900 resultados para rigour and relevance


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In this paper I discuss David Shaw’s claim that the body of a terminally ill person can be conceived as a kind of life-support, akin to an artificial ventilator. I claim that this position rests upon an untenable dualism between the mind and the body. Given that dualism continues to be attractive to some thinkers, I attempt to diagnose the reasons why it continues to be attractive, as well as to demonstrate its incoherence, drawing on some recent work in the philosophy of psychology. I conclude that, if my criticisms are sound, Shaw’s attempt to deny the distinction between withdrawal and euthanasia fails.

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Particles emitted by vehicles are known to cause detrimental health effects, with their size and oxidative potential among the main factors responsible. Therefore, understanding the relationship between traffic composition and both the physical characteristics and oxidative potential of particles is critical. To contribute to the limited knowledge base in this area, we investigated this relationship in a 4.5 km road tunnel in Brisbane, Australia. On-road concentrations of ultrafine particles (<100 nm, UFPs), fine particles (PM2.5), CO, CO2 and particle associated reactive oxygen species (ROS) were measured using vehicle-based mobile sampling. UFPs were measured using a condensation particle counter and PM2.5 with a DustTrak aerosol photometer. A new profluorescent nitroxide probe, BPEAnit, was used to determine ROS levels. Comparative measurements were also performed on an above-ground road to assess the role of emission dilution on the parameters measured. The profile of UFP and PM2.5 concentration with distance through the tunnel was determined, and demonstrated relationships with both road gradient and tunnel ventilation. ROS levels in the tunnel were found to be high compared to an open road with similar traffic characteristics, which was attributed to the substantial difference in estimated emission dilution ratios on the two roadways. Principal component analysis (PCA) revealed that the levels of pollutants and ROS were generally better correlated with total traffic count, rather than the traffic composition (i.e. diesel and gasoline-powered vehicles). A possible reason for the lack of correlation with HDV, which has previously been shown to be strongly associated with UFPs especially, was the low absolute numbers encountered during the sampling. This may have made their contribution to in-tunnel pollution largely indistinguishable from the total vehicle volume. For ROS, the stronger association observed with HDV and gasoline vehicles when combined (total traffic count) compared to when considered individually may signal a role for the interaction of their emissions as a determinant of on-road ROS in this pilot study. If further validated, this should not be overlooked in studies of on- or near-road particle exposure and its potential health effects.

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The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.

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The purpose of this paper is to consider how libraries support the development of community networks both physically and digitally. To do this, a case-study methodology was employed, including a combination of data about the library and qualitative interviews with library users considering their experience of the library. This paper proposes that libraries act as ‘third places’ spatially connecting people; libraries also build links with online media and play a critical role in inclusively connecting non-technology users with the information on the Internet and digital technology more generally. The paper establishes the value of libraries in the digital age and recommends that libraries actively seek ways to develop links between non-technology users and activity on the Internet. It addresses the need to reach these types of non-technology users in different ways. Further, it suggests that libraries utilise their positioning as third places to create broader community networks, to support local communities beyond existing users and beyond the library precinct.

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This paper provides an overview of the regulatory developments in the UK which impact on the use of in vitro fertilization (IVF) and embryo screening techniques for the creation of “saviour siblings.” Prior to the changes implemented under the Human Fertilisation and Embryology Act 2008, this specific use of IVF was not addressed by the legislative framework and regulated only by way of policy issued by the Human Fertilisation and Embryology Authority (HFEA). Following the implementation of the statutory reforms, a number of restrictive conditions are now imposed on the face of the legislation. This paper considers whether there is any justification for restricting access to IVF and pre-implantation tissue typing for the creation of “saviour siblings.” The analysis is undertaken by examining the normative factors that have guided the development of the UK regulatory approach prior to the 2008 legislative reforms. The approach adopted in relation to the “saviour sibling” issue is compared to more general HFEA policy, which has prioritized the notion of reproductive choice and determined that restrictions on access are only justified on the basis of harm considerations.

