Above | Below | Between

Thesis (Master's)--University of Washington, 2016-06

In vivo gene expression: DNA electrotransfer

The use of electric pulses to deliver therapeutic molecules to tissues and organs in vivo is a rapidly growing field of research. Electrotransfer can be used to deliver a wide range of potentially therapeutic agents, including drugs, proteins, oligonucleotides, RNA and DNA. Optimization of this approach depends upon a number of parameters such as target organ accessibility, cell turnover, microelectrode design, electric pulsing protocols and the physiological response to the therapeutic agent. Many organs have been successfully transfected by electroporation, including skin, liver, skeletal and cardiac muscle, male and female germ cells, artery, gut, kidney, retinal ganglion cells, cornea, spinal cord, joint synovium and brain. Electrotransfer technology is relevant in a variety of research and clinical settings including cancer therapy, modulation of pathogenic immune reactions, delivery of therapeutic proteins and drugs, and the identification of drug targets by the modulation of normal gene expression. This, together with the capacity to deliver very large DNA constructs, greatly expands the research and clinical applications of in vivo DNA electrotransfer.

Influences on doctors' prescribing: Is geographical remoteness a factor?

Objective: To identify factors influencing the prescribing of medicines by general practitioners in rural and remote Australia. Design: A qualitative study using a questionnaire to determine attitudes about prescribing, specific prescribing habits and comments on prescribing in ‘rural practice’. Setting: General practice in rural and remote Queensland. Subjects: General practitioners practising in rural and remote settings in Queensland (n = 258). Main outcome measures: The factors perceived to influence the prescribing of medicines by medical practitioners in rural environments. Results: A 58% response rate (n = 142) was achieved. Most respondents agreed that they prescribe differently in rural compared with city practice. The majority of respondents agreed that their prescribing was influenced by practice location, isolation of patient home location, limited diagnostic testing and increased drug monitoring. Location issues and other issues were more likely to be identified as ‘influential’ by the more isolated practitioners. Factors such as access to continuing medical education and specialists were confirmed as having an influence on prescribing. The prescribing of recently marketed drugs was more likely by doctors practising in less remote rural areas. Conclusion: Practising in rural and remote locations is perceived to have an effect on prescribing. These influences need to be considered when developing quality use of medicines policies and initiatives for these locations. What is already known: Anecdotal and audit based studies have shown that rural general practice differs to urban-based practice in Australia, including some limited data showing some variations in prescribing patterns. No substantiated explanations for these variations have been offered. It is known that interventions to change prescribing behaviour are more likely to be effective if they are perceived as relevant and hence increasing our knowledge of rural doctors’ perceptions of differences in rural practice prescribing is required. What this study adds: Rural doctors believed that they prescribe differently in rural compared with city practice and they described a range of influences. The more remotely located doctors were more likely to report the ‘rural’ influences on prescribing, however, most results failed to reach statistical significance when compared to the less remotely located doctors. These perceptions should be considered when developing medicines policy and education for rural medical practitioners to ensure it is perceived rurally relevant.

Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD)

Aims The study estimated serious adverse event (SAE) rates among entrants to pharmacotherapies for opioid dependence, during treatment and after leaving treatment. Design A longitudinal study based on data from 12 trials included in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Participants and settings A total of 1.244 heroin users and methadone patients treated in hospital, community and GP settings. Intervention Six trials included detoxification; all included treatment with methadone, buprenorphine, levo-alpha-acetyl-methadol (LAAM) or naltrexone. Findings During 394 person-years of observation, 79 SAEs of 28 types were recorded. Naltrexone participants experienced 39 overdoses per 100 person-years after leaving treatment (44% occurred within 2 weeks after stopping naltrexone). This was eight times the rate recorded among participants who left agonist treatment. Rates of all other SAEs were similar during treatment versus out of treatment, for both naltrexone-treated and agonist-treated participants. Five deaths occurred, all among participants who had left treatment, at a rate of six per 100 person-years. Total SAE rates during naltrexone and agonist treatments were similar (20, 14 per 100 person-years, respectively). Total SAE and death rates observed among participants who had left treatment were three and 19 times the corresponding rates during treatment. Conclusions Individuals who leave pharmacotherapies for opioid dependence experience higher overdose and death rates compared with those in treatment. This may be due partly to a participant self-selection effect rather than entirely to pharmacotherapy being protective. Clinicians should alert naltrexone treatment patients in particular about heroin overdose risks. Duty of care may extend beyond cessation of dosing.

