Sex-dimorphism in human serum endocannabinoid and n-acyl ethanolamine concentrations across the lifespan.

The endocannabinoid (ECB) system has recently been considered a potential treatment target for various clinical disorders. However, research around age- and sex-related changes within the ECB system is relatively limited. To improve our understanding of these changes, the current study measured arachidonoyl ethanolamide (AEA), 2-arachidonoyl glycerol (2-AG), oleoylethanolamine (OEA), palmitoylethanolamine (PEA), arachidonic acid (AA), cortisol, and progesterone in pooled serum samples stratified by sex (male and female) and age groups (5-15; 15-30; 30-45; 45-60; 60-75; 85+), using liquid-chromatography tandem mass spectrometry. Serum progesterone levels significantly increased in females of the 15-30 and 30-45 age groups, before declining. Significantly higher cortisol, AEA, 2-AG, OEA, and PEA were found in males and in older age, while significantly higher AA was found in females. Our results indicate that ECBs and related hormones exhibit sexual dimorphism in the age ranges that correspond with female pregnancy, menopause, and post menopause. Male testosterone levels most likely influences male ECB changes throughout the lifespan. Future research could capitalise on these findings by performing repeated measurements in individuals in a longitudinal style, to further refine the temporal profile of age-specific changes to the ECB system identified here.

What are the precise reasons for the disparity in referrals to fitness to practise between international and UK medical graduates?

PURPOSE OF THE STUDY: To discover the precise reasons for referring a doctor to the Medical Practitioners Tribunal Service, and whether there are any disparities between referrals of international medical graduates and UK graduates. Further to consider whether understanding the precise reasons would provide insight into the nature of referrals. STUDY DESIGN: We collected and analysed the data from the Medical Practitioners Tribunal Service website over a period of 12 months. RESULTS: There were 228 cases of which 142 (62%) were international medical graduates and 86 (38%) were UK graduates. More international medical graduates were referred for professional misconduct, poor performance and lack of adequate English language. The common reasons for professional misconduct were providing sub-optimal care, sexual misconduct and dishonest behaviour. More UK graduates were referred following convictions due to offences related to alcohol intake and financial dishonesty. There is paucity of good quality information to identify the exact reasons for the disparity. CONCLUSION: More international medical graduates were referred to the Medical Practitioners Tribunal Service than UK graduates. There was disparity in the nature of the referrals and we hope our findings will inform employers and the regulatory bodies to understand that comprehensive induction, inclusion, mentoring and adjustments are needed to support international medical graduates to mitigate the risks of failure and help them to meet the required professional standards.

Improving Wastewater-Based Tobacco Use Estimates Using Anabasine.

In wastewater-based epidemiology (WBE), nicotine metabolites have been used as biomarkers for monitoring tobacco use. Recently, the minor tobacco alkaloids anabasine and anatabine have been suggested as more specific biomarkers for tobacco use since nicotine use can be from both tobacco and non-tobacco sources. This study aimed to provide an in-depth evaluation of the suitability of anabasine and anatabine as WBE biomarkers of tobacco and subsequently estimate their excretion factors for WBE applications. Pooled urine (n = 64) and wastewater samples (n = 277), collected between 2009 and 2019 in Queensland, Australia, were analyzed for nicotine and its metabolites (cotinine and hydroxycotinine), as well as anabasine and anatabine. Anabasine performed as the better biomarker, showing a similar per capita load in pooled urine (2.2 ± 0.3 µg/day/person) and wastewater samples (2.3 ± 0.3 µg/day/person), while the per capita load of anatabine in wastewater was 50% higher than its load in urine. It is estimated that 0.9 µg of anabasine was excreted per cigarette smoked. Triangulation of tobacco sales data and tobacco use estimated from either anabasine or cotinine showed that anabasine-based estimates were 5% higher than sales data, while cotinine-based estimates were between 2 and 28% higher. Our results provided concrete evidence to confirm the suitability of anabasine as a specific biomarker for monitoring tobacco use by WBE.

