Persons with age-related maculopathy risk genotypes and clinically normal eyes have reduced mesopic vision

PURPOSE: To determine if participants with normal visual acuity, no ophthalmoscopically signs of age-related maculopathy (ARM) in both eyes and who are carriers of the CFH, LOC387715 and HRTA1 high-risk genotypes (“gene-positive”) have impaired rod- and cone-mediated mesopic visual function compared to persons who do not carry the risk genotypes (“gene-negative”).---------- METHODS: Fifty-three Caucasian study participants (mean 55.8 ± 6.1) were genotyped for CFH, LOC387715/ARMS2 and HRTA1 polymorphisms. We genotyped single nucleotide polymorphisms (SNPs) in the CFH (rs380390), LOC387715/ARMS2 (rs10490924) and HTRA1 (rs11200638) genes using Applied Biosystems optimised TaqMan assays. We determined the critical fusion frequency (CFF) mediated by cones alone (Long, Middle and Short wavelength sensitive cones; LMS) and by the combined activities of cones and rods (LMSR). The stimuli were generated using a 4-primary photostimulator that provides independent control of the photoreceptor excitation under mesopic light levels. Visual function was further assessed using standard clinical tests, flicker perimetry and microperimetry.---------- RESULTS: The mesopic CFF mediated by rods and cones (LMSR) was significantly reduced in gene-positive compared to gene-negative participants after correction for age (p=0.03). Cone-mediated CFF (LMS) was not significantly different between gene-positive and -negative participants. There were no significant associations between flicker perimetry and microperimetry and genotype.---------- CONCLUSIONS: This is the first study to relate ARM risk genotypes with mesopic visual function in clinically normal persons. These preliminary results could become of clinical importance as mesopic vision may be used to document sub-clinical retinal changes in persons with risk genotypes and to determine whether those persons progress into manifest disease.

Effect of surgical approach on bone vascularisation, fracture and soft tissue healing : comparison of less invasive to open approach

Over the past ten years, minimally invasive plate osteosynthesis (MIPO) for the fixation of long bone fractures has become a clinically accepted method with good outcomes, when compared to the conventional open surgical approach (open reduction internal fixation, ORIF). However, while MIPO offers some advantages over ORIF, it also has some significant drawbacks, such as a more demanding surgical technique and increased radiation exposure. No clinical or experimental study to date has shown a difference between the healing outcomes in fractures treated with the two surgical approaches. Therefore, a novel, standardised severe trauma model in sheep has been developed and validated in this project to examine the effect of the two surgical approaches on soft tissue and fracture healing. Twenty four sheep were subjected to severe soft tissue damage and a complex distal femur fracture. The fractures were initially stabilised with an external fixator. After five days of soft tissue recovery, internal fixation with a plate was applied, randomised to either MIPO or ORIF. Within the first fourteen days, the soft tissue damage was monitored locally with a compartment pressure sensor and systemically by blood tests. The fracture progress was assessed fortnightly by x-rays. The sheep were sacrificed in two groups after four and eight weeks, and CT scans and mechanical testing performed. Soft tissue monitoring showed significantly higher postoperative Creatine Kinase and Lactate Dehydrogenase values in the ORIF group compared to MIPO. After four weeks, the torsional stiffness was significantly higher in the MIPO group (p=0.018) compared to the ORIF group. The torsional strength also showed increased values for the MIPO technique (p=0.11). The measured total mineralised callus volumes were slightly higher in the ORIF group. However, a newly developed morphological callus bridging score showed significantly higher values for the MIPO technique (p=0.007), with a high correlation to the mechanical properties (R2=0.79). After eight weeks, the same trends continued, but without statistical significance. In summary, this clinically relevant study, using the newly developed severe trauma model in sheep, clearly demonstrates that the minimally invasive technique minimises additional soft tissue damage and improves fracture healing in the early stage compared to the open surgical approach method.

