, which couples to the first, describes the oblique component of the flow. A description of the flow velocity field, the instantaneous streamlines, and the particle paths is sought through numerical solutions of the governing equations and via asymptotic analysis

    Accessing novel fluorinated heterocycles with the hypervalent fluoroiodane reagent by solution and mechanochemical synthesis

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    A new and efficient strategy for the rapid formation of novel fluorinated tetrahydropyridazines and dihydrooxazines has been developed by fluorocylisation of β,γ-unsaturated hydrazones and oximes with the hypervalent fluoroiodane reagent. Mechanochemical synthesis delivered fluorinated tetrahydropyridazines in similar excellent yields to conventional solution synthesis, whereas fluorinated dihydro-oxazines were prepared in much better yields by ball-milling

    Selection Of A Novel Aptamer Against Vitronectin Using Capillary Electrophoresis And Next Generation Sequencing

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    Breast cancer (BC) results in ≃40,000 deaths each year in the United States and even among survivors treatment of the disease may have devastating consequences, including increased risk for heart disease and cognitive impairment resulting from the toxic effects of chemotherapy. Aptamer-mediated drug delivery can contribute to improved treatment outcomes through the selective delivery of chemotherapy to BC cells, provided suitable cancer-specific antigens can be identified. We report here the use of capillary electrophoresis in conjunction with next generation sequencing to develop the first vitronectin (VN) binding aptamer (VBA-01; Kd 405 nmol/l, the first aptamer to vitronectin (VN; Kd = 405 nmol/l), a protein that plays an important role in wound healing and that is present at elevated levels in BC tissue and in the blood of BC patients relative to the corresponding nonmalignant tissues. We used VBA-01 to develop DVBA-01, a dimeric aptamer complex, and conjugated doxorubicin (Dox) to DVBA-01 (7:1 ratio) using pH-sensitive, covalent linkages. Dox conjugation enhanced the thermal stability of the complex (60.2 versus 46.5°C) and did not decrease affinity for the VN target. The resulting DVBA-01-Dox complex displayed increased cytotoxicity to MDA-MB-231 BC cells that were cultured on plasticware coated with VN (1.8 × 10⁻⁶mol/l) relative to uncoated plates (2.4 × 10⁻⁶ mol/l), or plates coated with the related protein fibronectin (2.1 × 10⁻⁶ mol/l). The VBA-01 aptamer was evaluated for binding to human BC tissue using immunohistochemistry and displayed tissue specific binding and apparent association with BC cells. In contrast, a monoclonal antibody that preferentially binds to multimeric VN primarily stained extracellular matrix and vessel walls of BC tissue. Our results indicate a strong potential for using VN-targeting aptamers to improve drug delivery to treat BC

    Improving health and education outcomes for children in remote communities: A cross-sector and developmental evaluation approach

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    Early childhood is one of the most influential developmental life stages. Attainments at this stage will have implications for the quality of life children experience as they transition to adulthood. Children residing in remote Australia are exposed to socioeconomic disadvantage that can contribute to developmental delays and resultant poorer education and health outcomes. Complex contributing factors in far west New South Wales have resulted in children with speech and fine motor skill delays experiencing no to limited access to allied health services for a number of decades. More recently, growing awareness that no single policy, government agency, or program could effectively respond to these complexities or ensure appropriate allied health service access for children in these communities has led to the development of the Allied Health in Outback Schools Program, which has been operational since 2009. The program is underpinned by cross-sector partnerships and a shared aspirational aim to improve the developmental outcomes of children to enhance their later life opportunities. It was identified early that the initiative had the potential to deliver mutually beneficial outcomes for communities and participating partner organisations.Over the last five years the program has been the catalyst for partnership consolidation, expansion and diversification. The developmental evaluation approach to continuous program adaptation and refinement has provided valuable insights that have informed health and education policy and enabled the program to be responsive to changing community needs, emerging policy and funding reforms.This article explores the evolution of the program partnerships, their contribution to program success and longevity, and their capacity to respond to an emergent and dynamic environment. The authors propose that a community-centred and developmental approach to program innovation and implementation in remote locations is required. This is based on the premise that contemporary linear, logic-based policy development and funding allocations, with predetermined program deliverables and outcomes, are no longer capable of responding appropriately to the complexities experienced by remote communities.Keywords: allied health, remote communities, cross-sectoral partnerships, service learnin

    A population-based observational study on the factors associated with the completion of palliative chemotherapy among patients with oesophagogastric cancer.