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As buildings have become more advanced and complex, our ability to understand how they are operated and managed has diminished. Modern technologies have given us systems to look after us but it appears to have taken away our say in how we like our environment to be managed. The aim of this paper is to discuss our research concerning spaces that are sensitive to changing needs and allow building-users to have a certain level of freedom to understand and control their environment. We discuss why, what we call the Active Layer, is needed in modern buildings; how building inhabitants are to interact with it; and the development of interface prototypes to test consequences of having the Active Layer in our environment.

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The inhibiting effect of COads on platinum-based anodes is a major problem in the development of ambient temperature, polyelectrolyte membrane-type fuel cells. One of the unusual features of the response for the oxidative removal of the species in question is that the response observed for this reaction in the positive sweep is highly dependent on the CO admission potential, for example, when the COads is formed in the Hads region it undergoes oxidation at unusually low potentials. Such behaviour is attributed here to hydrogen activation of the platinum surface, with the result that oxide mediators (and COads oxidation) occurs at an earlier stage of the positive sweep. It is also demonstrated, for both platinum and gold in acid solution, that dramatic premonolayer oxidation responses may be observed following suitable preactivation of the electrode surfaces. It is suggested that the defect state of a solid electrode surface is an important variable whose investigation may yield improved fuel cell anode performance.

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This thesis documented pathogenic species of nontuberculous mycobacteria in the Brisbane water distribution system. When water and shower aerosol strains were compared with human strains of mycobacteria, the study found that the likelihood of acquiring infection from municipal water was specific for four main species. The method for isolation of mycobacteria from water was refined, followed by sampling from 220 sites across Brisbane. A variety of species (incl 15 pathogens) were identified and genotypically compared to human strains. For M. abscessus and M. lentiflavum, water strains clustered with human strains. Pathogenic strains of M. kansasii were found, though non-pathogenic strains dominated. Waterborne strains of M. fortuitum differed to human strains. Extensive home sampling of 20 patients with NTM disease, supported the theory that the risk of acquiring NTM from water or shower aerosols appears species specific for M. avium, M. kansasii, M. lentiflavum and M. abscessus.

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In a people-to-people matching systems, filtering is widely applied to find the most suitable matches. The results returned are either too many or only a few when the search is generic or specific respectively. The use of a sophisticated recommendation approach becomes necessary. Traditionally, the object of recommendation is the item which is inanimate. In online dating systems, reciprocal recommendation is required to suggest a partner only when the user and the recommended candidate both are satisfied. In this paper, an innovative reciprocal collaborative method is developed based on the idea of similarity and common neighbors, utilizing the information of relevance feedback and feature importance. Extensive experiments are carried out using data gathered from a real online dating service. Compared to benchmarking methods, our results show the proposed method can achieve noticeable better performance.

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Non-small cell lung carcinoma remains by far the leading cause of cancer-related deaths worldwide. Overexpression of FLIP, which blocks the extrinsic apoptotic pathway by inhibiting caspase-8 activation, has been identified in various cancers. We investigated FLIP and procaspase-8 expression in NSCLC and the effect of HDAC inhibitors on FLIP expression, activation of caspase-8 and drug resistance in NSCLC and normal lung cell line models. Immunohistochemical analysis of cytoplasmic and nuclear FLIP and procaspase-8 protein expression was carried out using a novel digital pathology approach. Both FLIP and procaspase-8 were found to be significantly overexpressed in tumours, and importantly, high cytoplasmic expression of FLIP significantly correlated with shorter overall survival. Treatment with HDAC inhibitors targeting HDAC1-3 downregulated FLIP expression predominantly via post-transcriptional mechanisms, and this resulted in death receptor- and caspase-8-dependent apoptosis in NSCLC cells, but not normal lung cells. In addition, HDAC inhibitors synergized with TRAIL and cisplatin in NSCLC cells in a FLIP- and caspase-8-dependent manner. Thus, FLIP and procaspase-8 are overexpressed in NSCLC, and high cytoplasmic FLIP expression is indicative of poor prognosis. Targeting high FLIP expression using HDAC1-3 selective inhibitors such as entinostat to exploit high procaspase-8 expression in NSCLC has promising therapeutic potential, particularly when used in combination with TRAIL receptor-targeted agents.

