165 resultados para Investigative


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In Turpin v Allianz Australia Insurance Ltd (unreported, Supreme Court of Queensland, S5216 of 2001), Mullins J, 17.10.2001) the plaintiff applied for a declaration that the respondent disclose pursuant to s47 of the Motor Accident Insurance Act 1994 copies of three statements referred to in a loss assessor's investigation report as "attached". The issue involved determination of whether the statements must be disclosed under s48(2) even though protected by legal professional privilege. The Court applied the decision of the Queensland Court of Appeal in James v Workcover Queensland.

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Purpose We examined the age-dependent alterations and longitudinal course of subbasal nerve plexus (SNP) morphology in healthy individuals. Methods Laser-scanning corneal confocal microscopy, ocular screening, and health and metabolic assessment were performed on 64 healthy participants at baseline and at 12-month intervals for 3 years. At each annual visit, eight central corneal images of the SNP were selected and analyzed using a fully-automated analysis system to quantify corneal nerve fiber length (CNFL). Two linear mixed model approaches were fitted to examine the relationship between age and CNFL, and the longitudinal changes of CNFL over three years. Results At baseline, mean age was 51.9 ± 14.7 years. The cohort was sex balanced (χ2 = 0.56, P = 0.45). Age (t = 1.6, P = 0.12) and CNFL (t = -0.50, P = 0.62) did not differ between sexes. A total of 52 participants completed the 36-month visit and 49 participants completed all visits. Age had a significant effect on CNFL (F1,33 = 5.67, P = 0.02) with a linear decrease of 0.05 mm/mm2 in CNFL per one year increase in age. No significant change in CNFL was observed over the 36-month period (F1,55 = 0.69, P = 0.41). Conclusions The CNFL showed a stable course over a 36-month period in healthy individuals, although there was a slight linear reduction in CNFL with age. The findings of this study have implications for understanding the time-course of the effect of pathology and surgical or therapeutic interventions on the morphology of the SNP, and serves to confirm the suitability of CNFL as a screening/monitoring marker for peripheral neuropathies.

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Soluble endoglin is an anti-angiogenic protein that is released from the placenta and contributes to both maternal endothelial dysfunction and the clinical features of severe preeclampsia. The mechanism through which soluble endoglin is released from the placenta is currently unknown; however, recent work in colorectal cancer identified matrix metalloproteinase 14 (MMP-14) as the cleavage protease of endoglin. To determine whether this is also the mechanism responsible for soluble endoglin release in preeclampsia, we investigated the expression of MMP-14 within the placenta and the effects of its inhibition on soluble endoglin release. Placentas were obtained from severe, early onset preeclamptic pregnancies (n = 8) and gestationally matched preterm controls (n = 8). MMP-14 was predominately localized to the syncytiotrophoblast. Results from a proximity ligation assay showed protein interactions between endogenous MMP-14 and endoglin within the preeclamptic placenta. To demonstrate that this interaction produces soluble endoglin, we treated trophoblastic BeWo cells with either a broad-spectrum MMP inhibitor (GM6001) or MMP-14 siRNA. Both treatments produced a decrease in soluble endoglin (P ≤ 0.05). Treatment of mice bearing BeWo xenografts with GM6001 decreased circulating soluble endoglin levels in mouse serum (P ≤ 0.05). These findings indicate that MMP-14 is the likely cleavage protease of endoglin in the setting of preeclampsia. This approach provides a novel method for the development of potential therapeutics to reduce circulating soluble endoglin and ameliorate the clinical features of severe preeclampsia.