Enabling ambulatory movement in wearable magnetoencephalography with matrix coil active magnetic shielding.

The ability to collect high-quality neuroimaging data during ambulatory participant movement would enable a wealth of neuroscientific paradigms. Wearable magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has the potential to allow participant movement during a scan. However, the strict zero magnetic field requirement of OPMs means that systems must be operated inside a magnetically shielded room (MSR) and also require active shielding using electromagnetic coils to cancel residual fields and field changes (due to external sources and sensor movements) that would otherwise prevent accurate neuronal source reconstructions. Existing active shielding systems only compensate fields over small, fixed regions and do not allow ambulatory movement. Here we describe the matrix coil, a new type of active shielding system for OPM-MEG which is formed from 48 square unit coils arranged on two planes which can compensate magnetic fields in regions that can be flexibly placed between the planes. Through the integration of optical tracking with OPM data acquisition, field changes induced by participant movement are cancelled with low latency (25 ms). High-quality MEG source data were collected despite the presence of large (65 cm translations and 270° rotations) ambulatory participant movements.

Prescribing - a worldwide survey on governance.

PURPOSE OF THE STUDY: To explore the governance regarding prescribing across the world. STUDY DESIGN: We used a web-based questionnaire to ask the doctors about their prescribing practices and perception of governance in relation to prescribing. We sent the questionnaire to all doctors working in our hospital and primarily targeted doctors who had acquired their medical qualifications outside the UK to get a global view. RESULTS: We received 139 responses describing prescribing practices from 40 countries. More than 50% of doctors said there is no restriction in prescribing for themselves and their relatives. A third of them said that they could even prescribe controlled drugs without any restriction. 56% said that one doesn't need a prescription to get antibiotics. When analysed by countries, 80% said that they could self-prescribe and in 50% of the countries, one could get antibiotics without a prescription. CONCLUSIONS: In many countries there is poor governance with regards to prescribing. This is due to a lack of restrictions on prescribing (both self-prescribing and for friends/family) and the public's ability to obtain antibiotics and controlled drugs.

First indication of perfluoroalkyl substances in human serum from Papua New Guinea.

Human biomonitoring programs of per- and polyfluoroalkyl substances (PFAS) have been conducted around the world to assess human exposure and health risk. Inquiry into population PFAS levels in a socioeconomically and geographically unique region such as the Pacific Island Papua New Guinea, may provide new insights into PFAS exposure pathways and sources. This study presented the first indication of PFAS exposure in the Papua New Guinea population. De-identified serum samples were pooled from surplus pathology serum samples collected between 2019 and 2020. A total of 11 PFAS were detected in the serum pools including 10 perfluoroalkyl acids (PFAA) and 9Cl-F53B (a perfluorooctane sulfonic acid - PFOS alternative). The observed PFAA profile was somewhat similar to that observed for general population data of other countries such as Australia, Malaysia, and Canada suggesting similar exposure sources and/or pathways. However, PFAS concentrations were consistently lower than concentrations in the serum measured in pools obtained from Australia. The detection of 9Cl-F53B in all pools was a new finding which might be related to exposure from locally industrial sources.

Natural Exposure- and Vaccination-Induced Profiles of Ex Vivo Whole Blood Cytokine Responses to Coxiella burnetii.

