939 resultados para RAYLEIGH-LIKE DISSIPATION FUNCTION
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Introduction: The Trendelenburg Test (TT) is used to assess the functional strength of the hip abductor muscles (HABD), their ability to control frontal plane motion of the pelvis, and the ability of the lumbopelvic complex to transfer load into single leg stance. Rationale: Although a standard method to perform the test has been described for use within clinical populations, no study has directly investigated Trendelenburg’s hypotheses. Purpose: To investigate the validity of the TT using an ultrasound guided nerve block (UNB) of the superior gluteal nerve and determine whether the reduction in HABD strength would result in the theorized mechanical compensatory strategies measured during the TT. Methods: Quasi-experimental design using a convenience sample of nine healthy males. Only subjects with no current or previous injury to the lumbar spine, pelvis, or lower extremities, and no previous surgeries were included. Force dynamometry was used to evaluation HABD strength (%BW). 2D mechanics were used to evaluate contralateral pelvic drop (cMPD), change in contralateral pelvic drop (∆cMPD), ipsilateral hip adduction (iHADD) and ipsilateral trunk sway (TRUNK) measured in degrees (°). All measures were collected prior to and following a UNB on the superior gluteal nerve performed by an interventional radiologist. Results: Subjects’ age was median 31yrs (IQR:22-32yrs); and weight was median 73kg (IQR:67-81kg). An average 52% reduction of HABD strength (z=2.36,p=0.02) resulted following the UNB. No differences were found in cMPD or ∆cMPD (z=0.01,p= 0.99, z=-0.67,p=0.49). Individual changes in biomechanics show no consistency between subjects and non-systematic changes across the group. One subject demonstrated the mechanical compensations described by Trendelenburg. Discussion: The TT should not be used as screening measure for HABD strength in populations demonstrating strength greater than 30%BW but reserved for use with populations with marked HABD weakness. Importance: This study presents data regarding a critical level of HABD strength required to support the pelvis during the TT.
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Considerate amount of research has proposed optimization-based approaches employing various vibration parameters for structural damage diagnosis. The damage detection by these methods is in fact a result of updating the analytical structural model in line with the current physical model. The feasibility of these approaches has been proven. But most of the verification has been done on simple structures, such as beams or plates. In the application on a complex structure, like steel truss bridges, a traditional optimization process will cost massive computational resources and lengthy convergence. This study presents a multi-layer genetic algorithm (ML-GA) to overcome the problem. Unlike the tedious convergence process in a conventional damage optimization process, in each layer, the proposed algorithm divides the GA’s population into groups with a less number of damage candidates; then, the converged population in each group evolves as an initial population of the next layer, where the groups merge to larger groups. In a damage detection process featuring ML-GA, as parallel computation can be implemented, the optimization performance and computational efficiency can be enhanced. In order to assess the proposed algorithm, the modal strain energy correlation (MSEC) has been considered as the objective function. Several damage scenarios of a complex steel truss bridge’s finite element model have been employed to evaluate the effectiveness and performance of ML-GA, against a conventional GA. In both single- and multiple damage scenarios, the analytical and experimental study shows that the MSEC index has achieved excellent damage indication and efficiency using the proposed ML-GA, whereas the conventional GA only converges at a local solution.
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Purpose – This paper adds to growing research of psychiatric intensive care units (PICU) by recounting descriptions of psychiatric intensive care settings and discusses the perceptions held by nurses of the organisational interfaces, arrangements and provisions of care in these settings. Design/methodology/approach – Data gathered from focus groups held with nurses from two PICUs was used to establish terminology, defining attributes, related concepts, antecedents, values, processes and concepts related to current practices. A literature search was conducted to permit a review of the conceptual arrangements and contemporary understanding of intensive care for people experiencing acute psychiatric illness based on the perspectives held by the nurses from the focus groups. Findings – Dissonance between service needs and the needs and management of individual patients overshadow strategies to implement comprehensive recovery-oriented approaches. Three factors are reported in this paper that influence standards and procedural practice in PICU; organisational structures; physical structures; and subtype nomenclature. Practical implications – Acute inpatient care is an important part of a comprehensive approach to mental health services. Commonly intensive acute care is delivered in specialised wards or units co-located with acute mental health inpatient units mostly known as PICU. Evidence of the most effective treatment and approaches in intensive care settings that support comprehensive recovery for improved outcomes is nascent. Originality/value – Current descriptions from nurses substantiate wide variations in the provisions, design and classifications of psychiatric intensive care. Idiosyncratic and localised conceptions of psychiatric intensive care are not adequately entailing effective treatment and methods in support of recovery principles for improved and comprehensive outcomes. The authors suggest that more concrete descriptions, guidelines, training and policies for provision of intensive psychiatric health care encompassing the perspective of nursing professionals, would reinforce conceptual construction and thus optimum treatments within a comprehensive, recovery-oriented approach to mental health services.