Magnocellular and parvocellular pathway mediated luminance contrast discrimination in amblyopia

To evaluate whether luminance contrast discrimination losses in amblyopia on putative magnocellular (MC) and parvocellular (PC) pathway tasks reflect deficits at retinogeniculate or cortical sites. Fifteen amblyopes including six anisometropes, seven strabismics, two mixed and 12 age-matched controls were investigated. Contrast discrimination was measured using established psychophysical procedures that differentiate MC and PC processing. Data were described with a model of the contrast response of primate retinal ganglion cells. All amblyopes and controls displayed the same contrast signatures on the MC and PC tasks, with three strabismics having reduced sensitivity. Amblyopic PC contrast gain was similar to electrophysiological estimates from visually normal, non-human primates. Sensitivity losses evident in a subset of the amblyopes reflect cortical summation deficits, with no change in retinogeniculate contrast responses. The data do not support the proposal that amblyopic contrast sensitivity losses on MC and PC tasks reflect retinogeniculate deficits, but rather are due to anomalous post-retinogeniculate cortical processing of retinal signals.

The effect of presbyiopic vision corrections on nighttime driving performance

Purpose. To investigate the effect of various presbyopic vision corrections on nighttime driving performance on a closed-road driving circuit. Methods. Participants were 11 presbyopes (mean age, 57.3 ± 5.8 years), with a mean best sphere distance refractive error of R+0.23±1.53 DS and L+0.20±1.50 DS, whose only experience of wearing presbyopic vision correction was reading spectacles. The study involved a repeated-measures design by which a participant's nighttime driving performance was assessed on a closed-road circuit while wearing each of four power-matched vision corrections. These included single-vision distance lenses (SV), progressive-addition spectacle lenses (PAL), monovision contact lenses (MV), and multifocal contact lenses (MTF CL) worn in a randomized order. Measures included low-contrast road hazard detection and avoidance, road sign and near target recognition, lane-keeping, driving time, and legibility distance for street signs. Eye movement data (fixation duration and number of fixations) were also recorded. Results. Street sign legibility distances were shorter when wearing MV and MTF CL than SV and PAL (P < 0.001), and participants drove more slowly with MTF CL than with PALs (P = 0.048). Wearing SV resulted in more errors (P < 0.001) and in more (P = 0.002) and longer (P < 0.001) fixations when responding to near targets. Fixation duration was also longer when viewing distant signs with MTF CL than with PAL (P = 0.031). Conclusions. Presbyopic vision corrections worn by naive, unadapted wearers affected nighttime driving. Overall, spectacle corrections (PAL and SV) performed well for distance driving tasks, but SV negatively affected viewing near dashboard targets. MTF CL resulted in the shortest legibility distance for street signs and longer fixation times.

Analysis of the effect of negation on information retrieval of medical data

Most information retrieval (IR) models treat the presence of a term within a document as an indication that the document is somehow "about" that term, they do not take into account when a term might be explicitly negated. Medical data, by its nature, contains a high frequency of negated terms - e.g. "review of systems showed no chest pain or shortness of breath". This papers presents a study of the effects of negation on information retrieval. We present a number of experiments to determine whether negation has a significant negative affect on IR performance and whether language models that take negation into account might improve performance. We use a collection of real medical records as our test corpus. Our findings are that negation has some affect on system performance, but this will likely be confined to domains such as medical data where negation is prevalent.

Effect of pedestrian movement on MIMO-OFDM channel capacity in an indoor environment

