Per- and poly-fluoroalkyl substances (PFASs) in follicular fluid from women experiencing infertility in Australia.

Per- and poly-fluoroalkyl substances (PFASs) have been widely used and detected in human matrices. Evidence that PFAS exposure may be associated with adverse human reproductive health effects exists, however, data is limited. The use of a human matrix such as follicular fluid to determine chemical exposure, along with reproductive data will be used to investigate if there is a relationship between PFAS exposure and human fertility. OBJECTIVE: This study aims to: (1) assess if associations exist between PFAS concentrations and/or age and fertilisation rate (as determined in follicular fluid of women in Australia who received assisted reproductive treatment (ART)); and (2) assess if associations exist between PFAS concentrations and infertility aetiology. METHODS: Follicular fluids were originally collected from participants who underwent fully stimulated ART treatment cycles at an in vitro fertilisation (IVF) clinic in the period 2006-2009 and 2010-11 in Queensland, Australia. The samples were available for analysis of 32 PFASs including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) using high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). 97 samples were matched with limited demographic data (age and fertilisation rate) and five infertility factors (three known female factors): 1) endometriosis, 2) polycystic ovarian syndrome (PCOS), and 3) genital tract infections - tubal/pelvic inflammation disease; as well as 4) male factor, and 5) idiopathic or unknown from either males or females. SPSS was used for linear regression analysis. RESULTS: PFASs were detected in all follicular fluid samples with the mean concentrations of PFOS and PFOA, 4.9, and 2.4 ng/ml, respectively. A lower fertilisation rate was observed at higher age when age was added as a covariate, but there was no relationship between PFAS concentrations and fertilisation rate. There were few statistically significant associations between PFAS concentrations in follicular fluid and infertility factors. Log-transformed PFHxS concentrations were lower in females with endometriosis (factor 1) than in women who had reported 'male factors' as a reason of infertility, while PFHpA was higher in women who had infertile due to female factors (factor 1-3) compared to those who had infertile due to male factor. CONCLUSION: PFASs were detected in follicular fluid of Australian women who had been treated at an IVF clinic. PFAS exposure found in follicular fluids is linked to increased risk of some infertility factors, and increased age was associated with decreased fertilisation rate in our data. But there was no relationship between PFAS and ferlitisation rate. Further large-scale investigations of PFAS and health effects including infertility are warranted.

A systematic review: Impact of endocrine disrupting chemicals exposure on fecundity as measured by time to pregnancy.

BACKGROUND: Emerging scientific evidence suggests that exposure to environmental pollutants is associated with negative effects on fecundity as measured by time to pregnancy (TTP). OBJECTIVES: To conduct a systematic review of the literature on the association between selected endocrine disrupting chemicals (EDCs), and fecundity as measured by TTP in humans. Compounds included in this review are: brominated flame retardants (BFRs) such as hexabromocyclododecane, tetrabromobiphenol A and polybrominated diphenyl ethers; organophosphates flame retardants (OPFRs); and phthalates. METHODS: Scopus, MEDLINE via Ebscohost and EMBASE databases were searched for articles exploring the relationships between selected EDCs and fecundity as measured by time to pregnancy. We assessed the quality of included studies and evidence for causality was graded using the criteria developed by the World Cancer Research Fund. RESULTS: 14 studies of 191 full-text articles assessed for eligibility were included for qualitative synthesis. Five studies examined BFRs and 10 studies examined phthalates. Among the fourteen, one study assessed both BFRs and phthalates. There were no studies which investigated fecundity as measured by TTP on HBCD, TBBPA, or OPFRs. We recorded plausible fecundity outcomes as measured by TTP related to some of these EDCs. BFRs or phthalates increased TTP. However, results were inconsistent. CONCLUSION: We recorded mostly weak associations between exposure to selected EDCs and fecundity. However, evidence was considered limited to conclude a causal relationship due to inconsistency of results. The health risks posed by these chemicals in exposed populations are only beginning to be recognized and prospective measurement of the environmental effects of the chemicals in large cohort studies are urgently needed to confirm these relationships and inform policies aimed at exposure prevention.

Demographic and temporal trends of hexabromocyclododecanes (HBCDD) in an Australian population.

