265 resultados para Functional genomics


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Background: The proportion of older individuals in the driving population is predicted to increase in the next 50 years. This has important implications for driving safety as abilities which are important for safe driving, such as vision (which accounts for the majority of the sensory input required for driving), processing ability and cognition have been shown to decline with age. The current methods employed for screening older drivers upon re-licensure are also vision based. This study, which investigated social, behavioural and professional aspects involved with older drivers, aimed to determine: (i) if the current visual standards in place for testing upon re-licensure are effective in reducing the older driver fatality rate in Australia; (ii) if the recommended visual standards are actually implemented as part of the testing procedures by Australian optometrists; and (iii) if there are other non-standardised tests which may be better at predicting the on-road incident-risk (including near misses and minor incidents) in older drivers than those tests recommended in the standards. Methods: For the first phase of the study, state-based age- and gender-stratified numbers of older driver fatalities for 2000-2003 were obtained from the Australian Transportation Safety Bureau database. Poisson regression analyses of fatality rates were considered by renewal frequency and jurisdiction (as separate models), adjusting for possible confounding variables of age, gender and year. For the second phase, all practising optometrists in Australia were surveyed on the vision tests they conduct in consultations relating to driving and their knowledge of vision requirements for older drivers. Finally, for the third phase of the study to investigate determinants of on-road incident risk, a stratified random sample of 600 Brisbane residents aged 60 years and were selected and invited to participate using an introductory letter explaining the project requirements. In order to capture the number and type of road incidents which occurred for each participant over 12 months (including near misses and minor incidents), an important component of the prospective research study was the development and validation of a driving diary. The diary was a tool in which incidents that occurred could be logged at that time (or very close in time to which they occurred) and thus, in comparison with relying on participant memory over time, recall bias of incident occurrence was minimised. Association between all visual tests, cognition and scores obtained for non-standard functional tests with retrospective and prospective incident occurrence was investigated. Results: In the first phase,rivers aged 60-69 years had a 33% lower fatality risk (Rate Ratio [RR] = 0.75, 95% CI 0.32-1.77) in states with vision testing upon re-licensure compared with states with no vision testing upon re-licensure, however, because the CIs are wide, crossing 1.00, this result should be regarded with caution. However, overall fatality rates and fatality rates for those aged 70 years and older (RR=1.17, CI 0.64-2.13) did not differ between states with and without license renewal procedures, indicating no apparent benefit in vision testing legislation. For the second phase of the study, nearly all optometrists measured visual acuity (VA) as part of a vision assessment for re-licensing, however, 20% of optometrists did not perform any visual field (VF) testing and only 20% routinely performed automated VF on older drivers, despite the standards for licensing advocating automated VF as part of the vision standard. This demonstrates the need for more effective communication between the policy makers and those responsible for carrying out the standards. It may also indicate that the overall higher driver fatality rate in jurisdictions with vision testing requirements is resultant as the tests recommended by the standards are only partially being conducted by optometrists. Hence a standardised protocol for the screening of older drivers for re-licensure across the nation must be established. The opinions of Australian optometrists with regard to the responsibility of reporting older drivers who fail to meet the licensing standards highlighted the conflict between maintaining patient confidentiality or upholding public safety. Mandatory reporting requirements of those drivers who fail to reach the standards necessary for driving would minimise potential conflict between the patient and their practitioner, and help maintain patient trust and goodwill. The final phase of the PhD program investigated the efficacy of vision, functional and cognitive tests to discriminate between at-risk and safe older drivers. Nearly 80% of the participants experienced an incident of some form over the prospective 12 months, with the total incident rate being 4.65/10 000 km. Sixty-three percent reported having a near miss and 28% had a minor incident. The results from the prospective diary study indicate that the current vision screening tests (VA and VF) used for re-licensure do not accurately predict older drivers who are at increased odds of having an on-road incident. However, the variation in visual measurements of the cohort was narrow, also affecting the results seen with the visual functon questionnaires. Hence a larger cohort with greater variability should be considered for a future study. A slightly lower cognitive level (as measured with the Mini-Mental State Examination [MMSE]) did show an association with incident involvement as did slower reaction time (RT), however the Useful-Field-of-View (UFOV) provided the most compelling results of the study. Cut-off values of UFOV processing (>23.3ms), divided attention (>113ms), selective attention (>258ms) and overall score (moderate/ high/ very high risk) were effective in determining older drivers at increased odds of having any on-road incident and the occurrence of minor incidents. Discussion: The results have shown that for the 60-69 year age-group, there is a potential benefit in testing vision upon licence renewal. However, overall fatality rates and fatality rates for those aged 70 years and older indicated no benefit in vision testing legislation and suggests a need for inclusion of screening tests which better predict on-road incidents. Although VA is routinely performed by Australian optometrists on older drivers renewing their licence, VF is not. Therefore there is a need for a protocol to be developed and administered which would result in standardised methods conducted throughout the nation for the screening of older drivers upon re-licensure. Communication between the community, policy makers and those conducting the protocol should be maximised. By implementing a standardised screening protocol which incorporates a level of mandatory reporting by the practitioner, the ethical dilemma of breaching patient confidentiality would also be resolved. The tests which should be included in this screening protocol, however, cannot solely be ones which have been implemented in the past. In this investigation, RT, MMSE and UFOV were shown to be better determinants of on-road incidents in older drivers than VA and VF, however, as previously mentioned, there was a lack of variability in visual status within the cohort. Nevertheless, it is the recommendation from this investigation, that subject to appropriate sensitivity and specificity being demonstrated in the future using a cohort with wider variation in vision, functional performance and cognition, these tests of cognition and information processing should be added to the current protocol for the screening of older drivers which may be conducted at licensing centres across the nation.

