Triclosan Disrupts Thyroid Hormones: Mode-of-Action, Developmental Susceptibility, and Determination of Human Relevance

Preliminary study demonstrated that triclosan (TCS), a bacteriostat in myriad consumer products, decreases serum thyroxine (T4) in rats. Adverse neurodevelopmental consequences result from thyroid hormone (TH) disruption; therefore determination of whether TCS disrupts THs during development, its mode-of-action (MOA), and the human relevance is critical. This research tested the hypothesis that TCS disrupts THs via activation of pregnane X and constitutive androstane receptors (PXR, CAR), mediating Phase I-II enzyme and hepatic transporter expression and protein changes, thereby increasing catabolism and elimination of THs, resulting in decreased TH concentrations. For Aim One, the hypothesized MOA was assessed using weanling female Long-Evans rats orally exposed to TCS (0-1000 mg/kg/day) for four days. Serum T4 decreased 35% at 300 mg/kg/day. Activity and expression of markers of Phase I (Cyp2b, Cyp3a1) and Phase II (Ugt1a1, Sult1c1) metabolism were moderately induced, consistent with PXR and/or CAR activation and increased hepatic catabolism. Susceptibility of dams and developing rats to TCS-induced hypothyroxinemia was determined for Aim Two. Long-Evans dams received TCS (0-300 mg/kg/day) orally from gestational day (GD) 6 to postnatal day (PND) 21; tissues were collected from fetuses (GD20), pups (PND4, 14, 21), and dams (GD20, PND22). Serum T4 decreased 30% in GD20 dams and fetuses, PND4 pups, and PND22 dams (300 mg/kg/day). Minor increases in activity and expression of markers of hepatic Phase I (Cyp2b, Cyp3a) and Phase II (T4-glucuronidation in PND22 dams) metabolism were consistent with PXR/CAR activation and concomitant minor decreases in T4. For Aim Three, cell-based rat and human PXR and CAR reporter assays were employed to evaluate the human relevance of the putative MOA. TCS (10-30 μM) demonstrated human receptor reporter activities: inverse agonism of CAR1 and agonism of CAR2 CAR3, and PXR. TCS was an inverse agonist of rat CAR, similar to compounds that increase Phase I-II metabolism downstream. Although the data indicate potential species differences in the initiating key event, downstream effects on hepatic catabolism may be similar due to overlapping transcriptional regulatory functions of PXR and CAR. These data establish a plausible MOA for TCS-induced hypothyroxinemia in rats and demonstrate initiation of the MOA in human models

Prejudice and the Brexit vote: a tangled web

The decision of the UK public in July 2016 to vote to leave the European Union was greeted with surprise within the UK and across the world. However, should we really have been surprised? Surveys of attitudes towards freedom of movement to the UK over the last 10 years have suggested an increasing negativity regarding immigration, and many debates before and after the vote have raised the issue of whether prejudice played a role in the outcome of the referendum. It is only within the last 12 months that a number of research study findings have started to provide a more coherent, data-informed evidence-base suggesting that voting behaviour in the referendum may have correlates to prejudice personality styles, nationalism, Islamophobia, and implicit/explicit prejudice. We argue that recent evidence suggests that levels of prejudice towards ‘others’ was a factor in the Brexit vote and that the attitudes underlying this vote must be explored in greater detail through cross-disciplinary scientific research, with legitimate concerns recognised and fallacies challenged

Right-Wing Authoritarian and Explicit Prejudice Attitude Responses to the Paris Terror Attacks: A Within-Subjects Analysis

When a terror attack occurs people appear to be prepared, in the short term, to be more accepting of authoritarian sanctions against outgroup members, particularly if sanctions are targeted against members of the outgroup perceived as responsible for the attack. The current study examined 42 British participants’ scores on measures of Right wing authoritarianism (RWA) and explicit prejudice (EP) before, within 36 hours of, and one year after the November 2015 Paris terror attacks. As higher scores on RWA measures have been linked to considering the world as dangerous and threatening, and desiring that authority control and punish transgressors of societal norms, and higher EP scores have been linked to negative perceptions of outgroups, we hypothesized that participants’ scores on both measures would increase immediately after the terror attack. Analyses showed small but significant increases in RWA and EP scores immediately after the attacks, particularly for those initially scoring lower on these measures, but scores on both measures had returned to baseline levels one year later. These findings from a within-subjects sample support recent between-subjects research suggesting that RWA and EP attitudes are impacted in the short term by reported terrorist attacks