Hexabromocyclododecanes (HBCDD) were measured in 67 pooled serum samples collected between 2002 and 2015 in South East Queensland, Australia. These data are the first report of HBCDD in Australian human serum. Temporal and demographic (age and gender) trends were investigated. HBCDD were detected in measurable concentrations in 69% of samples. The average ∑HBCDD concentration was 3.1ng/g lipid, whilst the range was <0.5 to 36ng/g lipid. α-HBCDD was the dominant stereoisomer making up an average of 60% of ∑HBCDD. The remainder was made up by γ-HBCDD. In contrast to another group of brominated flame retardants (BFRs, (polybrominated diphenyl ethers (PBDEs)), HBCDD were found in the lowest concentrations in pools from children aged 0-4 years. This could be attributed to differences in exposure, usage, and/ or the much lower half-life of HBCDD in the human body compared to PBDEs. HBCDD concentrations appear to be significantly higher in females than in males, however the reasons for this are unclear.

Concentrations of organochlorine pesticides in pooled human serum by age and gender.

Organochlorine pesticides (OCPs) have been used for many decades in Australia with cessation of selected persistent and bioaccumulative OCPs ranging from the 1970s to as recently as 2007. The specific aims of this study were to use samples representative of an Australian population to assess age and gender differences in the concentration of OCPs in human blood sera and to investigate temporal trends in these chemicals. Serum was collected from de-identified, surplus pathology samples over five time periods (2002/03, 2006/07, 2008/09, 2010/11 and 2012/13), with 183 serum pools made from 12,175 individual samples; 26 pools in 2002/03, 85 pools in 2006/07 and 24 pools each in 2008/09, 2010/11 and 2012/13. Samples were analyzed for hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH), γ -hexachlorocyclohexane (lindane) (γ-HCH), oxy-chlordane, trans-nonachlor, p,p'-DDE, o,p'-DDT, p,p'-DDT and Mirex. Stratification criteria included gender and age (0-4; 5-15; 16-30; 31-45; 46-60; and >60 years) with age additionally stratified by adults >16 years and children 0-4 and 5-15 years. All pools from all collection periods had detectable concentrations of OCPs with a detection frequency of >60% for HCB, ß-HCH, trans-nonachlor, p,p'-DDT and p,p'-DDE. The overall OCP concentrations increased with age with the highest concentrations in the >60 years groups. Females did not have higher mean OCP concentrations than males except for HCB concentrations (p=0.0006). Temporal trends showed overall decreasing serum concentrations by collection period with the exception of an increase in OCP concentrations between 2006/07 and 2008/09. Excluding this data point, HCB decreased from year to year by 7-76%; ß-HCH concentrations decreased by 14 - 38%; trans-nonachlor concentrations decreased by 10 - 65%; p,p'-DDE concentrations decreased by 6 - 52%; and p,p'-DDT concentrations decreased by 7 - 30%. The results indicate that OCP concentrations have decreased over time as is to be expected following the phase out of these chemicals in Australia.

Polybrominated diphenyl ethers (PBDEs) in dust from primary schools in South East Queensland, Australia.

PBDE concentrations are higher in children compared to adults with exposure suggested to include dust ingestion. Besides the home environment, children spend a great deal of time in school classrooms which may be a source of exposure. As part of the "Ultrafine Particles from Traffic Emissions and Children's Health (UPTECH)" project, dust samples (n=28) were obtained in 2011/12 from 10 Brisbane, Australia metropolitan schools and analysed using GC and LC-MS for polybrominated diphenyl ethers (PBDEs) -17, -28, -47, -49, -66, -85, -99, -100, -154, -183, and -209. Σ11PBDEs ranged from 11-2163 ng/g dust; with a mean and median of 600 and 469 ng/g dust, respectively. BDE-209 (range n.d. -2034 ng/g dust; mean (median) 402 (217)ng/g dust) was the dominant congener in most classrooms. Frequencies of detection were 96%, 96%, 39% and 93% for BDE-47, -99, -100 and -209, respectively. No seasonal variations were apparent and from each of the two schools where XRF measurements were carried out, only two classroom items had detectable bromine. PBDE intake for 8-11 year olds can be estimated at 0.094 ng/day BDE-47; 0.187 ng/day BDE-99 and 0.522ng/day BDE-209 as a result of ingestion of classroom dust, based on mean PBDE concentrations. The 97.5% percentile intake is estimated to be 0.62, 1.03 and 2.14 ng/day for BDEs-47, -99 and -209, respectively. These PBDE concentrations in dust from classrooms, which are higher than in Australian homes, may explain some of the higher body burden of PBDEs in children compared to adults when taking into consideration age-dependant behaviours which increase dust ingestion.

Sustainability of Public Health Interventions to Reduce the Risk of Dioxin Exposure at Severe Dioxin Hot Spots in Vietnam.