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Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.
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Denial-of-service (DoS) attacks are a growing concern to networked services like the Internet. In recent years, major Internet e-commerce and government sites have been disabled due to various DoS attacks. A common form of DoS attack is a resource depletion attack, in which an attacker tries to overload the server's resources, such as memory or computational power, rendering the server unable to service honest clients. A promising way to deal with this problem is for a defending server to identify and segregate malicious traffic as earlier as possible. Client puzzles, also known as proofs of work, have been shown to be a promising tool to thwart DoS attacks in network protocols, particularly in authentication protocols. In this thesis, we design efficient client puzzles and propose a stronger security model to analyse client puzzles. We revisit a few key establishment protocols to analyse their DoS resilient properties and strengthen them using existing and novel techniques. Our contributions in the thesis are manifold. We propose an efficient client puzzle that enjoys its security in the standard model under new computational assumptions. Assuming the presence of powerful DoS attackers, we find a weakness in the most recent security model proposed to analyse client puzzles and this study leads us to introduce a better security model for analysing client puzzles. We demonstrate the utility of our new security definitions by including two hash based stronger client puzzles. We also show that using stronger client puzzles any protocol can be converted into a provably secure DoS resilient key exchange protocol. In other contributions, we analyse DoS resilient properties of network protocols such as Just Fast Keying (JFK) and Transport Layer Security (TLS). In the JFK protocol, we identify a new DoS attack by applying Meadows' cost based framework to analyse DoS resilient properties. We also prove that the original security claim of JFK does not hold. Then we combine an existing technique to reduce the server cost and prove that the new variant of JFK achieves perfect forward secrecy (the property not achieved by original JFK protocol) and secure under the original security assumptions of JFK. Finally, we introduce a novel cost shifting technique which reduces the computation cost of the server significantly and employ the technique in the most important network protocol, TLS, to analyse the security of the resultant protocol. We also observe that the cost shifting technique can be incorporated in any Diffine{Hellman based key exchange protocol to reduce the Diffie{Hellman exponential cost of a party by one multiplication and one addition.
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Universities are more and more challenged by the emerging global higher education market, facilitated by advances in Information and Communication Technologies (ICT). This requires them to reconsider their mission and direction in order to function effectively and efficiently, and to be responsive to changes in their environment. In the face of increasing demands and competitive pressures, Universities like other companies, seek to continuously innovate and improve their performance. Universities are considering co-operating or sharing, both internally and externally, in a wide range of areas to achieve cost effectiveness and improvements in performance. Shared services are an effective model for re-organizing to reduce costs, increase quality and create new capabilities. Shared services are not limited to the Higher Education (HE) sector. Organizations across different sectors are adopting shared services, in particular for support functions such as Finance, Accounting, Human Resources and Information Technology. While shared services has been around for more than three decades, commencing in the 1970’s in the banking sector and then been adopted by other sectors, it is an under researched domain, with little consensus on the most fundamental issues even as basic as defining what shared services is. Moreover, the interest in shared services within Higher Education is a global phenomenon. This study on shared services is situated within the Higher Education Sector of Malaysia, and originated as an outcome resulting from a national project (2005 – 2007) conducted by the Ministry of Higher Education (MOHE) entitled "Knowledge, Information Communication Technology Strategic Plan (KICTSP) for Malaysian Public Higher Education"- where progress towards more collaborations via shared services was a key recommendation. The study’s primary objective was to understand the nature and potential for ICT shared services, in particular in the Malaysian HE sector; by laying a foundation in terms of definition, typologies and research agenda and deriving theoretically based conceptualisations of the potential benefits of shared services, success factors and issues of pursuing shared services. The study embarked on this objective with a literature review and pilot case study as a means to further define the context of the study, given the current under-researched status of ICT shared services and of shared services in Higher Education. This context definition phase illustrated a range of unaddressed issues; including a lack of common