Prediction of protein B-factor profiles

The polypeptide backbones and side chains of proteins are constantly moving due to thermal motion and the kinetic energy of the atoms. The B-factors of protein crystal structures reflect the fluctuation of atoms about their average positions and provide important information about protein dynamics. Computational approaches to predict thermal motion are useful for analyzing the dynamic properties of proteins with unknown structures. In this article, we utilize a novel support vector regression (SVR) approach to predict the B-factor distribution (B-factor profile) of a protein from its sequence. We explore schemes for encoding sequences and various settings for the parameters used in SVR. Based on a large dataset of high-resolution proteins, our method predicts the B-factor distribution with a Pearson correlation coefficient (CC) of 0.53. In addition, our method predicts the B-factor profile with a CC of at least 0.56 for more than half of the proteins. Our method also performs well for classifying residues (rigid vs. flexible). For almost all predicted B-factor thresholds, prediction accuracies (percent of correctly predicted residues) are greater than 70%. These results exceed the best results of other sequence-based prediction methods. (C) 2005 Wiley-Liss, Inc.

Committee report: Guidelines for human startle eyeblink electromyographic studies

The human startle response is a sensitive, noninvasive measure of central nervous system activity that is Currently used in a wide variety of research and clinical settings. In this article, we raise methodological issues and present recommendations for optimal methods of startle blink electromyographic (EMG) response elicitation, recording, quantification, and reporting. It is hoped that this report Will foster more methodological validity and reliability in research using the startle response, Lis well Lis increase the detail with which relevant methodology is reported in publications using this measure.

Ecological validity in neuropsychological assessment: A case for greater consideration in research with neurologically intact populations

The focus of the discipline of neuropsychology is shifting towards a greater emphasis on understanding the relationship between assessment results and performance of everyday tasks (ecological validity). To date, the literature has highlighted the importance of this concept in the assessment of patients with brain injury or disease (e.g. in rehabilitation and forensic settings). This paper presents the argument that there is another important area in which the ecological validity of neuropsychological assessments should be considered: in clinical outcomes studies using neurologically intact participants. For example, determining the extent to which a medical procedure or intervention affects performance of everyday cognitive tasks can provide useful information that can potentially guide decision-making regarding treatment options. It is argued that tests designed with ecological validity in mind (the verisimilitude approach), as opposed to traditional tests, may be most effective at predicting everyday functioning. Explanations are proposed as to why researchers may be reluctant to use tests with verisimilitude in favor of more traditional measures. (c) 2006 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved.

The impact of supply chain performance measurement systems on dynamic behaviour in supply chains

The amplification of demand variation up a supply chain widely termed ‘the Bullwhip Effect’ is disruptive, costly and something that supply chain management generally seeks to minimise. Originally attributed to poor system design; deficiencies in policies, organisation structure and delays in material and information flow all lead to sub-optimal reorder point calculation. It has since been attributed to exogenous random factors such as: uncertainties in demand, supply and distribution lead time but these causes are not exclusive as academic and operational studies since have shown that orders and/or inventories can exhibit significant variability even if customer demand and lead time are deterministic. This increase in the range of possible causes of dynamic behaviour indicates that our understanding of the phenomenon is far from complete. One possible, yet previously unexplored, factor that may influence dynamic behaviour in supply chains is the application and operation of supply chain performance measures. Organisations monitoring and responding to their adopted key performance metrics will make operational changes and this action may influence the level of dynamics within the supply chain, possibly degrading the performance of the very system they were intended to measure. In order to explore this a plausible abstraction of the operational responses to the Supply Chain Council’s SCOR® (Supply Chain Operations Reference) model was incorporated into a classic Beer Game distribution representation, using the dynamic discrete event simulation software Simul8. During the simulation the five SCOR Supply Chain Performance Attributes: Reliability, Responsiveness, Flexibility, Cost and Utilisation were continuously monitored and compared to established targets. Operational adjustments to the; reorder point, transportation modes and production capacity (where appropriate) for three independent supply chain roles were made and the degree of dynamic behaviour in the Supply Chain measured, using the ratio of the standard deviation of upstream demand relative to the standard deviation of the downstream demand. Factors employed to build the detailed model include: variable retail demand, order transmission, transportation delays, production delays, capacity constraints demand multipliers and demand averaging periods. Five dimensions of supply chain performance were monitored independently in three autonomous supply chain roles and operational settings adjusted accordingly. Uniqueness of this research stems from the application of the five SCOR performance attributes with modelled operational responses in a dynamic discrete event simulation model. This project makes its primary contribution to knowledge by measuring the impact, on supply chain dynamics, of applying a representative performance measurement system.