Severe dioxin contamination at Bien Hoa and Da Nang airbases, Vietnam is of international concern. Public Health risk reduction programs were implemented in Bien Hoa in 2007-2009 and in Da Nang in 2009-2011. In 2009 and 2011 we reported the encouraging results of these interventions in improving the knowledge, attitude and practices (KAP) of local residents in reducing the dioxin exposure risk through foods. In 2013 we revisited these dioxin hot spots, aimed to evaluate whether the results of the intervention were maintained and to identify factors affecting the sustainability of the programs. To assess this, 16 in-depth interviews, six focus group discussions, and pre and post intervention KAP surveys were undertaken. 800 respondents from six intervention wards and 200 respondents from Buu Long Ward (the control site) were randomly selected to participate in the surveys. The results showed that as of 2013, the programs were rated as "moderately sustained" with a score of 3.3 out of 5.0 (cut off points 2.5 to <3.5) for Bien Hoa, and "well sustained" with a score of 3.8 out of 5.0 (cut off points 3.5 to <4.5) for Da Nang. Most formal intervention program activities had ceased and dioxin risk communication activities were no longer integrated into local routine health education programs. However, the main outcomes were maintained and were better than that in the control ward. Migration, lack of official guidance from City People's Committees and local authorities as well as the politically sensitive nature of dioxin issues were the main challenges for the sustainability of the programs.

Serum elimination half-lives adjusted for ongoing exposure of tri-to hexabrominated diphenyl ethers: Determined in persons moving from North America to Australia.

The objective of the study was to determine the human serum elimination half-life of polybrominated diphenyl ethers (PBDEs) adjusted for ongoing exposure in subjects moving from a higher exposure region (North America) to a lower exposure region (Australia). The study population was comprised of exchange students and long-term visitors from North America moving to Brisbane, Australia (N = 27) and local residents (N = 23) who were followed by repeated serum sampling every other month. The local residents were sampled to adjust for ongoing exposure in Australia. Only one visitor remained in Australia for a period of time similar to the elimination half-life and had a sufficiently high initial concentration of PBDEs to derive a half-life. This visitor arrived in Australia in March of 2011 and remained in the country for 1.5 years. Since the magnitude of PBDE exposure is lower in Australia than in North America we observed an apparent 1st order elimination curve over time from which we have estimated the serum elimination half-lives for BDE28, BDE47, BDE99, BDE100, and BDE153 to be 0.942, 1.19, 1.03, 2.16, and 4.12 years, respectively. Uncertainty in the estimates were estimated using a Monte Carlo simulation. The human serum elimination half-life adjusted for ongoing exposure can allow us to assess the effectiveness and reduction in exposure in the general population following phase out of commercial penta- and octaBDE in 2004 in the United States.

Bayesian Approach to Predicting Acute Appendicitis Using Ultrasonographic and Clinical Variables in Children.

OBJECTIVES: Ultrasound has an established role in the diagnostic pathway for children with suspected appendicitis. Relevant clinical information can influence the diagnostic probability and reporting of ultrasound findings. A Bayesian network (BN) is a directed acyclic graph (DAG) representing variables as nodes connected by directional arrows permitting visualisation of their relationships. This research developed a BN model with ultrasonographic and clinical variables to predict acute appendicitis in children. METHODS: A DAG was designed through a hybrid method based on expert opinion and a review of literature to define the model structure; and the discretisation and weighting of identified variables were calculated using principal components analysis, which also informed the conditional probability table of nodes. RESULTS: The acute appendicitis target node was designated as an outcome of interest influenced by four sub-models, including Ultrasound Index, Clinical History, Physical Assessment, and Diagnostic Tests. These sub-models included four sonographic, three blood-test, and six clinical variables. The BN was scenario tested and evaluated for face, predictive, and content validity. A lack of similar networks complicated concurrent and convergent validity evaluation. CONCLUSIONS: To our knowledge, this is the first BN model developed for the identification of acute appendicitis incorporating imaging variables. It has particular benefit for cases in which variables are missing because prior probabilities are built into corresponding nodes. It will be of use to clinicians involved in ultrasound examination of children with suspected appendicitis, as well as their treating clinicians. Prospective evaluation and development of an online tool will permit validation and refinement of the BN.

Improving the value of ultrasound in children with suspected appendicitis: a prospective study integrating secondary sonographic signs.