understanding of what shared services are, how they are formed, what objectives they full fill, who is involved etc. The study thus embarked on a further investigation of a more foundational nature with an exploratory phase that aimed to address these gaps, where a detailed archival analysis of shared services literature within the IS context was conducted to better understand shared services from an IS perspective. The IS literature on shared services was analysed in depth to report on the current status of shared services research in the IS domain; in particular definitions, objectives, stakeholders, the notion of sharing, theories used, and research methods applied were analysed, which provided a firmer base to this study’s design. The study also conducted a detailed content analysis of 36 cases (globally) of shared services implementations in the HE sector to better understand how shared services are structured within the HE sector and what is been shared. The results of the context definition phase and exploratory phase formed a firm basis in the multiple case studies phase which was designed to address the primary goals of this study (as presented above). Three case sites within the Malaysian HE sector was included in this analysis, resulting in empirically supported theoretical conceptualizations of shared services success factors, issues and benefits. A range of contributions are made through this study. First, the detailed archival analysis of shared services in Information Systems (IS) demonstrated the dearth of research on shared services within Information Systems. While the existing literature was synthesised to contribute towards an improved understanding of shared services in the IS domain, the areas that are yet under-developed and requires further exploration is identified and presented as a proposed research agenda for the field. This study also provides theoretical considerations and methodological guidelines to support the research agenda; to conduct better empirical research in this domain. A number of literatures based a priori frameworks (i.e. on the forms of sharing and shared services stakeholders etc) are derived in this phase, contributing to practice and research with early conceptualisations of critical aspects of shared services. Furthermore, the comprehensive archival analysis design presented and executed here is an exemplary approach of a systematic, pre-defined and tool-supported method to extract, analyse and report literature, and is documented as guidelines that can be applied for other similar literature analysis, with particular attention to supporting novice researchers. Second, the content analysis of 36 shared services initiatives in the Higher Education sector presented eight different types of structural arrangements for shared services, as observed in practice, and the salient dimensions along which those types can be usefully differentiated. Each of the eight structural arrangement types are defined and demonstrated through case examples, with further descriptive details and insights to what is shared and how the sharing occurs. This typology, grounded on secondary empirical evidence, can serve as a useful analytical tool for researchers investigating the shared services phenomenon further, and for practitioners considering the introduction or further development of shared services. Finally, the multiple case studies conducted in the Malaysian Higher Education sector, provided further empirical basis to instantiate the conceptual frameworks and typology derived from the prior phases and develops an empirically supported: (i) framework of issues and challenges, (ii) a preliminary theory of shared services success, and (iii) a benefits framework, for shared services in the Higher Education sector.
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First principle calculations for a hexagonal (graphene-like) boron nitride (g-BN) monolayer sheet in the presence of a boron-atom vacancy show promising properties for capture and activation of carbon dioxide. CO2 is found to decompose to produce an oxygen molecule via an intermediate chemisorption state on the defect g-BN sheet. The three stationary states and two transition states in the reaction pathway are confirmed by minimum energy pathway search and frequency analysis. The values computed for the two energy barriers involved in this catalytic reaction after enthalpy correction indicate that the catalytic reaction should proceed readily at room temperature.
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In this letter the core-core-valence Auger transitions of an atomic impurity, both in bulk or adsorbed on a jellium-like surface, are computed within a DFT framework. The Auger rates calculated by the Fermi golden rule are compared with those determined by an approximate and simpler expression. This is based on the local density of states (LDOS) with a core hole present, in a region around the impurity nucleus. Different atoms, Na and Mg, solids, Al and Ag, and several impurity locations are considered. We obtain an excellent agreement between KL1V and KL23V rates worked out with the two approaches. The radius of the sphere in which we calculate the LDOS is the relevant parameter of the simpler approach. Its value only depends on the atomic species regardless of the location of the impurity and the type of substrate. (C) 2003 Elsevier B.V. All rights reserved.