Towards a pedagogical stylistics

Since the 1950s, pedagogical stylistics has been intrinsically linked with the teaching of written texts (and especially literary texts) to speakers of English as a second language. This is despite the fact that for decades many teachers have also structured their lessons in L1 classrooms to focus upon the linguistic features of literary texts as a means of enhancing their students’ understanding of literature and language. Recognizing that instructors in both L1 and L2 settings were often employing related pedagogical techniques without realizing that their colleagues in the other context were facing similar challenges, the PEDSIG group of the Poetics and Linguistics Association (PALA) has sought to add a theoretical dimension to research undertaken into practice in the stylistics classroom. Its goals, then, were: to establish a working definition of pedagogical stylistics; to identify the theoretical and pedagogical underpinnings of the discipline shared by L1 and L2 practitioners; to point if possible towards any emerging consensus on good practice. The group determined that the principal aim of stylistics in the classroom is to make students aware of language use within chosen texts, and that what characterizes pedagogical stylistics is classroom activities that are interactive between the text and the (student) reader. Preliminary findings, from a pilot study involving a poem by Langston Hughes, suggest that the process of improving students’ linguistic sensibilities must include greater emphasis upon the text as action: i.e. upon the mental processing which is such a proactive part of reading and interpretation; and how all of these elements – pragmatic and cognitive as well as linguistic – function within quite specific social and cultural contexts.

An integrative framework for determining cross-national human resource management practices

Currently, debate in the area of cross-national human resource management (HRM) suggests that both “culture-bound” and “culture-free” factors and variables are important determinants of HRM policies and practices. HRM is presented as being context-specific and it is argued that with the growth of new markets world-wide, and increased levels of competition and globalization of business, there is a strong need for more cross-national HRM studies. However, the literature shows the absence of an integrated framework, which can help to highlight the different role that context-specific facets of HRM practices play. The nature of different determinants in different national and regional settings is rarely analyzed. This paper develops an integrated framework. It delineates the main distinctive facets associated with national factors, contingent variables, and organizational and human resource (HR) strategies and policies, that may be used to evaluate cross-national comparative HRM policies and practices.

Using grounded theory for theory building in operations management research:a study on inter-firm relationship governance

Purpose – Qualitative theory building approaches, such as grounded theory method (GTM), are still not very widespread and rigorously applied in operations management (OM) research. Yet it is agreed that more systematic observation of current industrial phenomena is necessary to help managers deal with their problems. The purpose of this paper is to provide an example to help guide other researchers on using GTM for theory building in OM research. Design/methodology/approach – A GTM study in the German automotive industry consisting of 31 interviews is followed by a validation stage comprising a survey (110 responses) and a focus group. Findings – The result is an example of conducting GTM research in OM, illustrated by the development of the novel collaborative enterprise governance framework for inter-firm relationship governance in the German automotive industry. Research limitations/implications – GTM is appropriate for qualitative theory building research, but the resultant theories need further testing. Research is necessary to identify the transferability of the collaborative enterprise governance concept to other industries than automotive, to other organisational areas than R&D and to product and service settings that are less complex and innovative. Practical implications – The paper helps researchers make more informed use of GTM when engaging in qualitative theory building research in OM. Originality/value – There is a lack of explicit and well-informed use of GTM in OM research because of poor understanding. This paper addresses this deficiency. The collaborative enterprise governance framework is a significant contribution in an area of growing importance within OM.

Empirical research into white racialized identities in Britain

The intellectual project of using whiteness as an explicit tool of analysis is not one that has taken root in Britain. However, there are a number of empirical studies that investigate the racialization of white identities. In this article, I look at some empirical sociological fieldwork carried out on white identities in Britain since the early 1990s and identify the key themes arising. These themes are (in)visibility, norms and values, cultural capital and integration, contingent hierarchies and Empire in the present. In Britain, a pertinent distinction is between rural and urban settings for the enactment of white identities vis-a`-vis those of minorities, and there is an exploration of some of the contingency that draws the boundary between ‘white’ and ‘Other’ in different places. Areas of commonality and distinctiveness are noted in terms of the American work. In the last section, I argue that there are a number of issues to resolve around continuing such studies, including linking the micro-level to the macro-level analysis, and expanding to international comparative work.