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A disintegrin and metalloprotease with thrombospondin motifs protein 1 (ADAMTS1) is a protease commonly up-regulated in metastatic carcinoma. Its overexpression in cancer cells promotes experimental metastasis, but whether ADAMTS1 is essential for metastatic progression is unknown. To address this question, we investigated mammary cancer progression and spontaneous metastasis in the MMTV-PyMT mouse mammary tumor model in Adamts1 knockout mice. Adamts1−/−/PyMT mice displayed significantly reduced mammary tumor and lung metastatic tumor burden and increased survival, compared with their wild-type and heterozygous littermates. Histological examination revealed an increased proportion of tumors with ductal carcinoma in situ and a lower proportion of high-grade invasive tumors in Adamts1−/−/PyMT mice, compared with Adamts1+/+/PyMT mice. Increased apoptosis with unaltered proliferation and vascular density in the Adamts1−/−/PyMT tumors suggested that reduced cell survival accounts for the lower tumor burden in ADAMTS1-deficient mice. Furthermore, Adamts1−/− tumor stroma had significantly lesser amounts of proteolytically cleaved versican and increased numbers of CD45+ leukocytes. Characterization of immune cell gene expression indicated that cytotoxic cell activation was increased in Adamts1−/− tumors, compared with Adamts1+/+ tumors. This finding is supported by significantly elevated IL-12+ cell numbers in Adamts1−/− tumors. Thus, in vivo ADAMTS1 may promote mammary tumor growth and progression to metastasis in the PyMT model and is a potential therapeutic target to prevent metastatic breast cancer.

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Olfactomedin-4 (OLFM-4) is an extracellular matrix protein that is highly expressed in human endometrium. We have examined the regulation and function of OLFM-4 in normal endometrium and in cases of endometriosis and endometrial cancer. OLFM-4 expression levels are highest in proliferative-phase endometrium, and 17 beta-estradiol up-regulates OLFM-4 mRNA in endometrial explant cultures. Using the luciferase reporter under control of the OLFM-4 promoter, it was shown that both 17 beta-estradiol and OH-tamoxifen induce luciferase activity, and epidermal growth factor receptor-1 is required for this estrogenic response. In turn, EGF activates the OLFM-4 promoter, and estrogen receptor-alpha is needed for the complete EGF response. The cellular functions of OLFM-4 were examined by its expression in OLFM-4-negative HEK-293 cells, which resulted in decreased vimentin expression and cell adherence as well as increased apoptosis resistance. In cases of endometriosis and endometrial cancer, OLFM-4 expression correlated with the presence of epidermal growth factor receptor-1 and estrogen receptor-alpha (or estrogen signaling). An increase of OLFM-4 mRNA was observed in the endometrium of endometriosis patients. No change in OLFM-4 expression levels were observed in patients with endometrial cancer relative with controts. In conclusion, cross-talk between estrogen and EGF signaling regulates OLFM-4 expression. The role of OLFM-4 in endometrial tissue remodeling before the secretory phase and during the predisposition and early events in endometriosis can be postulated but requires additional investigation. (Am J Pathol 2010, 177:2495-2508: DOI: 10.2353/ajpath.2010.100026

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Legacies of the Global Financial Crisis and major domestic corporate collapses – such as HIH Insurance Pty Ltd and One.Tel Ltd (telecommunications) – have significantly changed Australia‟s financial regulatory landscape. Legal requirements for auditors have attracted particular attention as have practice standards more broadly around disclosure and conflict of interest. Conversely, although successful detection and prosecution of breaches may rest in significant part on forensic accounting activities, Australia‟s practitioners in this field have no minimum training or qualifications standards other than the baseline requirements mandated by the country‟s three professional accounting bodies. For those unaffiliated with these organizations, no professional oversight exists. In Australia, growth in the forensic accounting industry has been in direct response to public demand for expertise in a broad range of fraud, forensic and business analytics areas in order to improve the corporate governance practices of Australian organizations. During the 1990s, Australian forensic accounting firms expanded and diversified into a number of different areas going well beyond just the examination of financial documents and involvement in financial litigation disputes. “Big 4” accounting firms such as PriceWaterhouseCoopers, KPMG, Deloitte and Ernst and Young formed independent forensic accounting or forensic services units; a number of mid-tier and „boutique‟ forensic accounting firms similarly expanded into forensic investigative, analytical and advisory services. By 2008, 800 forensic accountants were registered with the country‟s largest specialist forensic accounting group, the Forensic Accounting Special Interest Group (FASIG) of the ICAA1. Currently, obtaining more precise figures on numbers of forensic accounting practitioners is problematic: professional accounting bodies either do not keep a register or have ceased registering their forensic accounting members; lack of formal recognition, admission or certification processes complicate identification of candidates; and diversity of the skills sets the industry requires has meant the influx of non-accounting based specialists.