Q fever is a zoonotic disease caused by the highly infectious Gram-negative coccobacillus, Coxiella burnetii (C. burnetii). The Q fever vaccine Q-VAX® is characterised by high reactogenicity, requiring individuals to be pre-screened for prior exposure before vaccination. To date it remains unclear whether vaccine side effects in pre-exposed individuals are associated with pre-existing adaptive immune responses to C. burnetii or are also a function of innate responses to Q-VAX®. In the current study, we measured innate and adaptive cytokine responses to C. burnetii and compared these among individuals with different pre-exposure status. Three groups were included: n=98 Dutch blood bank donors with unknown exposure status, n=95 Dutch village inhabitants with known natural exposure status to C. burnetii during the Dutch Q fever outbreak of 2007-2010, and n=96 Australian students receiving Q-VAX® vaccination in 2021. Whole blood cytokine responses following ex vivo stimulation with heat-killed C. burnetii were assessed for IFNγ, IL-2, IL-6, IL-10, TNFα, IL-1ß, IP-10, MIP-1α and IL-8. Serological data were collected for all three cohorts, as well as data on skin test and self-reported vaccine side effects and clinical symptoms during past infection. IFNγ, IP-10 and IL-2 responses were strongly elevated in individuals with prior C. burnetii antigen exposure, whether through infection or vaccination, while IL-1ß, IL-6 and TNFα responses were slightly increased in naturally exposed individuals only. High dimensional analysis of the cytokine data identified four clusters of individuals with distinct cytokine response signatures. The cluster with the highest levels of adaptive cytokines and antibodies comprised solely individuals with prior exposure to C. burnetii, while another cluster was characterized by high innate cytokine production and an absence of C. burnetii-induced IP-10 production paired with high baseline IP-10 levels. Prior exposure status was partially associated with these signatures, but could not be clearly assigned to a single cytokine response signature. Overall, Q-VAX® vaccination and natural C. burnetii infection were associated with comparable cytokine response signatures, largely driven by adaptive cytokine responses. Neither individual innate and adaptive cytokine responses nor response signatures were associated retrospectively with clinical symptoms during infection or prospectively with side effects post-vaccination.

Characterization of glyphosate and AMPA concentrations in the urine of Australian and New Zealand populations.

Glyphosate is the most used herbicide globally, but our understanding of human exposure and how different uses affect exposure is not well understood. The aim of this study was to obtain the first data on glyphosate and its primary degradation product aminomethylphosphonic acid (AMPA) concentrations in pooled and individual urine from the Australia and New Zealand region using a sensitive direct injection method and compare results with studies from elsewhere. Pooled urine samples from the Australian general population (n = 125 pools representing >1875 individuals) and individual urine samples (n = 27) from occupationally exposed New Zealand farmers were analysed by LC-MS/MS. Glyphosate was detected above the LOD (0.20-1.25 µg/L) in 8 % of the Australian population pooled urine samples with most detections in the 45-60 years age group. Furthermore, glyphosate (0.85 to 153 µg/L) and AMPA (0.50 to 3.35 µg/L) were detected in 96 % and 33 % of farmers, respectively. The maximum glyphosate urine concentration was 1.7 times above the recommended acceptable daily intake (ADI), when assuming a urinary excretion rate of 1 %. The pooled sampling and analysis approach proved effective for rapid large-scale screening of populations and could be used to determine where targeted and more specific individual sampling may be required.

Biomonitoring of per- and polyfluoroalkyl substances (PFAS) exposure in firefighters: Study design and lessons learned from stakeholder and participant engagement.

Firefighters may be occupationally exposed to per- and polyfluoroalkyl substances (PFASs) through Aqueous Film-Forming Foam (AFFF), smoke, dust and turnout gear, in addition to other background exposure sources. Epidemiological assessment of PFAS exposure in an occupational cohort of firefighting staff commenced in 2013-2014, following cessation of PFAS-based AFFF in Australian aviation. Here we present the study design and methodology of a follow-up study conducted in 2018-2019. We focus on our experiences engaging with stakeholders and participants with the establishment of an inclusive study group and highlight the key lessons learned from implementing a co-design process in the study. The study included a cross-sectional assessment of blood serum concentrations of 40 PFASs, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS), and 14 health-related biomarkers in 799 current and former Aviation Rescue Firefighting Services employees. A large proportion (87%) of the participants from the preliminary exposure study in 2013-2014 were re-recruited in the follow-up study. This enabled further longitudinal analyses in this subset of 130 participants. Participants included employees from different work roles and timeframes, reflecting the periods when three different firefighting foams were utilised in Australia. Establishment of a collaborative and inclusive study group (including stakeholders and participants) contributed to several components of the study design, including the expansion of robust analytical quality assurance and control measurements, and tailoring of communication and dissemination strategies. These outcomes were key factors that improved transparency of the research design, methods and results. Additionally, implementing elements of co-design helped build trust between researchers and participants, which is an important consideration for studies funded by stakeholders related to the exposure source.