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This study established that the core principle underlying categorisation of activities have the potential to provide more comprehensive outcomes than the recognition of activities because it takes into consideration activities other than directional locomotion.

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The last few years have seen dramatic advances in genomics, including the discovery of a large number of non-coding and antisense transcripts. This has revolutionised our understanding of multifaceted transcript structures found within gene loci and their roles in the regulation of development, neurogenesis and other complex processes. The recent and continuing surge of knowledge has prompted researchers to reassess and further dissect gene loci. The ghrelin gene (GHRL) gives rise to preproghrelin, which in turn produces ghrelin, a 28 amino acid peptide hormone that acts via the ghrelin receptor (growth hormone secretagogue receptor/GHSR 1a). Ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, and cancer development. A truncated receptor splice variant, GHSR 1b, does not bind ghrelin, but dimerises with GHSR 1a, and may act as a dominant negative receptor. The gene products of ghrelin and its receptor are frequently overexpressed in human cancer While it is well known that the ghrelin axis (ghrelin and its receptor) plays a range of important functional roles, little is known about the molecular structure and regulation of the ghrelin gene (GHRL) and ghrelin receptor gene (GHSR). This thesis reports the re-annotation of the ghrelin gene, discovery of alternative 5’ exons and transcription start sites, as well as the description of a number of novel splice variants, including isoforms with a putative signal peptide. We also describe the discovery and characterisation of a ghrelin antisense gene (GHRLOS), and the discovery and expression of a ghrelin receptor (growth hormone secretagogue receptor/GHSR) antisense gene (GHSR-OS). We have identified numerous ghrelin-derived transcripts, including variants with extended 5' untranslated regions and putative secreted obestatin and C-ghrelin transcripts. These transcripts initiate from novel first exons, exon -1, exon 0 and a 5' extended 1, with multiple transcription start sites. We used comparative genomics to identify, and RT-PCR to experimentally verify, that the proximal exon 0 and 5' extended exon 1 are transcribed in the mouse ghrelin gene, which suggests the mouse and human proximal first exon architecture is conserved. We have identified numerous novel antisense transcripts in the ghrelin locus. A candidate non-coding endogenous natural antisense gene (GHRLOS) was cloned and demonstrates very low expression levels in the stomach and high levels in the thymus, testis and brain - all major tissues of non-coding RNA expression. Next, we examined if transcription occurs in the antisense orientation to the ghrelin receptor gene, GHSR. A novel gene (GHSR-OS) on the opposite strand of intron 1 of the GHSR gene was identified and characterised using strand-specific RT-PCR and rapid amplification of cDNA ends (RACE). GHSR-OS is differentially expressed and a candidate non-coding RNA gene. In summary, this study has characterised the ghrelin and ghrelin receptor loci and demonstrated natural antisense transcripts to ghrelin and its receptor. Our preliminary work shows that the ghrelin axis generates a broad and complex transcriptional repertoire. This study provides the basis for detailed functional studies of the the ghrelin and GHSR loci and future studies will be needed to further unravel the function, diagnostic and therapeutic potential of the ghrelin axis.