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Purpose: To determine the relative contributions of rods, cones and melanopsin to pupil responses in humans using temporal sinusoidal stimulation for light levels spanning the low mesopic to photopic range. Methods: A four-primary Ganzfeld photostimulator controlled flicker stimulations at seven light levels (-2.7 to 2 log cd/m2) and five frequencies (0.5 to 8Hz). Pupil diameter was measured using a high-resolution eyetracker. Three kinds of sinusoidal photoreceptor modulations were generated using silent substitution: 1) rod modulation, 2) cone modulation, and 3) combined rod and cone modulation in phase (Experiment 1) or phase shifted (Experiment 2) from a fixed rod phase. The melanopsin excitation was computed for each condition. A vector sum model was used to estimate the relative contribution of rods, cones and melanopsin to the pupil response. Results: From Experiment 1, the pupil frequency response peaked at 1Hz at two mesopic light levels for the three modulation conditions. Analyzing the rod-cone phase difference for the combined modulations (Experiment 2) identified a V-shaped response amplitude with a minimum between 135° and 180°. The pupil response phases increased as cone modulation phase increased. The pupil amplitude increased with increasing light level for cone and combined in-phase rod and cone modulation, but not for the rod modulation. Conclusions: These results demonstrate that cone- and rod-pathway contributions are more predominant than melanopsin contribution to the phasic pupil response. The combined rod, cone and melanopsin inputs to the phasic state of the pupil light reflex follow linear summation.

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Purpose: This study investigated the impact of simulated hyperopic anisometropia and sustained near work on performance of academic-related measures in children. Methods: Participants included 16 children (mean age: 11.1 ± 0.8 years) with minimal refractive error. Academic-related outcome measures included a reading test (Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (Developmental Eye Movement test). Performance was assessed with and without 0.75 D of imposed monocular hyperopic defocus (administered in a randomised order), before and after 20 minutes of sustained near work. Unilateral hyperopic defocus was systematically assigned to either the dominant or non-dominant sighting eye to evaluate the impact of ocular dominance on any performance decrements. Results: Simulated hyperopic anisometropia and sustained near work both independently reduced performance on all of the outcome measures (p<0.001). A significant interaction was also observed between simulated anisometropia and near work (p<0.05), with the greatest decrement in performance observed during simulated anisometropia in combination with sustained near work. Laterality of the refractive error simulation (ocular dominance) did not significantly influence the outcome measures (p>0.05). A reduction of up to 12% in performance was observed across the range of academic-related measures following sustained near work undertaken during the anisometropic simulation. Conclusion: Simulated hyperopic anisometropia significantly impaired academic–related performance, particularly in combination with sustained near work. The impact of uncorrected habitual anisometropia on academic-related performance in children requires further investigation.

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Purpose We designed a visual field test focused on the field utilized while driving to examine associations between field impairment and motor vehicle collision involvement in 2,000 drivers ≥70 years old. Methods The "driving visual field test" involved measuring light sensitivity for 20 targets in each eye, extending 15° superiorly, 30° inferiorly, 60° temporally and 30° nasally. The target locations were selected on the basis that they fell within the field region utilized when viewing through the windshield of a vehicle or viewing the dashboard while driving. Monocular fields were combined into a binocular field based on the more sensitive point from each eye. Severe impairment in the overall field or a region was defined as average sensitivity in the lowest quartile of sensitivity. At-fault collision involvement for five years prior to enrollment was obtained from state records. Poisson regression was used to calculate crude and adjusted rate ratios examining the association between field impairment and at-fault collision involvement. Results Drivers with severe binocular field impairment in the overall driving visual field had a 40% increased rate of at-fault collision involvement (RR 1.40, 95%CI 1.07-1.83). Impairment in the lower and left fields was associated with elevated collision rates (RR 1.40 95%CI 1.07-1.82 and RR 1.49, 95%CI 1.15-1.92, respectively), whereas impairment in the upper and right field regions was not. Conclusions Results suggest that older drivers with severe impairment in the lower or left region of the driving visual field are more likely to have a history of at-fault collision involvement.

