Phenothiazine UVA dosimeter : characteristics and performance

This paper provides an overview of the characteristics of a phenothiazine-mylar dosimeter which can be used as an effective solar UVA exposure assessment tool. This dosimeter is sensitive to UVA wavelengths (315–400 nm); its performance has been characterized in a series of tests such as (a) UVA exposure response (dose-response), (b) temperature stability of the response, (c) impact of long term storage, and (d) angular response. There is no effect of long term storage post-exposure and no effect of temperature up to 30 °C. For angles up to 70°, the cosine error of the normalized UVA is less than approximately 0.1. These characterizations have confirmed the reliability and reproducibility of a phenothiazine-mylar combined dosimeter as an effective solar UVA exposure tool for field-based studies of the UVA exposures to population groups.

Combining expert opinions in prior elicitation

A method of eliciting prior distributions for Bayesian models using expert knowledge is proposed. Elicitation is a widely studied problem, from a psychological perspective as well as from a statistical perspective. Here, we are interested in combining opinions from more than one expert using an explicitly model-based approach so that we may account for various sources of variation affecting elicited expert opinions. We use a hierarchical model to achieve this. We apply this approach to two problems. The first problem involves a food risk assessment problem involving modelling dose-response for Listeria monocytogenes contamination of mice. The second concerns the time taken by PhD students to submit their thesis in a particular school.

Glycosaminoglycan and growth factor mediated murine calvarial cell proliferation

Understanding the complex mechanisms underlying bone remodeling is crucial to the development of novel therapeutics. Glycosaminoglycans (GAGs) localised to the extracellular matrix (ECM) of bone are thought to play a key role in mediating aspects of bone development. The influence of isolated GAGs was studied by utilising in vitro murine calvarial monolayer and organ culture model systems. Addition of GAG preparations extracted from the cell surface of human osteoblasts at high concentrations (5 microg/ml) resulted in decreased proliferation of cells and decreased suture width and number of bone lining cells in calvarial sections. When we investigated potential interactions between the growth factors fibroblast growth factor-2 (FGF2), bone morphogenic protein-2 (BMP2) and transforming growth factor-beta1 (TGFbeta1) and the isolated cell surface GAGs, differences between the two model systems emerged. The cell culture system demonstrated a potentiating role for the isolated GAGs in the inhibition of FGF2 and TGFbeta1 actions. In contrast, the organ culture system demonstrated an enhanced stimulation of TFGbeta1 effects. These results emphasise the role of the ECM in mediating the interactions between GAGs and growth factors during bone development and suggest the GAG preparations contain potent inhibitory or stimulatory components able to mediate growth factor activity.

A forced titration study of the antioxidant and immunomodulatory effects of Ambrotose AO supplement

Background Oxidative stress plays a role in acute and chronic inflammatory disease and antioxidant supplementation has demonstrated beneficial effects in the treatment of these conditions. This study was designed to determine the optimal dose of an antioxidant supplement in healthy volunteers to inform a Phase 3 clinical trial. Methods The study was designed as a combined Phase 1 and 2 open label, forced titration dose response study in healthy volunteers (n = 21) to determine both acute safety and efficacy. Participants received a dietary supplement in a forced titration over five weeks commencing with a no treatment baseline through 1, 2, 4 and 8 capsules. The primary outcome measurement was ex vivo changes in serum oxygen radical absorbance capacity (ORAC). The secondary outcome measures were undertaken as an exploratory investigation of immune function. Results A significant increase in antioxidant activity (serum ORAC) was observed between baseline (no capsules) and the highest dose of 8 capsules per day (p = 0.040) representing a change of 36.6%. A quadratic function for dose levels was fitted in order to estimate a dose response curve for estimating the optimal dose. The quadratic component of the curve was significant (p = 0.047), with predicted serum ORAC scores increasing from the zero dose to a maximum at a predicted dose of 4.7 capsules per day and decreasing for higher doses. Among the secondary outcome measures, a significant dose effect was observed on phagocytosis of granulocytes, and a significant increase was also observed on Cox 2 expression. Conclusion This study suggests that Ambrotose AO® capsules appear to be safe and most effective at a dosage of 4 capsules/day. It is important that this study is not over interpreted; it aimed to find an optimal dose to assess the dietary supplement using a more rigorous clinical trial design. The study achieved this aim and demonstrated that the dietary supplement has the potential to increase antioxidant activity. The most significant limitation of this study was that it was open label Phase 1/Phase 2 trial and is subject to potential bias that is reduced with the use of randomization and blinding. To confirm the benefits of this dietary supplement these effects now need to be demonstrated in a Phase 3 randomised controlled trial (RCT).

p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas

Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors.