PURPOSE: The purpose of this study was to determine whether the awareness and inclusion of secondary sonographic signs of appendicitis, in combination with a structured evaluation as part of engagement and training for sonographers, improved appendix visualization rates and reduced equivocal findings in children with suspected acute appendicitis. METHODS: This was a prospective study of 230 children at a tertiary children's hospital in Australia referred for an ultrasound examination of suspected appendicitis. The ultrasound findings, radiology reports, histology, clinical results, and follow-up were collated. Secondary signs were used as an additional assessment of the likelihood of disease where possible, even in the absence of an identified appendix. RESULTS: The implementation of a structured evaluation as part of sonographer engagement and training resulted in a 28% improvement in appendix visualization (68.7%) compared with a prior retrospective study in a similar population (40.7%). The diagnostic accuracy was 91.7%, with likelihood ratios suggesting a meaningful influence of the pre-test probability of appendicitis in children studied (positive likelihood ratio, 11.22; negative likelihood ratio, 0.09.). Only 7.8% of the findings were equivocal. A binary 6-mm diameter cut-off did not account for equivocal cases, particularly lymphoid hyperplasia. CONCLUSION: Engagement of sonographers performing pediatric appendiceal ultrasound through training in the scanning technique and awareness of secondary signs significantly improved the visualization rate and provided more meaningful findings to referrers.

Human biomonitoring in Australian children: Brominated flame retardants decrease from 2006 to 2015.

Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD) were used intensively as flame retardants, worldwide. They have been detected in human serum samples and PBDEs have been found to be elevated in young children. Commercial Penta- and Octa-PBDE mixtures were banned in Australia in 2005, while HBCDD was banned worldwide in 2013. We investigated PBDE and HBCDD concentrations in serum collected from young children. We also investigated temporal trends in PBDE concentration 10 years after their Australian ban. Surplus human blood serum samples were collected through a pathology clinic (n = 800), in 2014/15, stratified by age (0-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-42, 42-48, 48-54 and 54-60 months) and sex and pooled for analysis of PBDEs (BDEs -28, -47, -99, -100, -153, -154, -183) and HBCDD. In 2014/15, the geometric mean concentration of the sum of all PBDEs measured (ΣPBDEs) was 4.5 ng/g lipid (median: 4.6 ng/g lipid, range: 0.88-26 ng/g lipid). A positive association between BDE-47 concentration and age was observed (R = 0.41, p = 0.008), however there were no trends between other PBDE congeners or HBCDD and age. There were no significant differences between genders for PBDEs (t-test, p = 0.802) or HBCDD (t-test, p = 0.740).The highest concentrations observed were in pools from the females 30-36 month (26 ng/g lipid) and Males 6-12 month (21 ng/g lipid) categories. BDEs -47 and -99 were the predominant congeners with a combined average contribution of 75% of ΣPBDEs. PBDEs showed a significant reduction in children aged 0-4 years over an eight year period. In 2014/15, the mean (range) concentration of BDE-47 is 2.8 (0.23 to 11) ng/g lipid compared to pools in 2006/07 at 19 (3-55) ng/g lipid (p < 0.0001) and for BDE-153 is 0.73 (<0.1 = -2.9) ng/g lipid compared to pools in 2006/07 at 4.7 (2-10) ng/g lipid (p < 0.0001). HBCDD concentrations were lower than PBDEs with a mean concentration of 0.45 ng/g lipid. There were no temporal trends observed for HBCDD when compared to samples collected in 2012. The dominant stereoisomer was α-HBCDD (mean = 0.38 ng/g lipid) with an average contribution of 65% towards ΣHBCDD. Levels of PBDEs in young Australian children have significantly decreased since the bans of commercial Penta- and Octa-BDE in 2005. There has been no observed decrease in HBCDD levels in Australian children since its ban in 2012.

The influence of age and gender on triclosan concentrations in Australian human blood serum.

The bactericide triclosan has found wide-spread use in e.g. soaps, deodorants and toothpastes. Recent in vitro and in vivo studies indicate that triclosan might exert adverse effects in humans. Triclosan has previously been shown to be present in human plasma and milk at concentrations that are well correlated to the use of personal care products containing triclosan. In this study we investigated the influence of age, gender, and the region of residence on triclosan concentrations in pooled samples of Australian human blood serum. The results showed no influence of region of residence on the concentrations of triclosan. There was a small but significant influence of age and gender on the serum triclosan concentrations, which were higher in males than in females, and highest in the group of 31-45 year old males and females. However, overall there was a lack of pronounced differences in the triclosan concentrations within the dataset, which suggests that the exposure to triclosan among different groups of the Australian population is relatively homogenous. A selection of the dataset was compared with previous measurements of triclosan concentrations in human plasma from Sweden, where the use of triclosan is expected to be low due to consumer advisories. The triclosan concentrations were a factor of 2 higher in Australian serum than in Swedish plasma.

Persistent organochlorine pesticides in human milk samples from Australia.