Risk and incidence of cognitive impairment in patients with chronic kidney disease and diabetes: the results from a longitudinal study in a community cohort of patients and an age and gender-matched control cohort in North Wales, UK.

OBJECTIVES: The aim of the current investigation is to estimate the incidence and risk for neurocognitive disorders (NCD) in a chronic kidney disease (CKD) cohort with diabetes, compared with an age and sex-matched control cohort. DESIGN: Longitudinal follow-up. SETTING: District general hospital North Wales, UK. PARTICIPANTS: Ninety-two patients with CKD and an age and gender-matched sample of 143 controls at baseline and at approximately 36 months. INTERVENTIONS: Cognitive function was assessed in the patients with CKD (mean age 75.8±9.1; 49 men: 43 women) and the control cohort (mean age 74.4±6.2; 71 men: 72) at baseline and at approximately 36 months. An NCD diagnosis was based on patient, informant, case note review, neuropsychological assessment and application of Diagnostic and Statistical Manual of Mental disorders V.5 (DSM-5) for an NCD and Petersen's criteria for mild cognitive impairment. RESULTS: Follow-up neuropsychological assessment and application of DSM-5 criteria of the cognitively normal patients and controls revealed, 25/92 (27%) of the CDK and 20/143 (13.9%) in the control cohort developed an NCD. The CKD cohort had a twofold increased risk for the development of an NCD compared with the controls, adjusted for age and sex. The incidence rate for an NCD in the CKD cohort was 10.5 and 5.1 in the controls, respectively. No association was observed with the stage of CKD and cognitive function. CONCLUSIONS: This longitudinal investigation found that patients with CKD have a twofold increased risk for the development of an NCD. The current investigation highlighted the need to recognise that NCD in patients with CKD is a common comorbidity and that they are at a much higher risk for the development of a significant neurodegenerative disorders. In view of these risks, neuropsychological screening and assessment should be incorporated into normal CKD clinical practice and management.

Benthic cyanobacteria: A utility-centred field study.

Although there is growing evidence that benthic cyanobacteria represent a significant source of toxins and taste and odour (T&O) compounds in water bodies globally, water utilities rarely monitor for them. Benthic cyanobacteria grow in an array of matrices such as sediments, biofilms, and floating mats, and they can detach and colonize treatment plants. The occurrence of compounds produced by benthic species across matrix and climate types has not been systematically investigated. Consequently, there is a lack of guidance available to utilities to monitor for and mitigate the risk associated with benthic cyanobacteria. To assess toxin and T&O risk across climatic zones and provide guidance to water utilities for the monitoring of benthic mats, two field surveys were conducted across three continents. The surveys examined the occurrence of six secondary metabolites and associated genes, namely, geosmin, 2-methylisoborneol (MIB), anatoxin-a, saxitoxin, microcystin, and cylindrospermopsin, in benthic environmental samples collected across three climates (i.e., temperate, sub-tropical, and tropical) and a range of matrix types. Existing enzyme-linked immunosorbent assays (ELISAs) and qPCR assays and were used to measure compound concentrations and their associated genes in samples. A novel qPCR assay was designed to differentiate the production of MIB by actinobacteria from that of cyanobacteria. MIB occurrence was higher in warmer climates than temperate climates. Cyanobacteria in benthic mats were the major producers of taste and odour compounds. Floating mats contained significantly higher concentrations of geosmin and saxitoxins compared to other matrix types. Samples collected in warmer areas contained significantly more saxitoxin and cylindrospermopsin than samples collected in temperate climates. While these trends were mainly indicative, they can be used to establish monitoring practices. These surveys demonstrate that benthic mats are significant contributors of secondary metabolites in source water and should be monitored accordingly. Benthic cyanobacteria were the sole producers of T&O in up to 17% of the collected samples compared to actinobacteria, which were sole producers in only 1% of the samples. The surveys also provided a platform of choice for the transfer of methodologies and specific knowledge to participating utilities to assist with the establishment of monitoring practices for benthic cyanobacteria and associated secondary metabolites.