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A significant reduction in global greenhouse gas (GHG) emissions is a priority, and the preservation of existing building stock presents a significant opportunity to reduce the carbon footprint of our built environment. Within this ‘wicked’ problem context, and moving beyond the ad hoc and incremental performance improvements that have been made to date, collaborative and multidisciplinary efforts are required to find rapid and transformational solutions. Design has emerged as a strategic and redirective practice, and lessons can therefore be learned about transformation and potentially applied in the built environment. The purpose of this paper is to discuss a pragmatic and novel research approach for undertaking such applied design driven research. This paper begins with a discussion of key contributions from design science (rational) and action research (reflective) philosophies in creating an emerging methodological ‘hybrid design approach’. This research approach is then discussed in relation to its application to specific research exploring the processes, methods and lessons from design in heritage building retrofit projects. Drawing on both industry and academic knowledge to ensure relevance and rigour, it is anticipated that the hybrid design approach will be useful for others tackling such complex wicked problems that require context-specific solutions.

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This study presents an acoustic emission (AE) based fault diagnosis for low speed bearing using multi-class relevance vector machine (RVM). A low speed test rig was developed to simulate the various defects with shaft speeds as low as 10 rpm under several loading conditions. The data was acquired using anAEsensor with the test bearing operating at a constant loading (5 kN) andwith a speed range from20 to 80 rpm. This study is aimed at finding a reliable method/tool for low speed machines fault diagnosis based on AE signal. In the present study, component analysis was performed to extract the bearing feature and to reduce the dimensionality of original data feature. The result shows that multi-class RVM offers a promising approach for fault diagnosis of low speed machines.

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JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS-2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non-neoplastic tissues) using real-time polymerase chain reaction. JS-2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS-2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression levels for JS-2 mRNA between different colorectal tissues were noted (p = 0.05). Distal colorectal adenocarcinoma had significantly higher copy number than proximal adenocarcinoma (p = 0.005). The relative expression level of JS-2 was different between colonic and rectal adenocarcinoma (p = 0.007). Mucinous adenocarcinoma showed higher JS-2 expression than non-mucinous adenocarcinoma (p = 0.02). Early T-stage cancers appear to have higher JS-2 copy number and lower expression of JS-2 mRNA than later stage cancers (p = 0.001 and 0.03 respectively). Colorectal cancer cell lines showed lower expression of JS-2 than the benign colorectal cell line. JS-2 copy number change and expression were shown for the first time to be altered in the carcinogenesis of colorectal cancer. In addition, genetic alteration of JS-2 was found to be related to location, pathological subtypes and staging of colorectal cancer.

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"For myself, I am an optimist - it does not seem to be much use to be anything else". Winston Churchill Optimism has its modern roots in philosophy dating back to the 17th century in the writings of philosophers such as Descartes and Voltaire (Domino & Conway, 2001). Previous to these philosophical writings, the concept of optimism was revealed in the teaching of many of the great spiritual traditions such as Buddhism and Christianity (Miller, Richards, & Keller, 2001). In the 20th century, optimism became defined in juxtaposition to pessimism, sometimes conceptualized as a bipolar unidimensional construct and by others as two related but separate constructs (Garber, 2000). Contemporary models (Scheier & Carver, 1985; Seligman, 1991) have increasingly focused on distinguishing optimism-pessimism as a general dispositional orientation, as described by expectancy theory, and as an explanatory process, described by explanatory style theory.