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The purpose of this study was to characterise the functional outcome of 12 transfemoral amputees fitted with osseointegrated fixation using temporal gait characteristics. The objectives were (A) to present the cadence, duration of gait cycle, support and swing phases with an emphasis on the stride-to-stride and participant-to-participant variability, and (B) to compare these temporal variables with normative data extracted from the literature focusing on transfemoral amputees fitted with a socket and able-bodied participants. The temporal variables were extracted from the load applied on the residuum during straight level walking, which was collected at 200 Hz by a transducer. A total of 613 strides were assessed. The cadence (46±4 strides/min), the duration of the gait cycle (1.29±0.11 s), support (0.73±0.07 s, 57±3% of CG) and swing (0.56±0.07 s, 43±3% of GC) phases of the participants were 2% quicker, 3%, 6% shorter and 1% longer than transfemoral amputees using a socket as well as 11% slower, 9%, 6% and 13% longer than able-bodied, respectively. All combined, the results indicated that the fitting of an osseointegrated fixation has enabled this group of amputees to restore their locomotion with a highly functional level. Further longitudinal and cross-sectional studies would be required to confirm these outcomes. Nonetheless, the data presented can be used as benchmark for future comparisons. It can also be used as input in generic algorithms using templates of patterns of loading to recognise activities of daily living and to detect falls.

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Older drivers represent the fastest growing segment of the road user population. Cognitive and physiological capabilities diminishes with ages. The design of future in-vehicle interfaces have to take into account older drivers' needs and capabilities. Older drivers have different capabilities which impact on their driving patterns and subsequently on road crash patterns. New in-vehicle technology could improve safety, comfort and maintain elderly people's mobility for longer. Existing research has focused on the ergonomic and Human Machine Interface (HMI) aspects of in-vehicle technology to assist the elderly. However there is a lack of comprehensive research on identifying the most relevant technology and associated functionalities that could improve older drivers' road safety. To identify future research priorities for older drivers, this paper presents: (i) a review of age related functional impairments, (ii) a brief description of some key characteristics of older driver crashes and (iii) a conceptualisation of the most relevant technology interventions based on traffic psychology theory and crash data.

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Functional communication training was used to replace multiply determined problem behaviour in two boys with autism. Experiment 1 involved a functional analysis of several topographies of problem behaviour using a variation of the procedures described by Iwata, Dorsey, Slifer, Bauman, and Richman. Results suggested that aggression, self-injury, and disruption were multiply determined (i.e., maintained by both attention and access to preferred objects). Experiment 2 involved a multiple-baseline design across subjects. The focus of intervention was to replace aggression, self-injury, and disruption with functionally equivalent communicative alternatives. Both boys were taught alternative “mands” to recruit attention and request preferred objects. Acquisition of these alternative communication skills was associated with concurrent decreases in aggression, self-injury, and disruption. Results suggest that multiply determined challenging behaviour can be decreased by teaching an alternative communication skill to replace each assessed function of the problem behaviour.