Modeling Ecological Risk, Health Promotion, and Prevention Program Effects for Rural Adolescents

Objective: Universal prevention programs such as Positive Action (PA) mitigate risk factors and enhance promotive factors, often leading to improved adolescent functioning and school climate. The current study used 5 waves of data to assess the impact of PA on adolescent mental health and perceptions of school climate 1 year after completion of the program in a sample of low-income, rural youth. Method: Following multiple imputation and propensity score analysis, we ran 4 (2-level) hierarchal linear models to examine program effects. Results: PA program participants reported significant increases in self-esteem and significant decreases in school hassles relative to youths who did not participate in PA. Participation in PA did not have a significant impact on internalizing symptoms or aggression. Risk factors across the adolescents’ ecology had a strong negative impact on the outcomes, and some promotive factors modestly bolstered adolescent functioning. Conclusions: Findings highlight the influence that risk factors—especially negative interpersonal conflicts—have on adolescent outcomes and indicate that, although PA can help improve adolescents’ perceptions of themselves and their school climate, the program might need to be tailored for use in low-income, rural areas

Queensland SharkSmart Drone Trial Final Report

Remotely Piloted Aircraft Systems, commonly called drones, provide a high-definition aerial view of a wide expanse of ocean, allowing the detection of potentially dangerous sharks in real-time, whilst having a negligible impact on the environment and non-target species. In addition, they are capable of spotting a range of marine hazards and can assist in beach rescue operations, thus providing numerous safety benefits for water users. The beaches of South-East Queensland (SEQ) have relatively good water clarity and a high level of visitation, making them an ideal location to test drones for detecting sharks and improving the safety of water users (Cardno, 2019). North Queensland beaches typically have lower water clarity, although it is important to test drones under these conditions to assess whether they can be effective at detecting sharks. The Queensland SharkSmart drone trial commenced on 19 September 2020, as a partnership between the Queensland Government Department of Agriculture and Fisheries (DAF) and Surf Life Saving Queensland (SLSQ). The trial was part of the Queensland Government’s commitment to research and trialling alternatives to traditional shark control measures. Drones were operated at two beaches on the Sunshine Coast (Alexandra Headland and Coolum North), two beaches on the Gold Coast (Southport Main Beach and Burleigh Beach) and one beach on North Stradbroke Island (NSI; Ocean beach) between 19 September 2020 and 4 October 2021. Additionally, to assess the effectiveness of drones at detecting sharks under the different environmental conditions found at North Queensland (NQ) beaches, drones were operated at Palm Cove, Cairns and Alma Bay, Magnetic Island, from 26 June 2021 to 31 October 2021. Drones were operated on weekends, public holidays and school holidays by SLSQ pilots, with two flights per hour from approximately 8am until midday. Flights lasted 15 - 20 minutes and followed a 400 m transect behind the surf break. All footage was collected in 4K and securely archived for later analysis with key operational and environmental data collected for every flight. When a shark was sighted, the drone pilot lowered the aircraft to determine the species and size while estimating distance of the animal from water users. Data analysis quantified the numbers of sharks sighted at each beach and the rate of sightings as a percentage across the whole trial from 19 September 2020 to 31 October 2021. Generalised Linear Mixed Models (GLMMs) were applied to quantify the influence of environmental and operational factors on the sightability (probability of a shark being sighted) of sharks. The movement tracks of sharks were mapped to analyse their behaviour and identify if there was clustering of movements in certain areas. Sighting rates from drones were also compared with shark catch in adjacent nets and drumlines deployed as part of the Queensland Shark Control Program (SCP)

Automatic Detection of Cortical Arousals in Sleep and their Contribution to Daytime Sleepiness