Drinking and driving in Vietnam : perceptions and risk

Road traffic injuries are a major global public health problem but continue to receive inadequate attention. Alcohol influences both risk and consequence of road traffic injury but the scale of the problem is not well understood in many countries. In Vietnam, economic development has brought a substantial increase in the number of registered motorcycles as well as alcohol consumption. Traffic injury is among the leading causes of death in Vietnam but there is little local information regarding alcohol related traffic injuries. The primary goal of this study is to explore the drinking and driving patterns of males and their perceptions towards drink-driving and to determine the relationship between alcohol consumption and road traffic injuries. Furthermore, this thesis aims to present the situation analysis for choosing priority actions to reduce drinking and driving in Vietnam. The study is a combination of two cross-sectional surveys and a pilot study. The pilot study, involving 224 traffic injured patients, was conducted to test the tools and the feasibility of approach methods. In the first survey, male patrons (n=464) were randomly selected at seven restaurants. Face-to-face interviews were conducted when patrons just arrived and breath tests were collected when they were about to leave the restaurant. In the second survey, male patients admitted to hospital following a traffic injury (n=480, of which 414 were motorcycle or bicycle riders) were interviewed and their blood alcohol concentration (BAC) measured by breathalyzer. The results show broadly similar patterns of drinking and driving among male patrons and male traffic injured patients with a high frequency of drinking and drink-driving reported among the majority of the two groups. A high proportion of male patrons were leaving restaurants with a BAC over the legal limit. Factors that significantly associate with the number of drinks and BAC were age, hazardous drinking, frequency of drink-driving in the past year, self-estimated number of drinks consumed to drive legally, perceived family’s disapproval of drink-driving, and perceived legal risk and physical risk. The proportion of patrons and patients with BAC above the legal limit of 0.05 were 86.7% and 60.4% respectively, which was much higher than found in previous studies. In addition, both groups had a high prevalence of BAC over 0.15g/100ml (39.7% of patrons and 45.6% patients), a level that can seriously affect driving capacity. Results from the case-crossover analysis for patients indicate a dose-response relationship between alcohol consumption and the risk of traffic injury. The risk of traffic injury increased when alcohol was consumed before driving and there was a more than 13 fold increase when six or more drinks were consumed. Regarding perceptions towards drinking and driving, findings corroborate the low awareness among males in Vietnam, with a majority of respondents holding a low knowledge of safe and legally permissible alcohol use, and a low perceived risk of drinking and driving. The results also indicate a huge gap in prevention skills in terms of planning ahead or using alternative transport to avoid drink-driving and a perception by patrons and patients of a low rate of disapproval of drink-driving from peers and family. Findings in this study have considerable implications for national policy, injury prevention, clinical practice, reporting systems, and for further research. The low rate of compliance with existing laws and a generally low perceived legal risk toward drink-driving in this study call for the strengthening of enforcement along with mass media campaigns and news coverage in order to decrease the widespread perception of impunity and thereby, to reduce the level of drink-driving. In addition, no significant difference was found in this study on risk of traffic injuries between car drivers and motorcycle drivers. The current inconsistency between legal BAC for drivers of motorcycles, compared to cars, thus needs addressing. Furthermore, as drinking was found to be very common, rather than solely targeting drink-driving, it is important to call for a more strategic and comprehensive approach to alcohol policy in Viet Nam. This study also has considerable implications for clinical practice in terms of screening and brief interventions. Our study suggests that the short form of the AUDIT (AUDIT-C) screening tool is appropriate for use in busy emergency departments. The high proportion of traffic injured patients with evidence of alcohol abuse or hazardous drinking suggests that brief interventions by alcohol and drug counselors in emergency departments are a sensible option to addressing this important problem. The significance of this study is in the combination of the systematic collection of breath test and use of case-crossover design to estimate the risk of traffic injuries after alcohol consumption. The results provide convincing evidence to policy makers, health authorities and the media to help raise community awareness and policy advocacy toward the drinkdriving problem in Vietnam. The findings suggest an urgent need for a multi-sectoral approach to curtail drink-driving in Vietnam, especially programs to raise community awareness and effective legal enforcement. Furthermore, serving as a situation analysis, the thesis should inform the formulation of interventions designed to curtail drinking and driving in Vietnam and other developing countries.

Probiotics, immunity and exercise : a review

Nutritional practices that promote good health and optimal athletic performance are of interest to athletes, coaches, exercise scientists and dietitians. Probiotic supplements modulate the intestinal microbial flora and offer promise as a practical means of enhancing gut and immune function. The intestinal microbial flora consists of diverse bacterial species that inhabit the gastrointestinal tract. These bacteria are integral to the ontogeny and regulation of the immune system, protection of the body from injection, and maintenance of intestinal homeostasis. The interaction of the gut microbial flora with intestinal epithelial cells and immune cells exerts beneficial effects on the upper respiratory tract, skin and uro-genital tract. The capacity for probiotics to modulate perturbations in immune function after exercise highlight their potential for use in individuals exposed to high degrees of physical and environment stress. Future studies are required to address issues of dose-response in various exercise settings, the magnitude of species-specific effects, mechanisms of action and clinical outcomes in terms of health and performance.