The rapid growth of mobile telephone use, satellite services, and now the wireless Internet and WLANs are generating tremendous changes in telecommunication and networking. As indoor wireless communications become more prevalent, modeling indoor radio wave propagation in populated environments is a topic of significant interest. Wireless MIMO communication exploits phenomena such as multipath propagation to increase data throughput and range, or reduce bit error rates, rather than attempting to eliminate effects of multipath propagation as traditional SISO communication systems seek to do. The MIMO approach can yield significant gains for both link and network capacities, with no additional transmitting power or bandwidth consumption when compared to conventional single-array diversity methods. When MIMO and OFDM systems are combined and deployed in a suitable rich scattering environment such as indoors, a significant capacity gain can be observed due to the assurance of multipath propagation. Channel variations can occur as a result of movement of personnel, industrial machinery, vehicles and other equipment moving within the indoor environment. The time-varying effects on the propagation channel in populated indoor environments depend on the different pedestrian traffic conditions and the particular type of environment considered. A systematic measurement campaign to study pedestrian movement effects in indoor MIMO-OFDM channels has not yet been fully undertaken. Measuring channel variations caused by the relative positioning of pedestrians is essential in the study of indoor MIMO-OFDM broadband wireless networks. Theoretically, due to high multipath scattering, an increase in MIMO-OFDM channel capacity is expected when pedestrians are present. However, measurements indicate that some reductions in channel capacity could be observed as the number of pedestrians approaches 10 due to a reduction in multipath conditions as more human bodies absorb the wireless signals. This dissertation presents a systematic characterization of the effects of pedestrians in indoor MIMO-OFDM channels. Measurement results, using the MIMO-OFDM channel sounder developed at the CSIRO ICT Centre, have been validated by a customized Geometric Optics-based ray tracing simulation. Based on measured and simulated MIMO-OFDM channel capacity and MIMO-OFDM capacity dynamic range, an improved deterministic model for MIMO-OFDM channels in indoor populated environments is presented. The model can be used for the design and analysis of future WLAN to be deployed in indoor environments. The results obtained show that, in both Fixed SNR and Fixed Tx for deterministic condition, the channel capacity dynamic range rose with the number of pedestrians as well as with the number of antenna combinations. In random scenarios with 10 pedestrians, an increment in channel capacity of up to 0.89 bits/sec/Hz in Fixed SNR and up to 1.52 bits/sec/Hz in Fixed Tx has been recorded compared to the one pedestrian scenario. In addition, from the results a maximum increase in average channel capacity of 49% has been measured while 4 antenna elements are used, compared with 2 antenna elements. The highest measured average capacity, 11.75 bits/sec/Hz, corresponds to the 4x4 array with 10 pedestrians moving randomly. Moreover, Additionally, the spread between the highest and lowest value of the the dynamic range is larger for Fixed Tx, predicted 5.5 bits/sec/Hz and measured 1.5 bits/sec/Hz, in comparison with Fixed SNR criteria, predicted 1.5 bits/sec/Hz and measured 0.7 bits/sec/Hz. This has been confirmed by both measurements and simulations ranging from 1 to 5, 7 and 10 pedestrians.

Corona ions from overhead transmission voltage powerlines : effect on DC e-field and ambient particle concentration levels

Along with their essential role in electricity transmission and distribution, some powerlines also generate large concentrations of corona ions. This study aimed at comprehensive investigation of corona ions, vertical dc e-field, ambient aerosol particle charge and particle number concentration levels in the proximity of some high/sub-transmission voltage powerlines. The influence of meteorology on the instantaneous value of these parameters, and the possible existence of links or associations between the parameters measured were also statistically investigated. The presence of positive and negative polarities of corona ions was associated with variation in the mean vertical dc e-field, ambient ion and particle charge concentration level. Though these variations increased with wind speed, their values also decreased with distance from the powerlines. Predominately positive polarities of ions were recorded up to a distance of 150 m (with the maximum values recorded 50 m downwind of the powerlines). At 200 m from the source, negative ions predominated. Particle number concentration levels however remained relatively constant (103 particle cm-3) irrespective of the sampling site and distance from the powerlines. Meteorological factors of temperature, humidity and wind direction showed no influence on the electrical parameters measured. The study also discovered that e-field measurements were not necessarily a true representation of the ground-level ambient ion/particle charge concentrations.