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The sheep (Ovis aries) is commonly used as a large animal model in skeletal research. Although the sheep genome has been sequenced there are still only a limited number of annotated mRNA sequences in public databases. A complementary DNA (cDNA) library was constructed to provide a generic resource for further exploration of genes that are actively expressed in bone cells in sheep. It was anticipated that the cDNA library would provide molecular tools for further research into the process of fracture repair and bone homeostasis, and add to the existing body of knowledge. One of the hallmarks of cDNA libraries has been the identification of novel genes and in this library the full open reading frame of the gene C12orf29 was cloned and characterised. This gene codes for a protein of unknown function with a molecular weight of 37 kDa. A literature search showed that no previous studies had been conducted into the biological role of C12orf29, except for some bioinformatics studies that suggested a possible link with cancer. Phylogenetic analyses revealed that C12orf29 had an ancient pedigree with a homologous gene found in some bacterial taxa. This implied that the gene was present in the last common eukaryotic ancestor, thought to have existed more than 2 billion years ago. This notion was further supported by the fact that the gene is found in taxa belonging to the two major eukaryotic branches, bikonts and unikonts. In the bikont supergroup a C12orf29-like gene was found in the single celled protist Naegleria gruberi, whereas in the unikont supergroup, encompassing the metazoa, the gene is universal to all chordate and, therefore, vertebrate species. It appears to have been lost to the majority of cnidaria and protostomes taxa; however, C12orf29-like genes have been found in the cnidarian freshwater hydra and the protostome Pacific oyster. The experimental data indicate that C12orf29 has a structural role in skeletal development and tissue homeostasis, whereas in silico analysis of the human C12orf29 promoter region suggests that its expression is potentially under the control of the NOTCH, WNT and TGF- developmental pathways, as well SOX9 and BAPX1; pathways that are all heavily involved in skeletogenesis. Taken together, this investigation provides strong evidence that C12orf29 has a very important role in the chordate body plan, in early skeletal development, cartilage homeostasis, and also a possible link with spina bifida in humans.
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Physical activity has been identified as a key behaviour in determining an individual’s health and functioning. Adolescent physical inactivity has been shown to track strongly through to adulthood. Interventions in youth to promote and increase physical activity have had mixed results. The significant rise over the past decade in time spent by adolescents performing social networking may provide a unique opportunity for health promoters to interact with adolescents through a familiar medium. The purpose of was study is to investigate the potential utility of social networking and associated technologies for the promotion of physical activity amongst adolescents. Participants were recruited from two nondenominational same-sex private schools, from high socioeconomic backgrounds in Brisbane, Australia. A total of 112 (90.3%) participants had complete data sets and were included in the analysis. Account ownership and rates of access to some social networking sites were high. However, a combination of a lack of interest and additional risks associated with social networking utilities, means that caution should be undertaken prior to the commencement of any intervention seeking to increase engagement in physical activities through these mediums. Student smart phone access and interest in smart phone applications for physical activity promotion purposes were moderate, and may provide opportunities for samples of adolescents from high socioeconomic backgrounds who are more likely to have access to appropriate technologies. As technology advances, the rate of smart phone ownership as opposed to overall phone ownership is likely to steadily increase over time. Access and use of information technology by children likely to continue to become more convenient. This makes smart phone applications as a means for physical activity promotion progressively more practical, and a promising future option.
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A synthetic reevesite-like material has been shown to decolorize selected dyes and degrade phenolic contaminants photocatalytically in water when irradiated with visible light. This material can photoactively decolorize dyes such as bromophenol blue, bromocresol green, bromothymol blue, thymol blue and methyl orange in less than 15 min under visible light radiation in the absence of additional oxidizing agents. Conversely, phenolic compounds suc has phenol, p-chlorophenol and p-nitrophenol are photocat- alytically degraded in approximately 3hwith additional H2O2 when irradiated with visible light. These reactions offer potentially energy effective pathways for the removal of recalcitrant organic waste contaminants.
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Background: Side effects of the medications used for procedural sedation and analgesia in the cardiac catheterisation laboratory are known to cause impaired respiratory function. Impaired respiratory function poses considerable risk to patient safety as it can lead to inadequate oxygenation. Having knowledge about the conditions that predict impaired respiratory function prior to the procedure would enable nurses to identify at-risk patients and selectively implement intensive respiratory monitoring. This would reduce the possibility of inadequate oxygenation occurring. Aim: To identify pre-procedure risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory. Design: Retrospective matched case–control. Methods: 21 cases of impaired respiratory function were identified and matched to 113 controls from a consecutive cohort of patients over 18 years of age. Conditional logistic regression was used to identify risk factors for impaired respiratory function. Results: With each additional indicator of acute illness, case patients were nearly two times more likely than their controls to experience impaired respiratory function (OR 1.78; 95% CI 1.19–2.67; p = 0.005). Indicators of acute illness included emergency admission, being transferred from a critical care unit for the procedure or requiring respiratory or haemodynamic support in the lead up to the procedure. Conclusion: Several factors that predict the likelihood of impaired respiratory function were identified. The results from this study could be used to inform prospective studies investigating the effectiveness of interventions for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory.