Estimating health related costs and savings from balcony acoustic design for road traffic noise

A multi-faceted study is conducted with the objective of estimating the potential fiscal savings in annoyance and sleep disturbance related health costs due to providing improved building acoustic design standards. This study uses balcony acoustic treatments in response to road traffic noise as an example. The study area is the State of Queensland in Australia, where regional road traffic noise mapping data is used in conjunction with standard dose–response curves to estimate the population exposure levels. The background and the importance of using the selected road traffic noise indicators are discussed. In order to achieve the objective, correlations between the mapping indicator (LA10 (18 hour)) and the dose response curve indicators (Lden and Lnight) are established via analysis on a large database of road traffic noise measurement data. The existing noise exposure of the study area is used to estimate the fiscal reductions in health related costs through the application of simple estimations of costs per person per year per degree of annoyance or sleep disturbance. The results demonstrate that balcony acoustic treatments may provide a significant benefit towards reducing the health related costs of road traffic noise in a community.

Quantitative evaluation of polymer gel dosimeters by broadband ultrasound attenuation

Ultrasound has been examined previously as an alternative readout method for irradiated polymer gel dosimeters, with authors reporting varying dose response to ultrasound transmission measurements. In this current work we extend previous work to measure the broadband ultrasound attenuation (BUA) response of irradiated PAGAT gel dosimeters, using a novel ultrasound computed tomography system.

Children exposure assessment to ultrafine particles and black carbon: The role of transport and cooking activities

An accurate evaluation of the airborne particle dose-response relationship requires detailed measurements of the actual particle concentration levels that people are exposed to, in every microenvironment in which they reside. The aim of this work was to perform an exposure assessment of children in relation to two different aerosol species: ultrafine particles (UFPs) and black carbon (BC). To this purpose, personal exposure measurements, in terms of UFP and BC concentrations, were performed on 103 children aged 8-11 years (10.1 ± 1.1 years) using hand-held particle counters and aethalometers. Simultaneously, a time-activity diary and a portable GPS were used to determine the children’s daily time-activity pattern and estimate their inhaled dose of UFPs and BC. The median concentration to which the study population was exposed was found to be comparable to the high levels typically detected in urban traffic microenvironments, in terms of both particle number (2.2×104 part. cm-3) and BC (3.8 μg m-3) concentrations. Daily inhaled doses were also found to be relatively high and were equal to 3.35×1011 part. day-1 and 3.92×101 μg day-1 for UFPs and BC, respectively. Cooking and using transportation were recognized as the main activities contributing to overall daily exposure, when normalized according to their corresponding time contribution for UFPs and BC, respectively. Therefore, UFPs and BC could represent tracers of children exposure to particulate pollution from indoor cooking activities and transportation microenvironments, respectively.

Metrological performances of a diffusion charger particle counter for personal monitoring

Airborne particles have been shown to be associated with a wide range of adverse health effects, which has led to a recent increase in medical research to gain better insight into their health effects. However, accurate evaluation of the exposure-dose-response relationship is highly dependent on the ability to track actual exposure levels of people to airborne particles. This is quite a complex task, particularly in relation to submicrometer and ultrafine particles, which can vary quite significantly in terms of particle surface area and number concentrations. Therefore, suitable monitors that can be worn for measuring personal exposure to these particles are needed. This paper presents an evaluation of the metrological performance of six diffusion charger sensors, NanoTracer (Philips Aerasense) monitors, when measuring particle number and surface area concentrations, as well as particle number distribution mean when compared to reference instruments. Tests in the laboratory (by generating monodisperse and polydisperse aerosols) and in the field (using natural ambient particles) were designed to evaluate the response of these devices under both steady-state and dynamics conditions. Results showed that the NanoTracers performed well when measuring steady state aerosols, however they strongly underestimated actual concentrations during dynamic response testing. The field experiments also showed that, when the majority of the particles were smaller than 20 nm, which occurs during particle formation events in the atmosphere, the NanoTracer underestimated number concentration quite significantly. Even though the NanoTracer can be used for personal monitoring of exposure to ultrafine particles, it also has limitations which need to be considered in order to provide meaningful results.