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Purpose To investigate the effect of different levels of refractive blur on real-world driving performance measured under day and nighttime conditions. Methods Participants included 12 visually normal, young adults (mean age = 25.8 ± 5.2 years) who drove an instrumented research vehicle around a 4 km closed road circuit with three different levels of binocular spherical refractive blur (+0.50 diopter sphere [DS], +1.00 DS, +2.00 DS) compared with a baseline condition. The subjects wore optimal spherocylinder correction and the additional blur lenses were mounted in modified full-field goggles; the order of testing of the blur conditions was randomized. Driving performance was assessed in two different sessions under day and nighttime conditions and included measures of road signs recognized, hazard detection and avoidance, gap detection, lane-keeping, sign recognition distance, speed, and time to complete the course. Results Refractive blur and time of day had significant effects on driving performance (P < 0.05), where increasing blur and nighttime driving reduced performance on all driving tasks except gap judgment and lane keeping. There was also a significant interaction between blur and time of day (P < 0.05), such that the effects of blur were exacerbated under nighttime driving conditions; performance differences were evident even for +0.50 DS blur relative to baseline for some measures. Conclusions The effects of blur were greatest under nighttime conditions, even for levels of binocular refractive blur as low as +0.50 DS. These results emphasize the importance of accurate and up-to-date refractive correction of even low levels of refractive error when driving at night.

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Purpose People with diabetes have accelerated age-related biometric ocular changes compared with people without diabetes. We determined the effect of Type 1 diabetes on amplitude of accommodation. Method There were 43 participants (33 ± 8 years) with type 1 diabetes and 32 (34 ± 8 years) age-balanced participants without diabetes. There was no significant difference in the mean equivalent refractive error and visual acuity between the two groups. Amplitude of accommodation was measured using two techniques: objective — by determining the accommodative response to a stimulus in a COAS-HD wavefront aberrometer (Wavefront Sciences), and subjective — with a Badal hand optometer (Rodenstock). The influences of age and diabetes duration (in years) on amplitude of accommodation were analyzed using multiple regression analysis. Results Across both groups, objective amplitude was less than subjective amplitude by 1.4 ± 1.2 D. People with diabetes had lower objective (2.7 ± 1.6 D) and subjective (4.0 ± 1.7 D) amplitudes than people without diabetes (objective 4.1 ± 2.1 D, subjective 5.6 ± 2.1 D). For objective amplitude and the whole group, the duration of diabetes contributed 57% of the variation as did age. For the objective amplitude and only the diabetes group this was 78%. For subjective amplitude, the corresponding proportions were 68% and 103%. Conclusions Both objective and subjective techniques showed lowered amplitude of accommodation in participants with type 1 diabetes when compared with age-matched controls. The loss correlated strongly with duration of diabetes. The results suggest that individuals with diabetes will experience presbyopia earlier in life than people without diabetes, possibly due to metabolic changes in the lens.

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Purpose To investigate longitudinal changes of subbasal nerve plexus (SNP) morphology and its relationship with conventional measures of neuropathy in individuals with diabetes. Methods A cohort of 147 individuals with type 1 diabetes and 60 age-balanced controls underwent detailed assessment of clinical and metabolic factors, neurologic deficits, quantitative sensory testing, nerve conduction studies and corneal confocal microscopy at baseline and four subsequent annual visits. The SNP parameters included corneal nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL) and were quantified using a fully-automated algorithm. Linear mixed models were fitted to examine the changes in corneal nerve parameters over time. Results At baseline, 27% of the participants had mild diabetic neuropathy. All SNP parameters were significantly lower in the neuropathy group compared to controls (P<0.05). Overall, 89% of participants examined at baseline also completed the final visit. There was no clinically significant change to health and metabolic parameters and neuropathy measures from baseline to the final visit. Linear mixed model revealed a significant linear decline of CNFD (annual change rate, -0.9 nerve/mm2, P=0.01) in the neuropathy group compared to controls, which was associated with age (β=-0.06, P=0.04) and duration of diabetes (β=-0.08, P=0.03). In the neuropathy group, absolute changes of CNBD and CNFL showed moderate correlations with peroneal conduction velocity and cold sensation threshold, respectively (rs, 0.38 and 0.40, P<0.05). Conclusion This study demonstrates dynamic small fiber damage at the SNP, thus providing justification for our ongoing efforts to establish corneal nerve morphology as an appropriate adjunct to conventional measures of DPN.