Human milk has been used as a surrogate for the assessment of body burden and exposure to persistent lipophilic organochlorine pesticides (OCPs). With the exception of restricted use of mirex, the use of persistent, lipophilic OCPs has been banned in Australia since the 1980s. The decline of human body burden of OCPs following their ban in many industrialised countries is well recorded worldwide from the 1970s until the 1990s though little is known on whether these trends are continuing. In this study, 157 human milk samples collected during 2002 and 2003 as well as 24 samples collected in 1993 were analysed as 20 regional pools for 17 OCPs. OCPs were detected in all pooled human milk samples from 2002/03 typically with highest concentrations of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) (mean+/-standard deviation; median concentration 311+/-174; 279 ng g(-1) lipid) followed by beta-hexachlorocyclohexane (beta-HCH) (80+/-173; 21 ng g(-1) lipid). Other OCPs consistently detected included dieldrin (16+/-6; 17 ng g(-1) lipid), hexachlorobenzene (HCB) (18+/-16; 14 ng g(-1) lipid), transnonachlor (11+/-5; 9 ng g(-1) lipid) and p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) (9+/-6; 7 ng g(-1) lipid). The results from this study indicated that following a substantial decline of OCP concentrations from the early 1980s to the 1990s, little decline could be observed since then. Furthermore the use of multivariate statistics indicated some regional trends with slightly higher levels of the broadly used insecticides DDT and HCH in both historic and recent samples from Melbourne, whereas, sample pools collected from mothers that lived in rural Queensland and New South Wales as well as Adelaide and Sydney showed comparatively higher levels of heptachlor and dieldrin - both of which have been used for termite treatment. These results indicate that even 20 years after the discontinuation of usage, historical use of OCPs rather than exposure via global transport of OCPs is responsible for continuous low exposure in Australia.

Paediatric appendiceal ultrasound: a survey of Australasian sonographers' opinions on examination performance and sonographic criteria.

INTRODUCTION: The objectives of this study were to identify knowledge gaps and/or perceived limitations in the performance of paediatric appendiceal ultrasound by Australasian sonographers. We hypothesised that: sonographers' confidence in visualising the appendix in children was poor, particularly outside predominantly paediatric practice; workplace support for prolonging examinations to improve visualisation was limited; and the sonographic criteria applied in diagnosis did not reflect contemporary literature. METHODS: A cross-sectional survey of Australasian sonographers regarding paediatric appendicitis was conducted using a mixed methods approach (quantitative and qualitative data). Text responses were analysed for key themes, and quantitative data analysed using chi-square, Mann-Whitney U and Wilcoxon signed-rank tests. RESULTS: Of the 124 respondents, 27 (21.8%) reported a visualisation rate of less than 10%. Workplace support for extending examination time was significantly related to a higher appendix visualisation rate (χ2 (2) = 16.839, P < 0.001). Text responses reported frustration locating the appendix and a desire for more time and practice to improve visualisation. Sonographers suggested a significantly lower maximum diameter cut-off in a 5-year-old compared to a 13-year-old (Z = -6.07, P < 0.001), and considered the presence of inflamed peri-appendiceal mesentery as the most useful sonographic criterion in diagnosing acute appendicitis. CONCLUSIONS: Respondents had a low opinion of their ability to confidently identify the appendix. Confidence was greater in those centres where extending scanning time was encouraged. Application of echogenic mesentery as the most significant secondary sonographic criterion is supported by recent studies. Opinions of diameter cut-offs varied, indicating potential for improved awareness of recent research.

An image-guided radiotherapy decision support framework incorporating a Bayesian network and visualization tool.