Clinical outcomes of vitamin D deficiency and supplementation in cancer patients

Results of recent studies suggest that circulating levels of vitamin D may play an important role in cancer-specific outcomes. The present systematic review was undertaken to determine the prevalence of vitamin D deficiency (<25 nmol/L) and insufficiency (25-50 nmol/L) in cancer patients and to evaluate the association between circulating calcidiol (the indicator of vitamin D status) and clinical outcomes. A systematic search of original, peer-reviewed studies on calcidiol at cancer diagnosis, and throughout treatment and survival, was conducted yielding 4,706 studies. A total of 37 studies met the inclusion criteria for this review. Reported mean blood calcidiol levels ranged from 24.7 to 87.4 nmol/L, with up to 31% of patients identified as deficient and 67% as insufficient. The efficacy of cholecalciferol supplementation for raising the concentration of circulating calcidiol is unclear; standard supplement regimens of <1,000 IU D3 /day may not be sufficient to maintain adequate concentrations or prevent decreasing calcidiol. Dose-response studies linking vitamin D status to musculoskeletal and survival outcomes in cancer patients are lacking.

The effect of olive leaf extract on platelet function

Background Epidemiological studies have shown a reduced incidence of cardiovascular disease in the Mediterranean population attributed to the consumption of dietary olive oil rich in antioxidants. This has lead to increased interest in the antioxidant properties of other phenolic compounds of olive tree products. It has been suggested that olive leaf extract may also have health benefits due to its antioxidant and anti-inflammatory activities. Antioxidants can prevent the effects of oxidative metabolism by scavenging free radicals and decreasing the hyperactivity of platelets associated with the development of occlusive thrombosis. No studies to date have investigated the effects of olive leaf extract on platelet function to our knowledge. Improved understanding of the antioxidant properties of olive leaf extract and its effect on platelet function could lead to improved cardiovascular health. Objective The current study used an olive leaf extract prepared from the Olea europaea L. tree. The aim was to determine if polyphenols in olive leaf extract would reduce platelet activity and, to establish an optimal dose in vitro that would reduce platelet aggregation and ATP release. Design Eleven subjects with normal platelet counts (150–400 x 109/L) were recruited for the current in vitro study. Olive leaf extract was added to citrated whole blood to obtain five concentrations ranging from 5.4 ug/mL to 54.0 ug/mL for a dose response curve. Baseline samples, without olive leaf extract were used as a negative control for each subject. After 2 hours incubation with olive leaf extract samples were analyzed for platelet aggregation and ATP release from platelets stimulated by the addition of collagen. Results Whole blood analysis (n=11) showed a clear dose-dependant reduction in platelet aggregation with the increasing olive leaf extract concentrations (p<0.0001). There was also a similar decrease in ATP release from collagen stimulated platelets (p=0.02). Conclusion In the current study the olive leaf extract obtained from Olea europaea L. inhibited platelet aggregation and ATP release from collagen stimulated platelets in vitro. This study suggests olive leaf extract may prevent occlusive thrombosis by reducing platelet hyperactivity.

Low formalin concentrations induce fine-tuned responses that are sex and age-dependent : a developmental study

The formalin test is increasingly applied as a model of inflammatory pain using high formalin concentrations (5–15%). However, little is known about the effects of low formalin concentrations on related behavioural responses. To examine this, rat pups were subjected to various concentrations of formalin at four developmental stages: 7, 13, 22, and 82 days of age. At postnatal day (PND) 7, sex differences in flinching but not licking responses were observed with 0.5% formalin evoking higher flinching in males than in females. A dose response was evident in that 0.5% formalin also produced higher licking responses compared to 0.3% or 0.4% formalin. At PND 13, a concentration of 0.8% formalin evoked a biphasic response. At PND 22, a concentration of 1.1% evoked higher flinching and licking responses during the late phase (10–30 min) in both males and females. During the early phase (0–5 min), 1.1% evoked higher licking responses compared to 0.9% or 1% formalin. 1.1% formalin produced a biphasic response that was not evident with 0.9 or 1%. At PND 82, rats displayed a biphasic pattern in response to three formalin concentrations (1.25%, 1.75% and 2.25%) with the presence of an interphase for both 1.75% and 2.25% but not for 1.25%. These data suggest that low formalin concentrations induce fine-tuned responses that are not apparent with the high formalin concentration commonly used in the formalin test. These data also show that the developing nociceptive system is very sensitive to subtle changes in formalin concentrations.

Quantitative ultrasound computed tomography imaging of PAGAT radiation dosimetry gel

This research developed and scientifically validated a new ultrasound transmission computed tomography system with the aim of quantitative assessment of a polymer gel dosimeter including dose response verification of ultrasonic parameters of attenuation, velocity and broadband ultrasound attenuation (BUA). This work was the first to investigate and report ultrasound frequency dependent attenuation in a gel dosimeter, demonstrating a dose dependence.