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In light of a modern understanding of early Eocene greenhouse climate fluctuations and new highly seasonal fluvial system faces models, the role of climate in the evolution of one classically-cited continental, terminal lake system is re-examined. Detailed stratigraphic description and elemental abundance data from fifteen cores and seven outcrop regions of the Green River Formation were used to construct a ~150 km cross section across the Uinta Basin, Utah, USA. Lake Uinta in the Uinta Basin is divided into five lake phases: (1) post-Paleocene Eocene Thermal Maximum, (2) peak Eocene hyperthermal, (3) waning hyperthermal, Early Eocene Climatic Optimum (EECO), (4) posthyperthermal, and (5) post-EECO regimes, based primarily on climatically driven changes in fluvial style in combination with sedimentary indicators of lacustrine carbonate deposition, organic matter preservation, salinity, and lake depth. Basinwide siliciclastic dominated intervals were deposited by highly seasonal fluvial systems and record negative organic carbon isotope excursions associated with early Eocene abrupt, transient global warming (hyperthermal) events. Carbonate dominated or organic rich intervals record stable, less seasonal climate periods between hyperthermals, with lower siliciclastic sediment supply allowing the development of carbonate and organic matter preservation. The stratigraphic progression from alternating organic rich and lean zones to the overlying organic rich Mahogany and R8 zones represents the global transition out of the pulsed early Eocene hyperthermal climate regime to a time of sediment starvation and lake stratification, sequestering sedimentary organic carbon. This study provides a novel approach to terrestrial paleoclimate reconstruction that relies largely on unique sedimentary indicators and secondarily on isotopic proxy records within the context of a large basin-wide sedimentologic and stratigraphic data set, thus setting the stage for future detailed geochemical terrestrial paleoclimate proxy development. [ABSTRACT FROM AUTHOR]

At the turn of the century a fundamental resolution barrier in fluorescence microscopy known as the diffraction limit was broken, giving rise to the field of super-resolution microscopy. Subsequent nanoscopic investigation with visible light revolutionised our understanding of how previously unknown molecular features give rise to the emergent behaviour of cells. It transpires that the devil is in these fine molecular details, and essential nanoscale processes were found everywhere researchers chose to look. Now, after nearly two decades, super-resolution microscopy has begun to address previously unmet challenges in the study of human disease and is poised to become a pivotal tool in drug discovery., Competing Interests: Declaration of interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Philip Auckland reports a relationship with Medicines Discovery Catapult that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Background: Per- and polyfluoroalkyl substances (PFASs) are persistent manmade compounds used in aqueous film forming foam (AFFF). The extensive use of AFFF has led to widespread environmental PFAS contamination and exposures of firefighters., Objectives: To determine PFAS blood serum concentration trends and apparent serum half-lives in firefighters after the replacement of AFFF., Methods: Current and former employees of an Australian corporation providing firefighting services, where AFFF formulations had been used since the 1980s up until 2010, were recruited in 2018-2019 to participate in this study. Special focus was put on re-recruiting participants who had provided blood samples five years prior (2013-2014). Participants were asked to provide a blood sample and fill in a questionnaire. Serum samples were analysed for 40 different PFASs using HP LC-MS/MS., Results: A total of 799 participants provided blood samples in 2018-2019. Of these, 130 previously provided blood serum in 2013-2014. In 2018-2019, mean (arithmetic) serum concentrations of perfluorooctane sulfonate (PFOS, 27 ng/mL), perfluoroheptane sulfonate (PFHpS, 1.7 ng/mL) and perfluorohexane sulfonate (PFHxS, 14 ng/mL) were higher than the levels in the general Australian population. Serum concentrations were associated with the use of PFOS/PFHxS based AFFF. Participants who commenced service after the replacement of this foam had serum concentrations similar to those in the general population. Mean (arithmetic) individual apparent half-lives were estimated to be 5.0 years (perfluorooctanoic acid (PFOA)), 7.8 years (PFHxS), 7.4 years (PFHpS) and 6.5 years (PFOS)., Conclusion: This study shows how workplace interventions such as replacement of AFFF can benefit employees at risk of occupational exposure., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear., Methods: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point., Results: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group., Conclusions: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.)., (Copyright © 2021 Massachusetts Medical Society.)