PURPOSE: To describe a Bayesian network (BN) and complementary visualization tool that aim to support decision-making during online cone-beam computed tomography (CBCT)-based image-guided radiotherapy (IGRT) for prostate cancer patients. METHODS: The BN was created to represent relationships between observed prostate, proximal seminal vesicle (PSV), bladder and rectum volume variations, an image feature alignment score (FASTV_OAR ), delivered dose, and treatment plan compliance (TPC). Variables influencing tumor volume (TV) targeting accuracy such as intrafraction motion, and contouring and couch shift errors were also represented. A score of overall TPC (FASglobal ) and factors such as image quality were used to inform the BN output node providing advice about proceeding with treatment. The BN was quantified using conditional probabilities generated from published studies, FASTV_OAR/global modeling, and a survey of IGRT decision-making practices. A new IGRT visualization tool (IGRTREV ), in the form of Mollweide projection plots, was developed to provide a global summary of residual errors after online CBCT-planning CT registration. Sensitivity and scenario analyses were undertaken to evaluate the performance of the BN and the relative influence of the network variables on TPC and the decision to proceed with treatment. The IGRTREV plots were evaluated in conjunction with the BN scenario testing, using additional test data generated from retrospective CBCT-planning CT soft-tissue registrations for 13/36 patients whose data were used in the FASTV_OAR/global modeling. RESULTS: Modeling of the TV targeting errors resulted in a very low probability of corrected distances between the CBCT and planning CT prostate or PSV volumes being within their thresholds. Strength of influence evaluation with and without the BN TV targeting error nodes indicated that rectum- and bladder-related network variables had the highest relative importance. When the TV targeting error nodes were excluded from the BN, TPC was sensitive to observed PSV and rectum variations while the decision to treat was sensitive to observed prostate and PSV variations. When root nodes were set so the PSV and rectum variations exceeded thresholds, the probability of low TPC increased to 40%. Prostate and PSV variations exceeding thresholds increased the likelihood of repositioning or repeating patient preparation to 43%. Scenario testing using the test data from 13 patients, demonstrated two cases where the BN provided increased high TPC probabilities, despite some of the prostate and PSV volume variation metrics not being within tolerance. The IGRTREV tool was effective in highlighting and quantifying where TV and OAR variations occurred, supporting the BN recommendation to reposition the patient or repeat their bladder and bowel preparation. In another case, the IGRTREV tool was also effective in highlighting where PSV volume variation significantly exceeded tolerance when the BN had indicated to proceed with treatment. CONCLUSIONS: This study has demonstrated that both the BN and IGRTREV plots are effective tools for inclusion in a decision support system for online CBCT-based IGRT for prostate cancer patients. Alternate approaches to modeling TV targeting errors need to be explored as well as extension of the BN to support offline IGRT decisions related to adaptive radiotherapy.

A feature alignment score for online cone-beam CT-based image-guided radiotherapy for prostate cancer.

PURPOSE: To develop a method for scoring online cone-beam CT (CBCT)-to-planning CT image feature alignment to inform prostate image-guided radiotherapy (IGRT) decision-making. The feasibility of incorporating volume variation metric thresholds predictive of delivering planned dose into weighted functions, was investigated. METHODS: Radiation therapists and radiation oncologists participated in workshops where they reviewed prostate CBCT-IGRT case examples and completed a paper-based survey of image feature matching practices. For 36 prostate cancer patients, one daily CBCT was retrospectively contoured then registered with their plan to simulate delivered dose if (a) no online setup corrections and (b) online image alignment and setup corrections, were performed. Survey results were used to select variables for inclusion in classification and regression tree (CART) and boosted regression trees (BRT) modeling of volume variation metric thresholds predictive of delivering planned dose to the prostate, proximal seminal vesicles (PSV), bladder, and rectum. Weighted functions incorporating the CART and BRT results were used to calculate a score of individual tumor and organ at risk image feature alignment (FASTV_OAR ). Scaled and weighted FASTV_OAR were then used to calculate a score of overall treatment compliance (FASglobal ) for a given CBCT-planning CT registration. The FASTV_OAR were assessed for sensitivity, specificity, and predictive power. FASglobal thresholds indicative of high, medium, or low overall treatment plan compliance were determined using coefficients from multiple linear regression analysis. RESULTS: Thirty-two participants completed the prostate CBCT-IGRT survey. While responses demonstrated consensus of practice for preferential ranking of planning CT and CBCT match features in the presence of deformation and rotation, variation existed in the specified thresholds for observed volume differences requiring patient repositioning or repeat bladder and bowel preparation. The CART and BRT modeling indicated that for a given registration, a Dice similarity coefficient >0.80 and >0.60 for the prostate and PSV, respectively, and a maximum Hausdorff distance <8.0 mm for both structures were predictive of delivered dose ± 5% of planned dose. A normalized volume difference <1.0 and a CBCT anterior rectum wall >1.0 mm anterior to the planning CT anterior rectum wall were predictive of delivered dose >5% of planned rectum dose. A normalized volume difference <0.88, and a CBCT bladder wall >13.5 mm inferior and >5.0 mm posterior to the planning CT bladder were predictive of delivered dose >5% of planned bladder dose. A FASTV_OAR >0 is indicative of delivery of planned dose. For calculated FASTV_OAR for the prostate, PSV, bladder, and rectum using test data, sensitivity was 0.56, 0.75, 0.89, and 1.00, respectively; specificity 0.90, 0.94, 0.59, and 1.00, respectively; positive predictive power 0.90, 0.86, 0.53, and 1.00, respectively; and negative predictive power 0.56, 0.89, 0.91, and 1.00, respectively. Thresholds for the calculated FASglobal of were low <60, medium 60-80, and high >80, with a 27% misclassification rate for the test data. CONCLUSIONS: A FASglobal incorporating nested FASTV_OAR and volume variation metric thresholds predictive of treatment plan compliance was developed, offering an alternative to pretreatment dose calculations to assess treatment delivery accuracy.