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Intervention to reduce challenging behaviour may be enhanced when based on a prior functional analysis. The present study describes a discrete-trial approach for the functional analysis of aggressive behaviour in two boys with autism. Twenty brief assessment trials were conducted in the classroom by the teacher under each of three conditions (i.e., attention, task and tangible). The results showed a clear pattern to each child's aggressive behaviour and suggested logical intervention strategies, although the study is limited because it involved only two children. The discrete-trial approach would appear to represent a practical and ecologically valid technique for conducting a functional analysis of challenging behaviour in applied settings

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This paper examines the development of student functional thinking during a teaching experiment that was conducted in two classrooms with a total of 45 children whose average age was nine years and six months. The teaching comprised four lessons taught by a researcher, with a second researcher and classroom teacher acting as participant observers. These lessons were designed to enable students to build mental representations in order to explore the use of function tables by focusing on the relationship between input and output numbers with the intention of extracting the algebraic nature of the arithmetic involved. All lessons were videotaped. The results indicate that elementary students are not only capable of developing functional thinking but also of communicating their thinking both verbally and symbolically.

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Understanding the complexities that are involved in the genetics of multifactorial diseases is still a monumental task. In addition to environmental factors that can influence the risk of disease, there is also a number of other complicating factors. Genetic variants associated with age of disease onset may be different from those variants associated with overall risk of disease, and variants may be located in positions that are not consistent with the traditional protein coding genetic paradigm. Latent Variable Models are well suited for the analysis of genetic data. A latent variable is one that we do not directly observe, but which is believed to exist or is included for computational or analytic convenience in a model. This thesis presents a mixture of methodological developments utilising latent variables, and results from case studies in genetic epidemiology and comparative genomics. Epidemiological studies have identified a number of environmental risk factors for appendicitis, but the disease aetiology of this oft thought useless vestige remains largely a mystery. The effects of smoking on other gastrointestinal disorders are well documented, and in light of this, the thesis investigates the association between smoking and appendicitis through the use of latent variables. By utilising data from a large Australian twin study questionnaire as both cohort and case-control, evidence is found for the association between tobacco smoking and appendicitis. Twin and family studies have also found evidence for the role of heredity in the risk of appendicitis. Results from previous studies are extended here to estimate the heritability of age-at-onset and account for the eect of smoking. This thesis presents a novel approach for performing a genome-wide variance components linkage analysis on transformed residuals from a Cox regression. This method finds evidence for a dierent subset of genes responsible for variation in age at onset than those associated with overall risk of appendicitis. Motivated by increasing evidence of functional activity in regions of the genome once thought of as evolutionary graveyards, this thesis develops a generalisation to the Bayesian multiple changepoint model on aligned DNA sequences for more than two species. This sensitive technique is applied to evaluating the distributions of evolutionary rates, with the finding that they are much more complex than previously apparent. We show strong evidence for at least 9 well-resolved evolutionary rate classes in an alignment of four Drosophila species and at least 7 classes in an alignment of four mammals, including human. A pattern of enrichment and depletion of genic regions in the profiled segments suggests they are functionally significant, and most likely consist of various functional classes. Furthermore, a method of incorporating alignment characteristics representative of function such as GC content and type of mutation into the segmentation model is developed within this thesis. Evidence of fine-structured segmental variation is presented.

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In this study, cell sheets comprising multilayered porcine bone marrow stromal cells (BMSC) were assembled with fully interconnected scaffolds made from medical-grade polycaprolactone–calcium phosphate (mPCL–CaP), for the engineering of structural and functional bone grafts. The BMSC sheets were harvested from culture flasks and wrapped around pre-seeded composite scaffolds. The layered cell sheets integrated well with the scaffold/cell construct and remained viable, with mineralized nodules visible both inside and outside the scaffold for up to 8 weeks culture. Cells within the constructs underwent classical in vitro osteogenic differentiation with the associated elevation of alkaline phosphatase activity and bone-related protein expression. In vivo, two sets of cell-sheet-scaffold/cell constructs were transplanted under the skin of nude rats. The first set of constructs (554mm3) were assembled with BMSC sheets and cultured for 8 weeks before implantation. The second set of constructs (10104mm3) was implanted immediately after assembly with BMSC sheets, with no further in vitro culture. For both groups, neo cortical and well-vascularised cancellous bone were formed within the constructs with up to 40% bone volume. Histological and immunohistochemical examination revealed that neo bone tissue formed from the pool of seeded BMSC and the bone formation followed predominantly an endochondral pathway, with woven bone matrix subsequently maturing into fully mineralized compact bone; exhibiting the histological markers of native bone. These findings demonstrate that large bone tissues similar to native bone can be regenerated utilizing BMSC sheet techniques in conjunction with composite scaffolds whose structures are optimized from a mechanical, nutrient transport and vascularization perspective.