Innovative method of utilising hydrogen peroxide for source water management of cyanobacteria.

The treatment and control of cyanobacterial blooms using copper-based algaecides in water reservoirs have historically been used; however, due to the adverse impact of copper on the environment, water authorities have been researching and studying new and innovative ways to control cyanobacterial blooms. Hydrogen peroxide has been investigated as an environmentally friendly alternative, and this research aims to determine the impact of water quality on its effectiveness based on the decay characteristics in different water samples. Natural water samples from South Australian reservoirs and river were used to evaluate hydrogen peroxide decomposition and provide a better strategy for water operators in using it as an algaecide. Our experiments show the dependency of hydrogen peroxide decomposition not only on water quality but also on the initial hydrogen peroxide dose. A higher initial hydrogen peroxide dose can trigger the increase of pH, leading to increased consumption of hydrogen peroxide. In addition, the hydrogen peroxide decomposition is significantly accelerated with the rise of copper concentration in water samples. Moreover, it is found that UV light can also affect the decomposition rate of hydrogen peroxide. The hydrogen peroxide decay is more significant under UV light for the samples with lower hydrogen peroxide concentrations. Our study also shows the impact of dissolved organic carbon (DOC) on hydrogen peroxide decomposition is not substantial. The study also presents a modelling method to optimise hydrogen peroxide application based on water quality characteristics. Our findings can provide knowledge for the water industry to produce a suitable model which can be used to optimise the application of hydrogen peroxide for the control of cyanobacteria.

Structured hypertension education program for people with type 2 diabetes, the SHED study.

OBJECTIVES: There is enough evidence that patient education and lifestyle modification has shown benefits in diabetes care, however the evidence is less for improving care of hypertension. Our study is the first in the UK to assess the impact of a structured hypertension education program in subjects with type 2 diabetes. DESIGN: Prospective randomised controlled study. SETTING AND INTERVENTION: From a diabetes clinic in a district and general hospital in UK 132 participants were equally randomised into intervention group and control group. Intervention included a once weekly education session for 4 weeks together with home blood pressure monitoring and dose changes in antihypertensives. Base line data was recorded with follow up after 3 and 6 months. RESULTS: More participants achieved target BP in the intervention group versus control. This difference appeared early at the 3rd months (48.8% versus 20.4% respectively, p = 0.007) and remained at the 6th month (58.1% versus 20.4% respectively, p < 0.001). The change in number of pills was significantly lower in the intervention group. The mean increase in antihypertensive pills was 0.22 ± 0.48 (13 ± 30% increase) in the intervention group versus 0.62 ± 0.68 (41 ± 60% increase) in the routine group (p = 0.014), denoting less need to escalate treatment. CONCLUSION: We demonstrated that our structured education program has led to a significantly higher percentage of participants achieving the BP target, early after intervention, together with a significant reduction in the number of antihypertensive pills.

Biodiversity policy beyond economic growth.

Increasing evidence-synthesized in this paper-shows that economic growth contributes to biodiversity loss via greater resource consumption and higher emissions. Nonetheless, a review of international biodiversity and sustainability policies shows that the majority advocate economic growth. Since improvements in resource use efficiency have so far not allowed for absolute global reductions in resource use and pollution, we question the support for economic growth in these policies, where inadequate attention is paid to the question of how growth can be decoupled from biodiversity loss. Drawing on the literature about alternatives to economic growth, we explore this contradiction and suggest ways forward to halt global biodiversity decline. These include policy proposals to move beyond the growth paradigm while enhancing overall prosperity, which can be implemented by combining top-down and bottom-up governance across scales. Finally, we call the attention of researchers and policy makers to two immediate steps: acknowledge the conflict between economic growth and biodiversity conservation in future policies; and explore socioeconomic trajectories beyond economic growth in the next generation of biodiversity scenarios.