Temporal trends in serum polybrominated diphenyl ether concentrations in the Australian population, 2002-2013.

In Australia, systematic biomonitoring of persistent organic pollutants (POPs) in pooled serum samples stratified by age and sex has occurred every two years between 2002/03 and 2012/13. Multiple regression modeling on log10-transformed serum pool concentrations of BDEs 47, 99, 100 and 153 and on the sum of these (Σ4PBDE) was conducted to examine trends by sex and time since baseline, stratified by age group. Temporal trends were age- and congener-specific, with the largest changes per year of observation in the 0-4 year old group, with ß (SE) = -0.098 (0.013) for log10BDE47; -0.119 (0.012) for log10BDE99; -0.084 (0.014) for log10BDE100, and -0.053 (0.013) for log10BDE153, all p < 0.001. Adults over age 16 showed much smaller decreasing temporal trends for BDE47 and BDE99, no significant changes in BDE100, and, for the oldest age groups, slight increases in BDE153. As a result, Σ4PBDE concentrations were stable over the entire time period in adults older than 16. Concentrations of each BDE in pools from females aged 31-60 were significantly lower compared to males. Relative proportions of BDE47 declined, while BDE153 accounted for a greater share of Σ4PBDE over time. Whereas previously we saw a large elevation in the youngest age groups compared to older children and adults, this is no longer the case. This may be due to a decline in infant and toddler exposures in the indoor environment as use of PBDEs in consumer products has been phased out, suggesting temporal changes in the relative sources of exposure for young children in Australia.

Urinary metabolites of organophosphate esters: Concentrations and age trends in Australian children.

There is growing concern around the use of organophosphate esters (OPEs) due to their suspected reproductive toxicity, carcinogenicity, and neurotoxicity. OPEs are used as flame retardants and plasticizers, and due to their extensive application in consumer products, are found globally in the indoor environment. Early life exposure to OPEs is an important risk factor for children's health, but poorly understood. To study age and sex trends of OPE exposures in infants and young children, we collected, pooled, and analysed urine samples from children aged 0-5years from Queensland, Australia for 9 parent OPEs and 11 metabolites. Individual urine samples (n=400) were stratified by age and sex, and combined into 20 pools. Three individual breast milk samples were also analysed to provide a preliminary estimate on the contribution of breast milk to the intake of OPEs. Bis(1-chloroisopropyl) phosphate (BCIPP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP), bis(1,3-dichloroisopropyl) phosphate (BDCIPP), dibutyl phosphate (DBP), diphenyl phosphate (DPHP), bis(2-butoxyethyl) phosphate (BBOEP), bis(2-butoxyethyl) 3-hydroxyl-2-butoxyethyl phosphate (3OH-TBOEP), and bis(2-butoxyethyl) hydroxyethyl phosphate (BBOEHEP) were detected in all urine samples, followed by bis(methylphenyl) phosphate (80%), and bis(2-ethylhexyl) phosphate (BEHP, 20%), and bis(2-chloroethyl) phosphate (BCEP, 15%). Concentrations of tris(2-chloroethyl) phosphate (TCEP), BCEP, tris(2-ethylhexyl) phosphate (TEHP), and DBP decreased with age, while bis(methylphenyl) phosphate (BMPP) increased with age. Significantly higher concentrations of DPHP (p=0.039), and significantly lower concentrations of TEHP (p=0.006) were found in female samples compared to males. The estimated daily intakes (EDIs) via breastfeeding, were 4.6, 26 and 76ng/kg/day for TCEP, TBP and TEHP, respectively, and were higher than that via air and dust, suggesting higher exposure through consumption of breast milk.

Polybrominated diphenyl ethers (PBDEs) in human milk from Australia.

