168 research outputs found

    Deaf Sign Language users and Audiology Services: a scoping review on cultural competence:INPLASY Protocol

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    Studies towards the total synthesis of Disorazole C1 and its analogues

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    Structure–activity relationships (SARs) in the disorazole family have been revealed through the biological testing of natural disorazoles and their synthetic analogues, but little is known about the contribution of the oxazole to the anti-tubulin activity of disorazole C1 I. The development of a novel Evans–Tishchenko/alkyne metathesis (ET–AM) route towards the synthesis of disorazole C1 will provide straightforward access to disorazole C1 and its heterocyclic analogues, thus allowing the contribution of the oxazole to the natural product’s bioactivity to be elucidated. Our ET–AM approach offers a highly diastereoselective and convergent means of constructing heterocyclic analogues of the disorazole C1 scaffold Het-II. It is envisaged that ET coupling of C(1)–C(9) aldehydes Het-IV to the C(10)–C(19) β-hydroxyketone V will give the key, requisite, 1,3-anti diol monoester bis-alkynes Het-III for dimerisation via an alkyne cross-metathesis/ring-closing alkyne metathesis (ACM–RCAM) reaction. Further diversification may be achieved through the synthesis of C(6)-heteroatom analogues of the C(1)–C(9) fragment Het-IV. Chapter 2 outlines efforts towards the synthesis of C(6)-amino analogues Het-VI of the C(1)–C(9) fragment IV. Elaboration of Garner’s aldehyde VIII allowed the synthesis of the N-protected C(5)–C(9) mesylate VII; an analogue of an advanced C(1)–C(9) fragment intermediate. A scalable route towards the synthesis of the C(10)–C(19) fragment V and investigations into its reactivity under ET coupling conditions are critical to the success of our ET–AM approach. Chapter 3 details convergent approaches towards the synthesis of the C(10)–C(19) β-hydroxyketone V, which centred around: (i) an olefin cross-metathesis reaction [C(11)–C(12) disconnection]; (ii) an epoxide ringopening reaction [C(12)–C(13) disconnection]; and (iii) a Mukaiyama aldol reaction [C(14)–C(15) disconnection]. Chapter 4 describes our successful linear synthesis of the β-hydroxyketone V. Gram-scale preparation of the C(10)–C(19) fragment V permitted investigation into the viability of the ET reaction as a fragment coupling strategy, the results of which are reported in Chapter 5. Although many (hetero)aryl aldehydes failed to react, the successful coupling of electron-deficient substrates allowed a contingency strategy to be explored through preparation of the mono-protected diol IX. Esterification of IX with the carboxylic acid derivative of the C(1)–C(9) oxazole has allowed generation of the C(1)–C(9)/C(10')–C(19') bis-alkyne X required for future AM investigations

    The effects of driver fatigue, gender, and distracted driving on perceived and observed aggressive driving behavior: A correlated grouped random parameters bivariate probit approach.

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    Previous research has shown that the determinants of perceived and observed aggressive driving behavior may differ. However, the consideration of major sources of aggressive patterns may introduce additional variations in the effect of such determinants. This study aims to provide further insights in the variations of these two behavioral components arising from driver’s fatigue, gender as well as internal and external distractions (such as, rushing to destination, listening to music and solving logical problems) during the driving task. To identify how the factors determining perceived and observed aggressive behavior may vary across groups of drivers associated with such sources of aggressive driving, survey and simulation data are statistically analyzed. Separate models of perceived and observed aggressive driving behavior are estimated for fatigued and non-fatigued, distracted and non-distracted, male and female drivers. To address various aspects of unobserved heterogeneity, associated with the unobserved variations that are commonly shared among the behavioral components and participants, as well as their unobserved interactions, the correlated grouped random parameters bivariate probit modeling framework is employed. The results of the empirical analysis showed that the effect of the socio-demographic and behavioral factors on perceived and aggressive driving behavior may vary across the aforementioned groups of drivers, in terms of magnitude and directional effect. In addition, the identification of correlation among the unobserved characteristics further illustrates the complexities of the driving decision mechanism, especially when fundamental sources of aggressive driving are evident

    Experiential Learning in Vehicle Dynamics Education via Motion Simulation and Interactive Gaming

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    Creating active, student-centered learning situations in postsecondary education is an ongoing challenge for engineering educators. Contemporary students familiar with visually engaging and fast-paced games can find traditional classroom methods of lecture and guided laboratory experiments limiting. This paper presents a methodology that incorporates driving simulation, motion simulation, and educational practices into an engaging, gaming-inspired simulation framework for a vehicle dynamics curriculum. The approach is designed to promote active student participation in authentic engineering experiences that enhance learning about road vehicle dynamics. The paper presents the student use of physical simulation and large-scale visualization to discover the impact that design decisions have on vehicle design using a gaming interface. The approach is evaluated using two experiments incorporated into a sequence of two upper level mechanical engineering courses

    Research on the impact of the School Improvement Partnership Programme: Interim Report