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    OBJECTIVES: Palliative chemotherapy is routinely given to patients diagnosed with locally advanced or metastatic oesophagogastric (O-G) cancer. We examine which patients with O-G cancer in England receive palliative chemotherapy, and identify factors associated with treatment completion. DESIGN: A prospective population-based observational study. SETTING: All English National Health Service (NHS) trusts diagnosing patients with O-G cancer. PARTICIPANTS: Data were prospectively collected on patients diagnosed with invasive epithelial cancer of the oesophagus or stomach between 1 October 2007 and 30 June 2009 in English NHS hospitals, and those who had palliative treatment intent. OUTCOME MEASURE: We calculated the proportion of patients with different characteristics (eg, age, sex, stage at diagnosis, performance status) starting palliative chemotherapy. Multiple logistic regression was used to identify characteristics associated with non-completion of chemotherapy. RESULTS: There were 9768 patients in the study whose treatment intent was palliative. Among these, 2313 (24%) received palliative chemotherapy. It was received by 51% of patients aged under 55 years but only 9% of patients aged 75 years or over. Overall, 917 patients (53%) completed their treatment among the 1741 patients for whom information on treatment completion was recorded. Treatment completion ranged from 50-60% for patients with good performance status but was under 35% for patients aged 55 years or older with poor performance status. Treatment completion was not associated with site of cancer, pretreatment stage, sex, comorbidities or histology. CONCLUSIONS: Completion rates of palliative chemotherapy in patients with O-G cancer are low and elderly patients with poor performance status are very unlikely to complete a palliative chemotherapy treatment. Clinicians and patients should consider this information when balancing potential (survival) benefits, toxicity of treatment and its effect on quality of life

    Coding of Barrett's oesophagus with high-grade dysplasia in national administrative databases: a population-based cohort study.

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    OBJECTIVES: The International Classification of Diseases 10th Revision (ICD-10) system used in the English hospital administrative database (Hospital Episode Statistics (HES)) does not contain a specific code for oesophageal high-grade dysplasia (HGD). The aim of this paper was to examine how patients with HGD were coded in HES and whether it was done consistently. SETTING: National population-based cohort study of patients with newly diagnosed with HGD in England. The study used data collected prospectively as part of the National Oesophago-Gastric Cancer Audit (NOGCA). These records were linked to HES to investigate the pattern of ICD-10 codes recorded for these patients at the time of diagnosis. PARTICIPANTS: All patients with a new diagnosis of HGD between 1 April 2013 and 31 March 2014 in England, who had data submitted to the NOGCA. OUTCOMES MEASURED: The main outcome assessed was the pattern of primary and secondary ICD-10 diagnostic codes recorded in the HES records at endoscopy at the time of diagnosis of HGD. RESULTS: Among 452 patients with a new diagnosis of HGD between 1 April 2013 and 31 March 2014, Barrett's oesophagus was the only condition coded in 200 (44.2%) HES records. Records for 59 patients (13.1%) contained no oesophageal conditions. The remaining 193 patients had various diagnostic codes recorded, 93 included a diagnosis of Barrett's oesophagus and 57 included a diagnosis of oesophageal/gastric cardia cancer. CONCLUSIONS: HES is not suitable to support national studies looking at the management of HGD. This is one reason for the UK to adopt an extended ICD system (akin to ICD-10-CM)

    Flow in a slowly-tapering channel with oscillating walls

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    The flow of a fluid in a channel with walls inclined at an angle to each other is investigated at arbitrary Reynolds number. The flow is driven by an oscillatory motion of the wall incorporating a time-periodic displacement perpendicular to the channel centreline. The gap between the walls varies linearly with distance along the channel and is a prescribed periodic function of time. An approximate solution is constructed assuming that the angle of inclination of the walls is small. At leading order the flow corresponds to that in a channel with parallel, vertically oscillating walls examined by Hall and Papageorgiou \cite{HP}. A careful study of the governing partial differential system for the first order approximation controlling the tapering flow due to the wall inclination is conducted. It is found that as the Reynolds number is increased from zero the tapering flow loses symmetry and undergoes exponential growth in time. The loss of symmetry occurs at a lower Reynolds number than the symmetry-breaking for the parallel-wall flow. A window of asymmetric, time-periodic solutions is found at higher Reynolds number, and these are reached via a quasiperiodic transient from a given set of initial conditions. Beyond this window stability is again lost to exponentially growing solutions as the Reynolds number is increased

    Re-organisation of oesophago-gastric cancer care in England: progress and remaining challenges

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    RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Oesophago-gastric cancer services in England have been extensively reorganised since 2001 to deliver a centralised, specialist-led service. Our aim was to assess how well the National Health Service (NHS) in England met organisational standards for oesophago-gastric cancer care. Methods Questionnaires that asked about the provision of staging investigations, curative and palliative treatments and key personnel were sent in September 2007 to the lead clinician for oesophago-gastric cancer at all 30 cancer networks and 156 NHS acute trusts in England. Results Responses were received from all networks and 81% of NHS trusts. All networks provided essential staging investigations and a range of endoscopic palliative therapies. Only 16 of the 30 cancer networks discussed all patients at the specialist multi-disciplinary team meeting and 11 networks had not fully centralised curative surgery. There was also variation between NHS trusts in the integration of the palliative care team, the availability of nurse specialists and the use of dieticians to provide nutritional support. Conclusion There has been considerable progress in reforming oesophago-gastric cancer services but the process of reorganisation is still incomplete and regional differences in service provision exist that may lead to variation in patient outcomes.Published versio
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