Health concerns and related regulation of bisphenol A (BPA) in some countries have led to an increase in the production and use of unregulated and poorly understood BPA analogues, including bisphenol S (BPS), bisphenol F (BPF), bisphenol B (BPB), and bisphenol AF (BPAF). To assess the temporal trends of human exposure to BPA analogues, urine and wastewater samples were collected from South East Queensland, Australia between 2012 and 2017 and analyzed for five bisphenols using validated isotope dilution liquid chromatography tandem mass spectrometry methods. BPA and BPS were the predominant bisphenols detected in both urine and wastewater samples, with median concentrations of 2.5 and 0.64 μg/L in urine and 0.94 and 1.1 μg/L in wastewater, respectively. BPB, BPF, and BPAF had low detection frequencies in both urine and wastewater samples. Concentrations of BPA in both urine and wastewater decreased over the sampling period, whereas concentrations of BPS increased, suggesting that BPS has become a BPA replacement. The contributions of urinary excretion to wastewater were calculated by the ratio of daily per capita urinary excretion to wastewater-based mass loads of bisphenols. Urinary BPA and BPS contributed to less than 1% of the load found in wastewater, indicating that much of the BPA and BPS originates from other sources.

Background: Increased public awareness of PFAS contamination in Australia has resulted in serum biomonitoring efforts in individuals in potentially affected communities. However, population-based reference values for assessing whether individual results exceed the typical range in the Australian general population are not currently available., Objective: Estimate population upper bound reference values based on updated serum PFAS concentrations in pooled samples from southeast Queensland, Australia and population variation observed in the US National Health and Nutrition Examination Survey (NHANES) datasets., Methods: We calculated ratios of 95th percentile to arithmetic mean (P95:AM ratios) using data from the NHANES 2013-14 and 2015-16 cycle samples for frequently detected PFASs: PFOA, linear and branched PFOS, perfluorononanoate (PFNA), perfluorodecanoate (PFDA), and perfluorohexanesulfonate (PFHxS). We estimated Australian age-specific means for PFAS using pooled serum samples collected in 2014-15 and 2016-17. We used the P95:AM ratios to estimate 95th percentile concentrations in the Australian population based on the results of the 2016-17 pooled samples., Results and Conclusions: P95:AM ratios for each PFAS were similar across NHANES cycle and age group, so overall compound-specific ratios were estimated for PFOA (2.1), PFNA (2.4), PFDA (2.7), PFHxS (2.7), and linear (2.4) and summed PFOS (2.3). Australian mean PFAS concentrations continued previously reported declining trends. The estimated P95 values can be used as preliminary substitutes for more rigorous population reference values to identify samples with clearly elevated serum PFAS concentrations in Australian biomonitoring efforts. Given uncertainties and variability inherent in this evaluation, the estimated P95 values should be interpreted with caution. Mean and estimated P95 serum PFAS concentrations in Australia should continue to be monitored to document declining trends in population serum concentrations., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

The cytokine interleukin-1 (IL-1) is a key contributor to neuroinflammation and brain injury, yet mechanisms by which IL-1 triggers neuronal injury remain unknown. Here we induced conditional deletion of IL-1R1 in brain endothelial cells, neurons and blood cells to assess site-specific IL-1 actions in a model of cerebral ischaemia in mice. Tamoxifen treatment of IL-1R1 floxed ( fl/fl ) mice crossed with mice expressing tamoxifen-inducible Cre-recombinase under the Slco1c1 promoter resulted in brain endothelium-specific deletion of IL-1R1 and a significant decrease in infarct size (29%), blood-brain barrier (BBB) breakdown (53%) and neurological deficit (40%) compared to vehicle-treated or control (IL-1R1 fl/fl ) mice. Absence of brain endothelial IL-1 signalling improved cerebral blood flow, followed by reduced neutrophil infiltration and vascular activation 24 h after brain injury. Conditional IL-1R1 deletion in neurons using