Polybrominated diphenyl ethers (PBDEs) are flame retardants added to a multitude of products to reduce flammability. PBDEs have been widely detected and quantified in biota and humans in many industrialised countries from the Northern Hemisphere. However data concerning the levels of these compounds in the Australian population and environment remain limited. The objectives of this study were to determine PBDE concentrations and congener profiles in Australian human milk and compare this to concentrations found in other countries. Pooled human milk samples obtained from mothers residing in 12 regions of Australia were analysed by HRGC/HRMS for 18 PBDE congeners. In total, 157 human milk samples collected in 2002 and 2003 were divided into 17 regional pools. PBDEs were detected in all pools of human milk from Australia. The mean+/-standard deviation and median summation operatorPBDE concentrations were 11.1+/-3.2 and 11.0 ng g(-1) lipid, respectively with a range of 6.1-18.7 ng g(-1) lipid. The congener profile was dominated by BDE-47 followed by BDE-99, -100, -153, -154 and -183. Regional differences were evaluated, but no trends were observed. The data suggest regional differences are likely to be small if they exist at all. The concentrations of PBDEs found in Australian human milk were lower than those reported from North America but higher than those reported from Europe and Asia. Our results suggest that the exposure pathways which contribute to the PBDE body burden in the Australian population require a better understanding in order to determine future policy regarding their use and disposal.

Risk Profiles for Sensorineural Hearing Loss in Patients with Head and Neck Cancer Receiving Cisplatin-based Chemoradiation.

OBJECTIVE: Sensorineural hearing loss (SNHL) is a significant toxicity experienced by some patients undergoing cisplatin-based chemoradiation therapy for head and neck cancer. Therefore, SNHL risk profiles were created based on demographics, hearing thresholds, and treatment parameters. METHODS: Thirty-eight patients with squamous cell carcinoma of the head and neck, treated with postoperative or definitive cisplatin-based chemoradiation at the Princess Alexandra Hospital between 2010 and 2013, were retrospectively reviewed. Patients with pretreatment otologic problems were excluded. Regression models analysed the contributions of collected variables. RESULTS: All patients (100%) received multiple audiological assessments, with 21 (55.3%) receiving baseline assessment. The mean hearing deterioration at pure-tone average 1-2-4 kHz was mild (range 22.4-27.6 dB). However, clinically significant SNHL was evident in 37 (97.3%), 24 (63.2%), and 14 (36.8%) patients at 8 kHz and pure-tone averages 0.5-1-2 kHz and 1-2-4 kHz, respectively. Principal component analysis indicated two profiles: (1) low or medium frequency SNHL and (2) high-frequency SNHL. Multivariate analysis demonstrated tobacco consumption (ρ < 0.006) and alcohol intake (ρ < 0.08) predicted high-frequency SNHL (F(3,33) = 3.59, ρ < 0.02, R2 = 0.177), with cumulative cisplatin dose (ρ < 0.006) predicting low and medium frequency SNHL (F(3,34) = 14.81, ρ < 0.001, R2 = 0.528). CONCLUSIONS: Although hearing loss rates may be under reported without routine audiological assessment, the incidence of cisplatin-based chemoradiation-induced SNHL, in this study, is high. The proposed predictive model can be used as a prognostic tool and potentially mitigate adverse outcomes.

Utility of Bayesian networks in QMRA-based evaluation of risk reduction options for recycled water.

BACKGROUND: Quantitative microbial risk assessment (QMRA), the current method of choice for evaluating human health risks associated with disease-causing microorganisms, is often constrained by issues such as availability of required data, and inability to incorporate the multitude of factors influencing risk. Bayesian networks (BNs), with their ability to handle data paucity, combine quantitative and qualitative information including expert opinions, and ability to offer a systems approach to characterisation of complexity, are increasingly recognised as a powerful, flexible tool that overcomes these limitations. OBJECTIVES: We present a QMRA expressed as a Bayesian network (BN) in a wastewater reuse context, with the objective of demonstrating the utility of the BN method in health risk assessments, particularly for evaluating a range of exposure and risk mitigation scenarios. As a case study, we examine the risk of norovirus infection associated with wastewater-irrigated lettuce. METHODS: A Bayesian network was developed following a QMRA approach, using published data, and reviewed by domain experts using a participatory process. DISCUSSION: Employment of a BN facilitated rapid scenario evaluations, risk minimisation, and predictive comparisons. The BN supported exploration of conditions required for optimal outcomes, as well as investigation of the effect on the reporting nodes of changes in 'upstream' conditions. A significant finding was the indication that if maximum post-treatment risk mitigation measures were implemented, there was a high probability (0.84) of a low risk of infection regardless of fluctuations in other variables, including norovirus concentration in treated wastewater. CONCLUSION: BNs are useful in situations where insufficient empirical data exist to satisfy QMRA requirements and they are exceptionally suited to the integration of risk assessment and risk management in the QMRA context. They allow a comprehensive visual appraisal of major influences in exposure pathways, and rapid interactive risk assessment in multifaceted water reuse scenarios.