Urinary Concentrations of Bisphenols in the Australian Population and Their Association with the Per Capita Mass Loads in Wastewater.

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.

Evaluating age and temporal trends of chlorinated paraffins in pooled serum collected from males in Australia between 2004 and 2015.

Chlorinated paraffins (CPs) are high production volume chemicals of which some show resistance to environmental degradation, long-rang transport, bioaccumulation and toxicity potential. Information regarding their presence in humans is limited, including their human bioaccumulation potential. The present study aimed to evaluate CP levels in human serum from Australia in order to better understand their exposure and current pollution status as well as trends associated with age and time between 2004 and 2015. For this, we selected a male sub-group of the Australian population under 60 years old (n = 16 pools, total 1600 serum samples). While long-chain CP (C18-20) and most short-chain CP (C10-13, SCCPs) levels were below method detection limits (MDL), medium-chain CPs (C14-17, MCCPs) were found in most serum samples (detection frequency 94%) as well as CPs with a carbon chain length of nine (detection frequency 76%). The levels of ΣSCCPs and ΣMCCPs ranged from

Concentrations of phthalate metabolites in Australian urine samples and their contribution to the per capita loads in wastewater.

Exposure to phthalates is a public health concern. In this study, we collected both urine and wastewater samples from 2012 to 2017 and analysed for 14 phthalate metabolites to assess human exposure to phthalates in Southeast Queensland (SEQ), and for associations between phthalate metabolites in urine and wastewater samples. Twenty-four pooled urine samples were prepared from 2400 individual specimens every two years (stratified by age, gender and collection year). Wastewater samples were collected from the three major wastewater treatment plants (WWTPs) representing locations in the SEQ region including a regional city, part of the state capital city and a third major urban WWTP in the region. Over the period, decreases for most phthalate metabolites, i.e. mono-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), monocyclohexyl phthalate (MCHP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and monomethyl phthalate (MMP), but an increase in monoethyl phthalate (MEP, particularly in young children) were observed in urine. In general, temporal changes were smaller in urine pools representing older age groups. We also found substantial variation in per capita mass loads of phthalate metabolites between samples from the three WWTPs with generally higher concentrations of most phthalates in the metropolitan areas. Per capita mass loads of most phthalate metabolites in wastewater were higher than would be expected from the per-capita excretion in urine, suggesting there are additional sources contributing to the majority of the observed phthalate metabolites in wastewater. For MEHHP and MEOHP we estimate that the urinary excretion accounts for a substantial fraction (average about 50%) of the mass load observed in the wastewater hence wastewater data may provide useful for monitoring trends in exposure.

Removal of microcystins from a waste stabilisation lagoon: Evaluation of a packed-bed continuous flow TiO2 reactor.

Photocatalysis has been shown to successfully remove microcystins (MC) in laboratory experiments. Most research to date has been performed under ideal conditions in pure or ultrapure water. In this investigation the efficiency of photocatalysis using titanium dioxide was examined in a complex matrix (waste stabilisation lagoon water). A flow-through photocatalytic reactor was used for the photocatalytic removal of four commonly occurring microcystin analogues (MC-YR, MC-RR, MC-LR, and MC-LA). Up to 51% removal for single MC analogues in waste lagoon water was observed. Similar removal rates were observed when a mixture of all four MC analogues was treated. Although treatment of MC-containing cyanobacterial cells of Microcystis aeruginosa resulted in no decline in cell numbers or viability with the current reactor design and treatment regime, the photocatalytic treatment did improve the overall quality of waste lagoon water. This study demonstrates that despite the presence of natural organic matter the microcystins could be successfully degraded in a complex environmental matrix.