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PURPOSE. To investigate effects of luminance and accommodation stimuli on pupil size and pupil center location and their implications for progressive addition lens wear. METHODS. Participants were young and older adult groups (n=20, 22±2 years, age range 18-25 years; n=19, 49±4 years, 45-58 years). A wave aberrometer included a relay system to allow a 12.5°x11° background for the internal fixation target. Participants viewed the target under a matrix of conditions with luminance levels 0.01, 3.7, 120 and 6100 cd/m² and with accommodation stimuli up to 6 diopters in 2 diopter steps. Pupil sizes and their centers, relative to limbus centers, were determined from anterior eye images. RESULTS. With luminance increase, reduction in pupil size was accentuated by increase in accommodation stimulus in the young, but not in the older, group. As luminance increased, pupil center location altered. This was nasally in both groups with an average shift of approximately 0.12mm. Relative to the lowest stimulus condition, the mean of the maximum absolute pupil center shifts was 0.26±0.08mm for both groups with individual shifts up to 0.5mm, findings consistent with previous studies. There was no significant effect of accommodation on pupil center locations for either age group, or evidence that location was influenced by the combination of luminance and accommodation stimulus that resulted in any particular pupil size. CONCLUSIONS. Variations in luminance and accommodation influence pupil size, but only the former affects pupil center location significantly. Pupil center shifts are too small to be of concern in fitting progressive addition lenses.

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Purpose: To investigate effects of pupil shifts, occurring with changes in luminance and accommodation stimuli, on refraction components and higher-order aberrations. Method: Participants were young and older groups (n=20, 22±2 years, age range 18–25 years; n=19, 49±4 years, 45–58 years). Aberrations/refractions at 4 mm and 3 mm diameters were compared between centered and decentered pupils for low (background 0.01cd/m², 0D), and high (6100cd/m², 4D or 6D) stimuli. Decentration was the difference between pupil centers for low and high stimuli. Clinical important changes with decentration were: M ±0.50D or ±0.25D, J180 and J45 ±0.25D or ±0.125D, HORMS ±0.05m, C(3, 1) ±0.05m, C(4, 0) ±0.05m. Results: Because of small pupil shifts in most participants (mean 0.26mm), there were few important changes in most refraction components and higher-order aberration terms. However, M changed by >0.25 D for a third of participants with 4mm pupils. When determining refractions from 2nd-6th order aberration coefficients, the more stringent criteria gave 76/ 534 (14%) possible important changes. Some participants had large pupil shifts with considerable aberration changes. Comparisons at the high stimulus were possible for only 11 participants because of small pupils. When refractions were determined from 2nd order aberration coefficients only, there were only 35 (7%) important changes for the more stringent criteria. Conclusion: Usually pupil shifts with changes in stimulus conditions have little influence on aberrations, but they can with high shifts. The number of aberrations orders that are considered as contributing to refraction influences the proportion of cases that might be considered clinically important.

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This research investigates relationships between parental socio economic status and daughters' career aspirations; linking family background and the career choices made by teenage girls. Drawing on Bourdieu's theory of cultural capital, and figures produced by the Bradley Report's investigation, two Queensland State High Schools are the investigative platform to address the research questions. A quantitative data analysis investigated if a correlation between the indicators existed. The significance of the findings will contribute to future decision making regarding educational practices and socio economic backgrounds and to support the Bradley Report target of 20% of low SES students accessing higher education. The outcomes found that female students' aspirations are influenced by parental background in a variety of significant ways. An understanding of these assists schools in understanding how to influence girls' future aspirations.