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Background: The Functional Capacity Index (FCI) was designed to predict physical function 12 months after injury. We report a validation study of the FCI. Methods: This was a consecutive case series registered in the Queensland Trauma Registry who consented to the prospective 12-month telephone-administered follow-up study. FCI scores measured at 12 months were compared with those originally predicted. Results: Complete Abbreviated Injury Scale score information was available for 617 individuals, of whom 587 (95%) could be assigned at least one FCI score (range, 1-17). Agreement between the largest predicted FCI and observed FCI score was poor ([kappa] = 0.05; 95% confidence interval, 0.00-0.10) and explained only 1% of the variability in observed FCI. Using an encompassing model that included all FCI assignments, agreement remained poor ([kappa] = 0.05; 95% confidence interval, -0.02-0.12), and the model explained only 9% of the variability in observed FCI. Conclusion: The predicted functional capacity poorly agrees with actual functional outcomes. Further research should consider including other (noninjury) explanatory factors in predicting FCI at 12 months.

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Purpose: The purpose of this paper is to explore the role of cross-functional teams in the alignment between system effectiveness and operational effectiveness after the implementation of enterprise information systems (EIS). In addition, it aims to explore the contribution of cross-functional teams to improvement in operational performance. ---------- Design/methodology/approach: The research uses a combination of qualitative and quantitative methods, in a two-stage methodological approach, to investigate the influence of cross-functional teams on the alignment between system effectiveness and operational effectiveness and the impact of the stated alignment on the improvement in operational performance. ---------- Findings: Initial findings suggest that factors stemming from system effectiveness and the performance objectives stemming from operational effectiveness are important and significantly well correlated factors that promote the alignment between the effectiveness of technological implementation and the effectiveness of operations. In addition, confirmatory factor analysis has been used to find the structural relationships and provide explanations for the stated alignment and the contribution of cross-functional teams to the improvement in operational performance. ---------- Research limitations/implications: The principal limitation of this study is its small sample size. ---------- Practical implications: Cross-functional teams have been used by many organisations as a way of involving expertise from different functional areas in the implementation of innovative technologies. An appropriate use of the dimensions that emerged from this research, in the context of cross-functional teams, will assist organisations to properly utilise cross-functional teams with the aim of improving operational performance. ---------- Originality/value: The paper presents a new approach to measure the effectiveness of EIS implementation by adding new dimensions to measure it.

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Objective: During hospitalisation older people often experience functional decline which impacts on their future independence. The objective of this study was to evaluate a multifaceted transitional care intervention including home-based exercise strategies for at-risk older people on functional status, independence in activities of daily living, and walking ability. Methods: A randomised controlled trial was undertaken in a metropolitan hospital in Australia with 128 patients (64 intervention, 64 control) aged over 65 years with an acute medical admission and at least one risk factor for hospital readmission. The intervention group received an individually tailored program for exercise and follow-up care which was commenced in hospital and included regular visits in hospital by a physiotherapist and a Registered Nurse, a home visit following discharge, and regular telephone follow-up for 24 weeks following discharge. The program was designed to improve health promoting behaviours, strength, stability, endurance and mobility. Data were collected at baseline, then 4, 12 and 24 weeks following discharge using the Index of Activities of Daily Living (ADL), Instrumental Index of Activities of Daily Living (IADL), and the Walking Impairment Questionnaire (Modified). Results: Significant improvements were found in the intervention group in IADL scores (p<.001), ADL scores (p<.001), and WIQ scale scores (p<.001) in comparison to the control group. The greatest improvements were found in the first four weeks following discharge. Conclusions: Early introduction of a transitional model of care incorporating a tailored exercise program and regular telephone follow-up for hospitalised at-risk older adults can improve independence and functional ability.