Effect of cabin ventilation rate on ultrafine particle exposure inside automobiles

We alternately measured on-road and in-vehicle ultrafine (<100 nm) particle (UFP) concentration for 5 passenger vehicles that comprised an age range of 18 years. A range of cabin ventilation settings were assessed during 301 trips through a 4 km road tunnel in Sydney, Australia. Outdoor airflow(ventilation) rates under these settings were quantified on open roads using tracer gas techniques. Significant variability in tunnel trip average median in-cabin/on-road (I/O) UFP ratios was observed (0.08 to ∼1.0). Based on data spanning all test automobiles and ventilation settings, a positive linear relationship was found between outdoor air flow rate and I/O ratio, with the former accounting for a substantial proportion of variation in the latter (R2 ) 0.81). UFP concentrations recorded in cabin during tunnel travel were significantly higher than those reported by comparable studies performed on open roadways. A simple mathematical model afforded the ability to predict tunnel trip average in-cabin UFP concentrations with good accuracy. Our data indicate that under certain conditions, in-cabin UFP exposures incurred during tunnel travel may contribute significantly to daily exposure. The UFP exposure of automobile occupants appears strongly related to their choice of ventilation setting and vehicle.

Effect of clear zone widths on run-off-road crash outcomes

Current guidelines on clear zone selection and roadside hazard management adopt the US approach based on the likelihood of roadside encroachment by drivers. This approach is based on the available research conducted in the 1960s and 70s. Over time, questions have been raised regarding the robustness and applicability of this research in Australasia in 2010 and in the Safe System context. This paper presents a review of the fundamental research relating to selection of clear zones. Results of extensive rural highway statistical data modelling suggest that a significant proportion of run-off-road to the left casualty crashes occurs in clear zones exceeding 13 m. They also show that the risk of run-off-road to the left casualty crashes was 21% lower where clear zones exceeded 8 m when compared with clear zones in the 4 – 8 m range. The paper discusses a possible approach to selection of clear zones based on managing crash outcomes, rather than on the likelihood of roadside encroachment which is the basis for the current practice. It is expected that this approach would encourage selection of clear zones wider than 8 m when the combination of other road features suggests higher than average casualty crash risk.

Cross-talk of subchondral bone osteoblasts and articular cartilage chondrocytes : a new insight in understanding osteoarthritis pathogenesis

Osteoarthritis (OA) is the most common musculoskeletal disorder and represents a major health burden to society. In the course of the pathological development of OA, articular cartilage chondrocytes (ACCs) undergo atypical phenotype changes characterized by the expression of hypertrophic differentiation markers. Also, the adjacent subchondral bone shows signs of abnormal mineral density and enhanced production of bone turnover markers, indicative of osteoblast dysfunction. Collectively these findings indicate that the pathological changes typical of OA, involve alterations of the phenotypic properties of cells in both the subchondral bone and articular cartilage. However, the mechanism(s) by which these changes occur during OA development are not completely understood. The purpose of this project was to address the question of how subchondral bone osteoblasts (SBOs) and ACCs interact with each other with respect to regulation of respective cells’ phenotypic properties and in particular the involvement of mitogen activated protein kinase (MAPK) signalling pathways under normal and OA joint condition. We also endeavoured to test the influence of cross-talk between SBOs and ACCs isolated from normal and OA joint on matrix metalloproteinase (MMP) expression. For this purpose tissues from the knees of OA patients and normal controls were collected to isolate SBOs and ACCs. The cellular cross-talk of SBOs and ACCs were studied by means of both direct and indirect co-culture systems, which made it possible to identify the role of both membrane bound and soluble factors. Histology, immunohistochemistry, qRT-PCR, zymography, ELISA and western blotting were some of the techniques applied to distinguish the changes in the co-cultured vs. non co-cultured cells. The MAPK signalling pathways were probed by using targeted MAPK inhibitors, and their activity monitored by western blot analysis using phospho MAPK specific antibodies. Our co-culture studies demonstrated that OA ACCs enhanced the SBOs differentiation compared to normal ACCs. We demonstrated that OA ACCs induced these phenotypic changes in the SBOs via activating an ERK1/2 signalling pathway. The findings from this study thus provided clear evidence that OA ACCs play an integral role in altering the SBO phenotype. In the second study, we tested the influence of normal SBOs and OA SBOs on ACCs phenotype changes. The results showed that OA SBOs increased the hypertrophic gene expression in co-cultured ACCs compared to normal SBOs, a phenotype which is considered as pathological to the health and integrity of articular cartilage. It was demonstrated that these phenotype changes occurred via de-activation of p38 and activation of ERK1/2 signaling pathways. These findings suggest that the pathological interaction of OA SBOs with ACCs is mediated by cross-talking between ERK1/2 and p38 pathways, resulting in ACCs undergoing hypertrophic differentiation. Subsequent experiments to determine the effect on MMP regulation, of SBOs and ACCs cross-talk, revealed that co-culturing OA SBOs with ACCs significantly enhanced the proteolytic activity and expression of MMP-2 and MMP-9. In turn, co-culture of OA ACCs with SBOs led to abundant MMP-2 expression in SBOs. Furthermore, we showed that the addition of ERK1/2 and JNK inhibitors reversed the elevated MMP-2 and MMP-9 production which otherwise resulted from the interactions of OA SBOs-ACCs. Thus, this study has demonstrated that the altered interactions between OA SBOs-ACCs are capable of triggering the pathological pathways leading to degenerative changes seen in the osteoarthritic joint. In conclusion, the body of work presented in this dissertation has given clear in vitro evidence that the altered bi-directional communication of SBOs and ACCs may play a role in OA development and that this process was mediated by MAPK signalling pathways. Targeting these altered interactions by the use of MAPK inhibitors may provide the scientific rationale for the development of novel therapeutic strategies in the treatment and management of OA.