tamoxifen inducible nestin-Cre mice resulted in reduced neuronal injury (25%) and altered microglia-neuron interactions, without affecting cerebral perfusion or vascular activation. Deletion of IL-1R1 specifically in cholinergic neurons reduced infarct size, brain oedema and improved functional outcome. Ubiquitous deletion of IL-1R1 had no effect on brain injury, suggesting beneficial compensatory mechanisms on other cells against the detrimental effects of IL-1 on endothelial cells and neurons. We also show that IL-1R1 signalling deletion in platelets or myeloid cells does not contribute to brain injury after experimental stroke. Thus, brain endothelial and neuronal (cholinergic) IL-1R1 mediate detrimental actions of IL-1 in the brain in ischaemic stroke. Cell-specific targeting of IL-1R1 in the brain could therefore have therapeutic benefits in stroke and other cerebrovascular diseases., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

A range of pesticides are available in Australia for use in agricultural and domestic settings to control pests, including organophosphate and pyrethroid insecticides, herbicides, and insect repellents, such as N,N-diethyl-meta-toluamide (DEET). The aim of this study was to provide a cost-effective preliminary assessment of background exposure to a range of pesticides among a convenience sample of Australian residents. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n = 24 pools of 100 specimens). Concentrations of urinary pesticide biomarkers were quantified using solid-phase extraction coupled with isotope dilution high-performance liquid chromatography-tandem mass spectrometry. Geometric mean biomarker concentrations ranged from <0.1 to 36.8 ng/mL for organophosphate insecticides, <0.1 to 5.5 ng/mL for pyrethroid insecticides, and <0.1 to 8.51 ng/mL for all other biomarkers with the exception of the DEET metabolite 3-diethylcarbamoyl benzoic acid (4.23 to 850 ng/mL). We observed no association between age and concentration for most biomarkers measured but noted a "U-shaped" trend for five organophosphate metabolites, with the highest concentrations observed in the youngest and oldest age strata, perhaps related to age-specific differences in behavior or physiology. The fact that concentrations of specific and non-specific metabolites of the organophosphate insecticide chlorpyrifos were higher than reported in USA and Canada may relate to differences in registered applications among countries. Additional biomonitoring programs of the general population and focusing on vulnerable populations would improve the exposure assessment and the monitoring of temporal exposure trends as usage patterns of pesticide products in Australia change over time.

Dialkyl phthalate esters (phthalates) are ubiquitous chemicals used extensively as plasticizers, solvents and adhesives in a range of industrial and consumer products. 1,2-Cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is a phthalate alternative introduced due to a more favourable toxicological profile, but exposure is largely uncharacterised. The aim of this study was to provide the first assessment of exposure to phthalates and DINCH in the general Australian population. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n=24 pools of 100). Concentrations of free and total species were measured using online solid phase extraction isotope dilution high performance liquid chromatography tandem mass spectrometry. Concentrations ranged from 2.4 to 71.9ng/mL for metabolites of di(2-ethylhexyl)phthalate, and from <0.5 to 775ng/mL for all other metabolites. Our data suggest that phthalate metabolites concentrations in Australia were at least two times higher than in the United States and Germany; and may be related to legislative differences among countries. DINCH metabolite concentrations were comparatively low and consistent with the limited data available. Ongoing biomonitoring among the general Australian population may help assess temporal trends in exposure and assess the effectiveness of actions aimed at reducing exposures., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Parabens, benzophenone-3 and triclosan are common ingredients used as preservatives, ultraviolet radiation filters and antimicrobial agents, respectively. Human exposure occurs through consumption of processed food and use of cosmetics and consumer products. The aim of this study was to provide a preliminary characterisation of exposure to selected personal care product chemicals in the general Australian population. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n=24 pools of 100). Concentrations of free and total (sum of free plus conjugated) species of methyl, ethyl, propyl and butyl paraben, benzophenone-3 and triclosan were quantified using isotope dilution tandem mass spectrometry; with geometric means 232, 33.5, 60.6, 4.32, 61.5 and 87.7ng/mL, respectively. Age was inversely associated with paraben concentration, and females had concentrations approximately two times higher than males. Total paraben and benzophenone-3 concentrations are significantly higher than reported worldwide, and the average triclosan concentration was more than one order of magnitude higher than in many other populations. This study provides the first data on exposure of the general Australian population to a range of common personal care product chemical ingredients, which appears to be prevalent and warrants further investigation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Used frequently in food contact materials, bisphenol A (BPA) has been studied extensively in recent years, and ubiquitous exposure in the general population has been demonstrated worldwide. Characterizing within- and between-individual variability of BPA concentrations is important for characterizing exposure in biomonitoring studies, and this has been investigated previously in adults, but not in children. The aim of this study was to characterize the short-term variability of BPA in spot urine samples in young children. Children aged ≥2-<4 years (n=25) were recruited from an existing cohort in Queensland, Australia, and donated four spot urine samples each over a two day period. Samples were analysed for total BPA using isotope dilution online solid phase extraction-liquid chromatography-tandem mass spectrometry, and concentrations ranged from 0.53 to 74.5 ng/ml, with geometric mean and standard deviation of 2.70 ng/ml and 2.94 ng/ml, respectively. Sex and time of sample collection were not significant predictors of BPA concentration. The between-individual variability was approximately equal to the within-individual variability (ICC=0.51), and this ICC is somewhat higher than previously reported literature values. This may be the result of physiological or behavioural differences between children and adults or of the relatively short exposure window assessed. Using a bootstrapping methodology, a single sample resulted in correct tertile classification approximately 70% of the time. This study suggests that single spot samples obtained from young children provide a reliable characterization of absolute and relative exposure over the short time window studied, but this may not hold true over longer timeframes., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA) is used extensively in food-contact materials and has been detected routinely in populations worldwide; this exposure has been linked to a range of negative health outcomes in humans. There is some evidence of an association between BPA and different socioeconomic variables which may be the result of different dietary patterns. The aim of this study was to conduct a preliminary investigation of the association between BPA and socioeconomic status in Australian children using pooled urine specimens and an area-level socioeconomic index. Surplus pathology urine specimens collected from children aged 0-15 years in Queensland, Australia, as samples of convenience (n=469), were pooled by age, sex and area-level socioeconomic index (n=67 pools) and analysed for total BPA using online solid-phase extraction LC-MS/MS. Concentration ranged from 1.08 to 27.4 ng/ml with geometric mean 2.57 ng/ml, and geometric mean exposure was estimated as 70.3 ng/kg d(-1). Neither BPA concentration nor excretion was associated with age or sex, and the authors found no evidence of an association with socioeconomic status. These results suggest that BPA exposure is not associated with socioeconomic status in the Australian population due to relatively homogenous exposures in Australia, or that the socioeconomic gradient is relatively slight in Australia compared with other OECD countries.