Cortical arousals are transient events of disturbed sleep that occur spontaneously or in response to stimuli such as apneic events. The gold standard for arousal detection in human polysomnographic recordings (PSGs) is manual annotation by expert human scorers, a method with significant interscorer variability. In this study, we developed an automated method, the Multimodal Arousal Detector (MAD), to detect arousals using deep learning methods. The MAD was trained on 2,889 PSGs to detect both cortical arousals and wakefulness in 1 second intervals. Furthermore, the relationship between MAD-predicted labels on PSGs and next day mean sleep latency (MSL) on a multiple sleep latency test (MSLT), a reflection of daytime sleepiness, was analyzed in 1447 MSLT instances in 873 subjects. In a dataset of 1,026 PSGs, the MAD achieved a F1 score of 0.76 for arousal detection, while wakefulness was predicted with an accuracy of 0.95. In 60 PSGs scored by multiple human expert technicians, the MAD significantly outperformed the average human scorer for arousal detection with a difference in F1 score of 0.09. After controlling for other known covariates, a doubling of the arousal index was associated with an average decrease in MSL of 40 seconds ($\beta$ = -0.67, p = 0.0075). The MAD outperformed the average human expert and the MAD-predicted arousals were shown to be significant predictors of MSL, which demonstrate clinical validity the MAD.Comment: 40 pages, 13 figures, 9 table

Mere Measurement “Plus”: How Solicitation of Open-Ended Positive Feedback Influences Customer Purchase Behavior

In two studies (a longitudinal field experiment with an established B2C national chain, and a field experiment with a B2B software manufacturer), we demonstrate that starting a survey with an open-ended positive solicitation increases customer purchase behavior. Study 1, a longitudinal field experiment, showed that one-year following the completion of a survey that began by asking customers what went well during their purchase experience, customers spent 8.25% more than customers who completed a survey that did not include the positive solicitation. In Study 2, we utilized multiple treatment groups to assess the step-wise gains of solicitation, measurement, and solicitation frame. The results demonstrated (a) a mere solicitation effect, (b) a traditional mere measurement effect, and (c) an additional “mere measurement plus” effect of an open-ended positive solicitation; all effects increased customer spending. Specifically, starting a survey with an open-ended positive solicitation resulted in a 32.88% increase in customer spending relative to a survey with no open-ended positive solicitation. The findings suggest that firms can proactively influence the feedback process. Soliciting open-ended positive feedback can create positively biased memories of an experience; the subsequent expression of those memories in an open-ended feedback format further reinforces them, making them more salient and accessible in guiding future purchase behavior

Wild Food:Plants, Fish and Small Animals on the Menu for Early Holocene Populations at al-Khiday, Central Sudan

Al Khiday, located on the bank of the White Nile in Sudan, offers an exceptionally preserved stratigraphic sequence, providing a unique opportunity to use organic residue analysis to investigate diet and subsistence over the full course of the Khartoum Mesolithic together with possible continuity or change into the Early Neolithic, a period of nearly 3000 years (8900-6000 cal BP). Whilst the vast and diverse Mesolithic fish assemblage indicates a strong reliance on products from aquatic habitats, floodplains, vegetated marshes and open water, results from the lipid residue analysis suggest that the fish were not cooked in the pots, likely being consumed in other ways. Rather, pots were more specialised in processing plants, wild grasses, leafy plants and sedges, confirmed by experimental analysis, and for the first time, providing direct chemical evidence for plant exploitation in the Khartoum Mesolithic. Non-ruminant fauna, such as warthog and low lipid-yielding reptiles such as Adanson’s mud turtle and Nile monitor lizard, which were found in significant numbers at al-Khiday, were also cooked in pots. There is little evidence for the processing of wild ruminants in the pots, suggesting either that ruminant species were not routinely hunted, or, that large wild fauna may have been cooked in different ways, possibly grilled over fires. These data suggest sophisticated economic strategies by sedentary people likely exploiting their ecological niche to the fullest. Pottery use changes considerably in the Early Neolithic, with ruminant products being more routinely processed in pots, and while the exploitation of domesticates cannot be confirmed by a small faunal assemblage, some dairying does take place. In summary, our results provide valuable information on Early and Middle Holocene lifeways in central Sudan