Celebrity entrepreneurship and celebrity endorsement : similarities, differences and the effect of deeper engagement

Increasingly, celebrities appear not only as endorsers for products but are apparently engaged in entrepreneurial roles as initiators, owners and perhaps even managers in the ventures that market the products they promote. Despite being extensively referred to in popular media, scholars have been slow to recognise the importance of this new phenomenon. This thesis argues theoretically and shows empirically that celebrity entrepreneurs are more effective communicators than typical celebrity endorsers because of their increased engagement with ventures. I theorise that greater engagement increases the celebrity‘s emotional involvement as perceived by consumers. This is an endorser quality thus far neglected in the marketing communications literature. In turn, emotional involvement, much like the empirically established dimensions trustworthiness, expertise and attractiveness, should affect traditional outcome variables such as attitude towards the advertisement and brand. On the downside, increases in celebrity engagement may lead to relatively stronger and worsening changes in attitudes towards the brand if and when negative information about the celebrity is revealed. A series of eight experiments was conducted on 781 Swedish and Baltic students and 151 Swedish retirees. Though there were nuanced differences and additional complexities in each experiment, participants‘ reactions to advertisements containing a celebrity portrayed as a typical endorser or entrepreneur were recorded. The overall results of these experiments suggest that emotional involvement can be successfully operationalised as distinct from variables previously known to influence communication effectiveness. In addition, emotional involvement has positive effects on attitudes toward the advertisement and brand that are as strong as the predictors traditionally applied in the marketing communications literature. Moreover, the celebrity entrepreneur condition in the experimental manipulation consistently led to an increase in emotional involvement and to a lesser extent trustworthiness, but not expertise and attractiveness. Finally, negative celebrity information led to a change in participants‘ attitudes towards the brand which were more strongly negative for celebrity entrepreneurs than celebrity endorsers. In addition, the effect of negative celebrity information on a company‘s brand is worse when they support the celebrity rather than fire them. However, this effect did not appear to interact with the celebrity‘s purported engagement.

The short-term effect of air pollution on cardiovascular mortality in Tianjin, China : comparison of time series and case–crossover analyses

Background: Many studies have illustrated that ambient air pollution negatively impacts on health. However, little evidence is available for the effects of air pollution on cardiovascular mortality (CVM) in Tianjin, China. Also, no study has examined which strata length for the time-stratified case–crossover analysis gives estimates that most closely match the estimates from time series analysis. Objectives: The purpose of this study was to estimate the effects of air pollutants on CVM in Tianjin, China, and compare time-stratified case–crossover and time series analyses. Method: A time-stratified case–crossover and generalized additive model (time series) were applied to examine the impact of air pollution on CVM from 2005 to 2007. Four time-stratified case–crossover analyses were used by varying the stratum length (Calendar month, 28, 21 or 14 days). Jackknifing was used to compare the methods. Residual analysis was used to check whether the models fitted well. Results: Both case–crossover and time series analyses show that air pollutants (PM10, SO2 and NO2) were positively associated with CVM. The estimates from the time-stratified case–crossover varied greatly with changing strata length. The estimates from the time series analyses varied slightly with changing degrees of freedom per year for time. The residuals from the time series analyses had less autocorrelation than those from the case–crossover analyses indicating a better fit. Conclusion: Air pollution was associated with an increased risk of CVM in Tianjin, China. Time series analyses performed better than the time-stratified case–crossover analyses in terms of residual checking.