Objective: To determine the stability and reproducibility of the sodium magnetic resonance imaging (MRI) signal measured in the articular cartilage of the knee in both healthy volunteers and osteoarthritis (OA) patients., Design: This was a prospective Research Ethics Committee approved study that acquired sodium and proton MRI data from 15 subjects with OA (three males, age 64 ± 10) and five healthy controls age and sex matched over the group. Each subject underwent standing planar radiographs of their knees for radiological scoring as well as symptomatological assessment questionnaires. In two MRI sessions on the same day, high resolution double-echo steady state (DESS) and 3D short echo time sodium MRI images of the most diseased knee were acquired and co-registered in each session. A blinded reader (LT) manually delineated the articular cartilage into four discrete regions, and two combined regions, on the DESS images. These regions were applied to the sodium images, and a median sodium signal from each reported. Within-subject and between-subject coefficients of variation were estimated and intraclass correlation coefficients for the healthy control group, OA subject group, and all pooled subjects group were calculated., Results: Within-subject variability of sodium MRI at 3T was 3.2% overall, and 2.0% in healthy age-matched volunteers compared to a reproducibility of 3.6% on OA subjects., Conclusions: The reproducibility of sodium MRI was similar in both healthy controls and OA subjects. Researchers piloting techniques in healthy controls thus may expect a similar reproducibility in a controlled trial involving subjects with American College of Rheumatology (ACR)-defined OA of the knee., (Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: This is an updated version of the Cochrane review published in Issue 4, 1998. Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability, using lower doses of each drug to achieve the same degree of pain relief. Previously we concluded that addition of codeine to paracetamol provided additional pain relief, but at expense of additional adverse events. New studies have been published since. This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data, and compare findings with other analgesics evaluated similarly., Objectives: Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain, increase in efficacy due to the codeine component, and associated adverse events., Search Strategy: We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update., Selection Criteria: Randomised, double-blind, placebo-controlled trials of paracetamol plus codeine, compared with placebo or the same dose of paracetamol alone, for relief of acute postoperative pain in adults., Data Collection and Analysis: Two authors assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). Proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected., Main Results: Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800 to 1000 mg paracetamol plus 60 mg codeine, 3.9 (2.9 to 4.5) for 600 to 650 mg paracetamol plus 60 mg codeine, and 6.9 (4.8 to 12) for 300 mg paracetamol plus 30 mg codeine. Time to use of rescue medication was over four hours with paracetamol plus codeine and two hours with placebo. The NNT to prevent remedication was 5.6 (4.0 to 9.0) for 600 mg paracetamol plus 60 mg codeine over four to six hours. Adverse events increased of mainly mild to moderate severity with paracetamol plus codeine than placebo.Fourteen studies, with 926 participants, were included in the comparison of paracetamol plus codeine with the same dose of paracetamol alone. Addition of codeine increased proportion of participants achieving at least 50% pain relief over four-to-six hours by 10 to 15%, increased time to use of rescue medication by about one hour, and reduced proportion of participants needing rescue medication by about 15% (NNT to prevent remedication 6.9 (4.2 to 19). Adverse events were mainly mild to moderate in severity and incidence did not differ between groups., Authors' Conclusions: This update confirms previous findings that combining paracetamol with codeine provided clinically useful levels of pain relief in about 50% of patients with moderate to severe postoperative pain, compared with under 20% with placebo. New information for remedication shows that the combination extended the duration of analgesia by about one hour compared to treatment with the same dose of paracetamol alone. At higher doses, more participants experienced adequate pain relief, but the amount of information available for the 1000 mg paracetamol plus 60 mg codeine dose was small, and based on limited information.