Short-term Exposure to Triclosan Decreases Thyroxine In Vivo via Upregulation of Hepatic Catabolism in Young Long-Evans Rats

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)-phenol) is a chlorinated phenolic antibacterial compound found in consumer products. In vitro human pregnane X receptor activation, hepatic phase I enzyme induction, and decreased in vivo total thyroxine (T4) suggest adverse effects on thyroid hormone homeostasis. Current research tested the hypothesis that triclosan decreases circulating T4 via upregulation of hepatic catabolism and transport. Weanling female Long-Evans rats received triclosan (0–1000 mg/kg/day) by gavage for 4 days. Whole blood and liver were collected 24 h later. Total serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured by radioimmunoassay. Hepatic microsomal assays measured ethoxyresorufin-O-deethylase, pentoxyresorufin-O-deethylase (PROD), and uridine diphosphate glucuronyltransferase enzyme activities. The messenger RNA (mRNA) expression of cytochrome P450s 1a1, 2b1/2, and 3a1/23; UGTs 1a1, 1a6, and 2b5; sulfotransferases 1c1 and 1b1; and hepatic transporters Oatp1a1, Oatp1a4, Mrp2, and Mdr1b was measured by quantitative reverse transcriptase PCR. Total T4 decreased dose responsively, down to 43% of control at 1000 mg/kg/day. Total T3 was decreased to 89 and 75% of control at 300 and 1000 mg/kg/day. TSH did not change. Triclosan dose dependently increased PROD activity up to 900% of control at 1000 mg/kg/day. T4 glucuronidation increased nearly twofold at 1000 mg/kg/day. Cyp2b1/2 and Cyp3a1/23 mRNA expression levels were induced twofold and fourfold at 300 mg/kg/day. Ugt1a1 and Sult1c1 mRNA expression levels increased 2.2-fold and 2.6-fold at 300 mg/kg/day. Transporter mRNA expression levels were unchanged. These data denote important key events in the mode of action for triclosan-induced hypothyroxinemia in rats and suggest that this effect may be partially due to upregulation of hepatic catabolism but not due to mRNA expression changes in the tested hepatic transporters

“Do-it-yourself”: Vaccine rejection and complementary and alternative medicine (CAM)

© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (Nov 2017) in accordance with the publisher’s archiving policyIn this article, we elucidate a symbiotic relationship between complementary and alternative medicine (CAM) and rejection of, or hesitancy towards, vaccination. In Fremantle, Western Australia, and Adelaide, South Australia, we conducted in-depth interviews from September 2013–December 2015 with 29 parents who had refused or delayed some or all of their children's vaccines. Our qualitative analysis found that for many, their do-it-yourself ethic and personal agency was enhanced by self-directed CAM use, alongside (sometimes informal) CAM practitioner instruction. Reifying ‘the natural,’ these parents eschewed vaccines as toxic and adulterating, and embraced CAM as a protective strategy for immune systems before, during and after illness. Users saw CAM as harm-free, and when it came to experiences that non-users might interpret as demonstrating CAM's ineffectiveness, they rationalised to the contrary. They also generally glossed over its profit motive. CAM emerged as part of an expert system countering Western medicine. CAM's faces were trusted and familiar, and its cottage capitalism appeared largely free from the taint of “Big Pharma.” A few parents employed a scientific critique of CAM modalities – and a minority were dubious of its profit motive – but others rejected the epistemology underpinning biomedicine, framing CAM as a knowledge not poisoned by avarice; a wisdom whose very evidence-base (anecdote and history) was demeaned by an arrogant scientific process only permitting belief in that which could be quantified. However, all parents engaged with Western medicine for broken bones and, sometimes, medical diagnoses. Our analysis suggests that pro-vaccination health professionals, policymakers and information-providers seeking to address the role of CAM in vaccine rejection face significant challenges due to the epistemic basis of some parents' decisions. However, we make some suggestions for professional practice and policy to enhance trust in vaccination