Social clubs and social capital : the effect of electronic gaming machines in disadvantaged regions on the creation or destruction of community resilience

The role of particular third sector organisations, Social Clubs, in supporting gambling through the use of EGMs in venues presents as a difficult social issue. Social Clubs gain revenue from gambling activities; but also contribute to social well-being through the provision of services to communities. The revenues derived from gambling in specific geographic locales has been seen by government as a way to increase economic development particularly in deprived areas. However there are also concerns about accessibility of low-income citizens to Electronic Gaming Machines (EGMS) and the high level of gambling overall in these deprived areas. We argue that social capital can be viewed as a guard against deleterious effects of unconstrained use of EGM gambling in communities. However, it is contended that social capital may also be destroyed by gambling activity if commercial business actors are able to use EGMs without community obligations to service provision. This paper examines access to gambling through EGMs and its relationship to social capital and the consequent effect on community resilience, via an Australian case study. The results highlight the potential two-way relationship between gambling and volunteering, such that volunteering (and social capital more generally) may help protect against problems of gambling, but also that volunteering as an activity may be damaged by increased gambling activity. This suggests that, regardless of the direction of causation, it is necessary to build up social capital via volunteering and other social capital activities in areas where EGMS are concentrated. The study concludes that Social Clubs using EGMs to derive funds are uniquely positioned within the community to develop programs that foster social capital creation and build community resilience in deprived areas.

Effect of acupressure on thirst in hemodialysis patients

Background: Thirst and dry mouth are common among hemodialysis (HD) patients. This paper reports a study to evaluate the impact of an acupressure program on HD patients’ thirst and salivary flow rates. Methods: The acupressure program included placebo, followed by true acupressure each applied for 4 weeks. Twenty-eight patients (mean age 57.6, SD = 16.13 years) first received a sticker as placebo acupressure at two acupoints CV23 and TE17 three times a week for 4 weeks, and then received true acupressure in the same area for the next 4 weeks. Salivary flow rate and thirst intensity were measured at baseline, during and after treatment completion for both the placebo and true acupressure program. Results: The true acupressure program was associated with significantly increased salivary flow rate (0.09 ± 0.08 ml/min at baseline to 0.12 ± 0.08 ml/min after treatments completion, p = 0.04). The mean thirst intensity also improved from 4.21 ± 2.66 at baseline to 2.43 ± 2.32 (p = 0.008) after treatment completion in HD patients. There was no statistically significant difference in pre-post program salivary flow rate; however, significant improvement in thirst intensity scores was observed (p = 0.009) in the placebo acupressure program. Conclusion: This study provides preliminary evidence that acupressure may be effective in improving salivary flow rates and thirst intensity.

The effect of metamictization on the Raman spectroscopy of the uranyl titanate mineral davidite (La,Ce)(Y,U,Fe2+)(Ti,Fe3+)20(O,OH)38

Raman spectra of the uranyl titanate mineral davidite-(La) (La,Ce)(Y,U,Fe2+)(Ti,Fe3+)20(O,OH)38 were analysed and related to the mineral structure. Observed bands are attributed to the TiO and (UO2)2+ stretching and bending vibrations, U-OH bending vibrations, H2O and (OH)- stretching, bending and libration modes. U-O bond lengths in uranyls and O-H…O bond lengths are calculated from the wavenumbers assigned to the stretching vibrations. Raman bands of davidite-(La) are in harmony with those of the uranyl oxyhydroxides. The mineral davidite-(La) is metamict as is evidenced by the intensity of the UO stretching and bending modes being of lower intensity than expected and with bands that are significantly broader.