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Impaired respiratory function (IRF) during procedural sedation and analgesia (PSA) poses considerable risk to patient safety as it can lead to inadequate oxygenation and ventilation. Risk factors that can be screened prior to the procedure have not been identified for the cardiac catheterization laboratory (CCL).
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Despite its potential multiple contributions to sustainable policy objectives, urban transit is generally not widely used by the public in terms of its market share compared to that of automobiles, particularly in affluent societies with low-density urban forms like Australia. Transit service providers need to attract more people to transit by improving transit quality of service. The key to cost-effective transit service improvements lies in accurate evaluation of policy proposals by taking into account their impacts on transit users. If transit providers knew what is more or less important to their customers, they could focus their efforts on optimising customer-oriented service. Policy interventions could also be specified to influence transit users’ travel decisions, with targets of customer satisfaction and broader community welfare. This significance motivates the research into the relationship between urban transit quality of service and its user perception as well as behaviour. This research focused on two dimensions of transit user’s travel behaviour: route choice and access arrival time choice. The study area chosen was a busy urban transit corridor linking Brisbane central business district (CBD) and the St. Lucia campus of The University of Queensland (UQ). This multi-system corridor provided a ‘natural experiment’ for transit users between the CBD and UQ, as they can choose between busway 109 (with grade-separate exclusive right-of-way), ordinary on-street bus 412, and linear fast ferry CityCat on the Brisbane River. The population of interest was set as the attendees to UQ, who travelled from the CBD or from a suburb via the CBD. Two waves of internet-based self-completion questionnaire surveys were conducted to collect data on sampled passengers’ perception of transit service quality and behaviour of using public transit in the study area. The first wave survey is to collect behaviour and attitude data on respondents’ daily transit usage and their direct rating of importance on factors of route-level transit quality of service. A series of statistical analyses is conducted to examine the relationships between transit users’ travel and personal characteristics and their transit usage characteristics. A factor-cluster segmentation procedure is applied to respodents’ importance ratings on service quality variables regarding transit route preference to explore users’ various perspectives to transit quality of service. Based on the perceptions of service quality collected from the second wave survey, a series of quality criteria of the transit routes under study was quantitatively measured, particularly, the travel time reliability in terms of schedule adherence. It was proved that mixed traffic conditions and peak-period effects can affect transit service reliability. Multinomial logit models of transit user’s route choice were estimated using route-level service quality perceptions collected in the second wave survey. Relative importance of service quality factors were derived from choice model’s significant parameter estimates, such as access and egress times, seat availability, and busway system. Interpretations of the parameter estimates were conducted, particularly the equivalent in-vehicle time of access and egress times, and busway in-vehicle time. Market segmentation by trip origin was applied to investigate the difference in magnitude between the parameter estimates of access and egress times. The significant costs of transfer in transit trips were highlighted. These importance ratios were applied back to quality perceptions collected as RP data to compare the satisfaction levels between the service attributes and to generate an action relevance matrix to prioritise attributes for quality improvement. An empirical study on the relationship between average passenger waiting time and transit service characteristics was performed using the service quality perceived. Passenger arrivals for services with long headways (over 15 minutes) were found to be obviously coordinated with scheduled departure times of transit vehicles in order to reduce waiting time. This drove further investigations and modelling innovations in passenger’ access arrival time choice and its relationships with transit service characteristics and average passenger waiting time. Specifically, original contributions were made in formulation of expected waiting time, analysis of the risk-aversion attitude to missing desired service run in the passengers’ access time arrivals’ choice, and extensions of the utility function specification for modelling passenger access arrival distribution, by using complicated expected utility forms and non-linear probability weighting to explicitly accommodate the risk of missing an intended service and passenger’s risk-aversion attitude. Discussions on this research’s contributions to knowledge, its limitations, and recommendations for future research are provided at the concluding section of this thesis.