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    In November 2013 Education Scotland commissioned the Robert Owen Centre for Education Change at The University of Glasgow to evaluate and support the School Improvement Partnership Programme (SIPP) for the first year of its implementation. The overall objectives for the evaluation support for SIPP were as follows: • To provide tailored support to up to 10 individual partnership projects which are part of the SIPP; • To assess how well the overall SIPP, and each individual partnership project within it, have been initiated; • To assess the extent to which the SIPP has contributed to its intended intermediate outcome; and • To make recommendations for the future development and potential scale-up of the SIP

    The Flying Car – Challenges and Strategies towards Future Adoption

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    In recent years, our surface transportation infrastructure is suffering from overuse, extreme traffic congestion, and roadway disrepair. Instead of following the traditional infrastructure expansion policy, current transportation research focuses on developing innovative and novel solutions to the aforementioned issues. Current pathways to overcoming these issues include the gradual transition towards a number of emerging transportation technologies, such as, autonomous motor vehicles for human transport, as well as unmanned aerial vehicles (UAV’s) and "drone" technologies for surveillance, and package deliveries. However, as a long-term solution, transportation scientists are also investigating the once-seemingly futuristic notion of flying car technology - a convergent form of ground/air vehicle transportation, and assessing associated regulations. In this paper, an extensive review of current literature is conducted to explore the technological capabilities of flying cars – each requiring appropriate regulations and governance – to become fully sustainable. Specifically, issues pertinent to training, safety, environment, navigation, infrastructure, logistics/sustainability, and cybersecurity and human factors are explored. This paper concludes with a preliminary quantitative analysis exploring the public perceptions associated with flying cars – including anticipated benefits, concerns, and willingness to both hire and acquire the technology once available to consumers. Insights offered by this data will help inform next-generation policies and standards associated with the gradual advancement of flying cars

    The Up-Scale Manufacture of Chondrocytes for Allogeneic Cartilage Therapies

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    Background: Allogeneic chondrocyte therapies need to be developed to allow more individuals to be treated with a cell therapy for cartilage repair and to reduce the burden and cost of current two-stage autologous procedures. Up-scale manufacture of chondrocytes using a bioreactor could help provide an off-the-shelf allogeneic chondrocyte therapy with many doses being produced in a single manufacturing run. Here we assess a Good Manufacturing Practice compliant hollow-fibre bioreactor (Quantum®) for adult chondrocyte manufacture. Methods: Chondrocytes were isolated from knee arthroplasty derived cartilage (n=5) and expanded in media supplemented with 10% fetal bovine serum (FBS) or 5% human platelet lysate (hPL) on tissue culture plastic (TCP) for a single passage. hPL supplemented cultures were then expanded in the Quantum® bioreactor for a further passage. Matched, parallel cultures in hPL or FBS were maintained on TCP. Chondrocytes from all culture conditions were characterised in terms of growth kinetics, morphology, immunoprofile, chondrogenic potential (chondrocyte pellet assays) and single telomere length analysis. Results: Quantum® expansion of chondrocytes resulted in 86.4±38.5x106 cells in 8.4±1.5 days, following seeding of 10.2±3.6 x106 cells. This related to 3.0±1.0 population doublings in the Quantum® bioreactor, compared with 2.1±0.6 and 1.3±1.0 on TCP in hPL and FBS supplemented media, respectively. Quantum® and TCP expanded cultures retained equivalent chondropotency and mesenchymal stromal cell markers immunoprofiles, with only integrin marker, CD49a, decreasing following Quantum® expansion. Quantum® expanded chondrocytes demonstrated equivalent chondrogenic potential (as assessed by ability to form and maintain chondrogenic pellets) with matched hPL TCP populations. hPL manufacture however, led to reduced chondrogenic potential and increased cell surface positivity of integrins CD49b, CD49c and CD51/61 compared with FBS cultures. Quantum® expansion of chondrocytes did not result in shortened 17p telomere length when compared with matched TCP cultures. Discussion: This study demonstrates that large numbers of adult chondrocytes can be manufactured in the Quantum® hollow-fibre bioreactor. This rapid, up-scale expansion, does not alter chondrocyte phenotype when compared with matched TCP expansion. Therefore, the Quantum® provides an attractive method of manufacturing chondrocytes for clinical use. Media supplementation with hPL for chondrocyte expansion may, however, be unfavourable in terms of retaining chondrogenic capacity

    Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study.

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    PURPOSE: Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients. METHODS: Multi-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (Tregs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections. RESULTS: A total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of Tregs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00-4.74), 3.44 (1.58-7.47) and 2.41 (1.14-5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9. CONCLUSIONS: This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT02186522).The study was funded by Innovate UK (Sepsis 2: 101193), BD Biosciences and the National Institute for Academic Anaesthesia. Dr Conway Morris is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z). Dr Shankar-Hari is supported by the National Institute for Health Research Clinician Scientist Award (CS-2016-16- 011)
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