Improving the repeatability of heterochromatic flicker photometry for measurement of macular pigment optical density

Background: Heterochromatic flicker photometry (HFP) is a psychophysical technique used to measure macular pigment optical density (MPOD). We used the MPS 9000 (MPS) HFP device. Our aim was to determine if the repeatability of the MPS could be improved to make it more suitable for monitoring MPOD over time. Methods: Intra-session repeatability was assessed in 25 participants (aged 20-50 years). The resulting data was explored in detail, e.g., by examining the effect of removal and adjustment of data with less than optimal quality parameters. A protocol was developed for improved overall reliability, which was then tested in terms of inter-session repeatability in a separate group of 27 participants (aged 19-52 years). Results: Removal and adjustment of data reduced the intra-session coefficient of repeatability (CR) by 0.04, on average, and the mean individual standard deviation by 0.004. Raw data observation offered further insight into ways of improving repeatability. The proposed protocol resulted in an inter-session CR of 0.08. Conclusions: Removal and adjustment of less than optimal data improved repeatability, and is therefore recommended. To further improve repeatability, in brief we propose that each patient perform each part of the test twice, and a third time where necessary (described in detail by the protocol). Doing so will make the MPS more useful in research and clinical settings. © 2012 Springer-Verlag.

EU-ASEAN relations in the post-Cold War era:an analysis of the impact of normative factors on interregionalism

This thesis examines the relationship between the European Union (EU) and the Association of Southeast Asian Nations (ASEAN) with a focus on why their normative elements, e.g. values and norms, affect their ties in the post-Cold War era. Since the end of the Cold War, policy-makers and academics have become interested in region-to-region interaction, termed interregionalism. Though interregionalism is considered to have become an indelible feature of post-Cold War international politics, there are question marks over its importance. It is often argued that interregionalism reinforces the collective identity of the regional organisations involved. It is also maintained that its overall relevance to the international system depends on the level of actorness, which is primarily measured in institutional and material terms, of the participant regional organisations. This thesis contends that the normative components of the EU and ASEAN are also fundamental constituents of their actorness and, consequently, define significantly their interregionalism. This is based on a crucial observation that normative factors are of importance to the regional and international relations of the EU and ASEAN. Yet, while they strongly espouse norms and values to guide their internal and external activities, their normative premises radically differ from each other. Furthermore, these normative differences jeopardise their cooperation. Building on this observation the inquiry takes the normative components of the EU and ASEAN as the criterion as well as the focus for investigating their interregionalism. In doing so, it hypothesises that the EU and ASEAN are two different regional actors that adopt two dissimilar sets of norms to conduct their regional and international affairs and that such normative differences hinder their relations. Within this hypothesis, it seeks to address three central questions. First, what are the normative features that constitute the EU and ASEAN as actors in world politics and that make them different from each other? Second, what are the main sources of their normative differences? Finally, why do their normative differences become an obstructive factor in their relationship? To address these issues, the inquiry adopts a constructivist interpretation (of International Relations) and opts for a narrative and empirical inquiry, which is based on information and data acquired from official documents, scholarly works and interviews and questionnaires. In doing so, it finds that as they were born and evolved in two dissimilar temporal and spatial settings, the EU and ASEAN are two different norm entrepreneurs and normative powers. The former advocates a set of liberal cosmopolitan norms whereas the latter champions a set of traditional communitarian principles. Their normative differences become a major obstacle to their cooperation, especially when one regional organisation’s norms are refused or violated by the other. Thus, a key lesson drawn from these findings is that in order to explain more fully EU-ASEAN interregionalism, it is essential to consider their norms, the reasons behind their normative differences and the implication of those differences to their relations

System of integration of modularised assembly FMS

The modularised assembly FMS (Flexible Manufacturing System) cascade is a form of system design which, the authors feel, could be viable in a variety of organisational and operational settings where high product mix manufacture and unitary batch sizing are common features. The philosophy behind the concept is that production facilities are market-driven and customers' orders place a direct demand pull on final assembly which, in turn, triggers all preceeding activities. Greater flexibility~is recognized as a necessary feature in modern manufacture and the implementation of modularised FMS in conjunction with state-of-the-art hardware and computer software systems enable conditions under which more flexible processing can take place.