Resumo:
Members of the insulin-like growth factor (IGF) family have been shown to play critical roles in normal growth and development, as well as in tumour biology. The IGF system is complex and the biological effects of the IGFs are determined by their diverse interactions between many molecules, including their interactions with extracellular matrix (ECM) proteins. Recent studies have demonstrated that IGFs associate with the ECM protein vitronectin (VN) through IGF-binding proteins (IGFBP) and that this interaction modulates IGF-stimulated biological functions, namely cell migration and cell survival through the cooperative involvement of the type-I IGF receptor (IGF-1R) and VN-binding integrins. Since IGFs play important roles in the transformation and progression of breast cancer and VN has been found to be over-expressed at the leading edge of breast tumours, this project aimed to describe the effects of IGF-I:VN interactions on breast cell function. This was undertaken to dissect the molecular mechanisms underlying IGF-I:VN-induced responses and to design inhibitors to block the effects of such interactions. The studies described herein demonstrate that the increase in migration of MCF-7 breast cancer cells in response to the IGF-I:IGFBP-5:VN complex is accompanied by differential expression of genes known to be involved in migration, invasion and/or survival, including Tissue-factor (TF), Stratifin (SFN), Ephrin-B2, Sharp-2 and PAI-1. This „migration gene signature‟ was confirmed using real-time PCR analysis. Substitution of the native IGF-I within the IGF-I:IGFBP:VN complex with the IGF-I analogue, \[L24]\[A31]-IGF-I, which has a reduced affinity for the IGF-1R, failed to stimulate cell migration and interestingly, also failed to induce the differential gene expression. This supports the involvement of the IGF-1R in mediating these changes in gene expression. Furthermore, lentiviral shRNA-mediated stable knockdown of TF and SFN completely abrogated the increased cell migration induced by IGF-I:IGFBP:VN complexes in MCF-7 cells. Indeed, when these cells were grown in 3D Matrigel™ cultures a decrease in the overall size of the 3D spheroids in response to the IGF-I:IGFBP:VN complexes was observed compared to the parental MCF-7 cells. This suggests that TF and SFN have a role in complex-stimulated cell survival. Moreover, signalling studies performed on cells with the reduced expression of either TF or SFN had a decreased IGF-1R activation, suggesting the involvement of signalling pathways downstream of IGF-1R in TF- and/or SFN-mediated cell migration and cell survival. Taken together, these studies provide evidence for a common mechanism activated downstream of the IGF-1R that induces the expression of the „migration gene signature‟ in response to the IGF-I:IGFBP:VN complex that confers breast cancer cells the propensity to migrate and survive. Given the functional significance of the interdependence of ECM and growth factor (GF) interactions in stimulating processes key to breast cancer progression, this project aimed at developing strategies to prevent such growth factor:ECM interactions in an effort to inhibit the downstream functional effects. This may result in the reduction in the levels of ECM-bound IGF-I present in close proximity to the cells, thereby leading to a reduction in the stimulation of IGF-1R present on the cell surface. Indeed, the inhibition of IGF-I-mediated effects through the disruption of its association with ECM would not alter the physiological levels of IGF-I and potentially only exert effects in situations where abnormal over expression of ECM proteins are found; namely carcinomas and hyperproliferative diseases. In summary, this PhD project has identified novel, innovative and realistic strategies that can be used in vitro to inhibit the functions exerted by the IGF-I:IGFBP:VN multiprotein complexes critical for cancer progression, with a potential to be translated into in vivo investigations. Furthermore, TF and SFN were found to mediate IGF-I:IGFBP:VN-induced effects, thereby revealing their potential to be used as therapeutic targets or as predictive biomarkers for the efficacy of IGF-1R targeting therapies in breast cancer patients. In addition to its therapeutic and clinical scope, this PhD project has significantly contributed to the understanding of the role of the IGF system in breast tumour biology by providing valuable new information on the mechanistic events underpinning IGF-I:VN-mediated effects on breast cell functions. Furthermore, this is the first instance where favourable binding sites for IGF-II, IGFBP-3 and IGFBP-5 on VN have been identified. Taken together, this study has functionally characterised the interactions between IGF-I and VN and through innovative strategies has provided a platform for the development of novel therapies targeting these interactions and their downstream effects.