Background: This is an updated version of the original Cochrane review published in Issue 1, 2004 - this original review had been split from a previous title on 'Single dose paracetamol (acetaminophen) with and without codeine for postoperative pain'. The last version of this review concluded that paracetamol is an effective analgesic for postoperative pain, but additional trials have since been published. This review sought to evaluate the efficacy and safety of paracetamol using current data, and to compare the findings with other analgesics evaluated in the same way., Objectives: To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain., Search Strategy: We searched The Cochrane Library, MEDLINE, EMBASE, the Oxford Pain Relief Database and reference lists of articles to update an existing version of the review in July 2008., Selection Criteria: Randomised, double-blind, placebo-controlled clinical trials of paracetamol for acute postoperative pain in adults., Data Collection and Analysis: Two review authors independently assessed trial quality and extracted data. Area under the "pain relief versus time" curve was used to derive the proportion of participants with paracetamol or placebo experiencing at least 50% pain relief over four to six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated, with 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use, were sought as measures of duration of analgesia. Information on adverse events and withdrawals was also collected., Main Results: Fifty-one studies, with 5762 participants, were included: 3277 participants were treated with a single oral dose of paracetamol and 2425 with placebo. About half of participants treated with paracetamol at standard doses achieved at least 50% pain relief over four to six hours, compared with about 20% treated with placebo. NNTs for at least 50% pain relief over four to six hours following a single dose of paracetamol were as follows: 500 mg NNT 3.5 (2.7 to 4.8); 600 to 650 mg NNT 4.6 (3.9 to 5.5); 975 to 1000 mg NNT 3.6 (3.4 to 4.0). There was no dose response. Sensitivity analysis showed no significant effect of trial size or quality on this outcome.About half of participants needed additional analgesia over four to six hours, compared with about 70% with placebo. Five people would need to be treated with 1000 mg paracetamol, the most commonly used dose, to prevent one needing rescue medication over four to six hours, who would have needed it with placebo. Adverse event reporting was inconsistent and often incomplete. Reported adverse events were mainly mild and transient, and occurred at similar rates with 1000 mg paracetamol and placebo. No serious adverse events were reported. Withdrawals due to adverse events were uncommon and occurred in both paracetamol and placebo treatment arms., Authors' Conclusions: A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

The results of this study provide a measure of the levels of dioxin-like compounds (polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls) in pooled blood serum collected throughout Australia in 2003. De-identified samples selected from surplus pathology samples were stratified on the basis of gender, region and age. In total 9090 samples were collected and analysed as 96 pools. Dioxin-like chemicals were detected in all strata. The mean and median levels expressed as TEQ values for all pooled samples were 10.9+/-1.0 pg TEQ g(-1) lipid and 8.3 pg TEQ g(-1) lipid. For males and females the mean levels were 10.4+/-0.6 pg TEQ g(-1) lipid and 11.5+/-1.5 pg TEQ g(-1) lipid, respectively. A direct relationship of increasing dioxin-like chemical levels with increasing age was observed and could be described by the following equation: Levels in blood expressed as pg TEQ g(-1) lipid = 3.3 exp(0.0251 age) (r2 = 0.87). No significant differences were observed in the levels of dioxin-like chemicals in samples collected from males and females. In addition, the levels of dioxin-like chemicals across the five regions were similar within each age range. In summary, the levels of dioxin-like chemicals in the Australian population are low compared to international levels and are similar across all regions of Australia within each designated age range. The levels of these chemicals increase with age and can be estimated if the age of an individual is known.

Design: Human milk samples were collected and analysed for the levels of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and selected dioxin-like polychlorinated biphenyls (PCBs). In total, 157 individual samples collected during 2002 and 2003 as well as 24 samples collected in 1993 were analysed as 20 pools., Results: PCDDs, PCDFs and dioxin-like PCBs were detected in all pooled samples. For samples collected during 2002/2003, the TEQ(DFP) ranged from 6.0 to 15.2 pg TEQ g(-1) lipid with an average of 9.0 pg TEQ g(-1) lipid. The average lipid content was 3.7+/-0.5%. No systematic differences were observed in the levels of PCDDs, PCDFs and PCBs in human milk samples collected from different regions of Australia during 2002/2003. For samples collected in 1993 and analysed as pools, the mean level, expressed as TEQ(DFP) was 16+/-1.4 pg TEQ g(-1) lipid. The average lipid content was 3.9+/-0.7%., Conclusion: The levels of PCDDs, PCDFs and dioxin-like PCBs in the human milk of Australian women are both low compared to international levels and similar across all regions of Australia. Consistent with world-wide trends, the levels of PCDDs, PCDFs and dioxin-like PCBs have decreased over a 10 year period from 1993 to 2003 by approximately 40%.