Tea is one of the most widely consumed beverages in the world. However, the association between tea and risk of pancreatic adenocarcinoma remains controversial. This study aimed to investigate the causal relationship between tea consumption and risk of pancreatic adenocarcinoma and to explore their mediating effects. The two-sample Mendelian randomisation (MR) analysis showed an inverse causal relationship between tea intake and pancreatic adenocarcinoma (OR: 0·111 (0·02, 0·85), P < 0·04). To examine the mediating effects, we explored the potential mechanisms by which tea intake reduces the risk of pancreatic adenocarcinoma. Based on the oral bioavailability and drug-like properties in Traditional Chinese Medicine Systems Pharmacology database, we selected the main active ingredients of tea. We screened out the fifteen representative targeted genes by Pharmmapper database, and the gene ontology enrichment analysis showed that these targeted genes were related to vascular endothelial growth factor (VEGF) pathway. The two-step MR analysis of results showed that only VEGF-D played a mediating role, with a mediation ratio of 0·230 (0·066, 0·394). In conclusion, the findings suggest that VEGF-D mediates the effect of tea intake on the risk of pancreatic adenocarcinoma.

The Dispute Settlement Mechanism (DSM), once regarded as the jewel in the crown of the World Trade Organization (WTO), has been facing a variety of serious criticisms for its inherent limitations and problems while its appellate review function has been paralyzed. Discussions on the reform of the WTO DSM have been under way for several years now. Many key items are on the reform agenda, one of which is to introduce Alternative Dispute Resolution (ADR) proceedings to the WTO DSM. Among several options of ADR, ‘mediation’ can offer an important set of tools for the WTO and its Members to resolve disputes in a more efficient and prompt manner. If properly structured, mediation can complement the existing binding proceedings of panels and the Appellate Body. At the same time, introduction of mediation to the WTO DSM may also cause additional legal and practical problems. It may cause further delays, confidentiality traps, due process myriads, and enforcement loopholes. It is vital to introduce mediation provisions to address those critical problems. Systematized and structuralized mediation in the WTO DSM will be able to offer a viable alternative path to resolve certain complex and sensitive disputes.

The analysis of ‘moderation’, ‘interaction’, ‘mediation’ and ‘longitudinal growth’ is widespread in the human sciences, yet subject to confusion. To clarify these concepts, it is essential to state causal estimands, which requires the specification of counterfactual contrasts for a target population on an appropriate scale. Once causal estimands are defined, we must consider their identification. I employ causal directed acyclic graphs and single world intervention graphs to elucidate identification workflows. I show that when multiple treatments exist, common methods for statistical inference, such as multi-level regressions and statistical structural equation models, cannot typically recover the causal quantities we seek. By properly framing and addressing causal questions of interaction, mediation, and time-varying treatments, we can expose the limitations of popular methods and guide researchers to a clearer understanding of the causal questions that animate our interests.

It is such a treat and a privilege to have been at the “Defining Health Law for the Future” symposium and to have met Charity’s family. She was dear to me.

This true story of a mediation in a personal injury lawsuit describes a sequence of events and fairly common practices that raise significant questions about mediation ethics as well as attorney ethics.

Essential minerals are cofactors for synthesis of neurotransmitters supporting cognition and mood. An 8-week fully-blind randomised controlled trial of multinutrients for attention-deficit/hyperactivity disorder (ADHD) demonstrated three times as many children (age 6–12) had significantly improved behaviour (‘treatment responders’) on multinutrients (54 %) compared with placebo (18 %). The aim of this secondary study was to evaluate changes in fasted plasma and urinary mineral concentrations following the intervention and their role as mediators and moderators of treatment response. Fourteen essential or trace minerals were measured in plasma and/or urine at baseline and week eight from eighty-six participants (forty-nine multinutrients, thirty-seven placebos). Two-sample t tests/Mann–Whitney U tests compared 8-week change between treatment and placebo groups, which were also evaluated as potential mediators. Baseline levels were evaluated as potential moderators, using logistic regression models with clinical treatment response as the outcome. After 8 weeks, plasma boron, Cr (in females only), Li, Mo, Se and vanadium and urinary iodine, Li and Se increased more with multinutrients than placebo, while plasma phosphorus decreased. These changes did not mediate treatment response. However, baseline urinary Li trended towards moderation: participants with lower baseline urinary Li were more likely to respond to multinutrients (P = 0·058). Additionally, participants with higher baseline Fe were more likely to be treatment responders regardless of the treatment group (P = 0·036.) These results show that multinutrient treatment response among children with ADHD is independent of their baseline plasma mineral levels, while baseline urinary Li levels show potential as a non-invasive biomarker of treatment response requiring further study.

South African municipalities are entrusted to perform various functions, including providing basic services to communities. Recently, the auditor-general has raised concern about municipalities’ overall functionality and ability to fulfil their obligations. Municipalities’ service delivery failures have led to disputes between them and their communities. Moreover, South African courts have drawn attention to the impact of service delivery failures and described their catastrophic and devastating effects on communities and their local economies. In addition, it is said that the consequences of these municipal failures are more severe for the communities than any other stakeholder. For this reason, communities require legal options to resolve such disputes. This article puts forward two legal options (and potentially a third) to which communities can turn. The article examines mediation and structural interdicts and argues why these options are suitable methods for resolving disputes between a community and its municipality.

Chronic pain affects 20-30% of people worldwide(1). While the impact of nutrition and dietary patterns on bodily pain has gained attention in recent years, the underlying linking mechanisms remain poorly understood; it is possible that body weight, specifically adiposity, may be a mediating factor(2). Thus, the primary aim of this study was to explore whether adiposity mediates the relationship between diet quality and bodily pain. This cross-sectional analysis included 654 adults (57% women, mean age 50.4 ± 1.1 years, BMI 29.0 ± 6.2 kg/m2) with complete diet, adiposity, and pain measures from the Whyalla Intergenerational Study of Health (2008-09). Diet quality was calculated using the Dietary Guideline Index (DGI total score, core and non-core scores)(3), and pain assessed via the Short Form-36 bodily pain scale (SF36-BPS) transformed percent score. Adiposity was determined from body mass index (BMI), waist circumference (WC), and body fat percent (BF, via dual energy x-ray absorptiometry). Mediation analyses determined the role of adiposity in the direct and indirect relationships between diet quality and pain in the whole population, then stratified by sex (self-report). There were no significant indirect or direct effects between DGI total scores and SF36-BPS, for any measure of adiposity. Direct effects were observed for DGI core-food scores on SF36-BPS for each measure of adiposity (BMI, β = 0.258, 95% CI 0.048, 0.467; WC β = 0.246, 95% CI 0.037, 0.455; BF β = 0.247, 95% CI 0.040, 0.454; all p<0.05). Each measure of adiposity accounted for <10% of the relationship between diet quality and pain, with a better-quality diet associated with less bodily pain (higher SF36-BPS). Relationships differed by sex; with no direct or indirect effects seen between DGI scores and SF36-BPS for men while, in women, there was non-mediation with direct positive effects between DGI total score and SF36-BPS for each measure of adiposity (BMI, β = 0.362, 95% CI 0.132, 0.591; WC β = 0.345, 95% CI 0.116, 0.574; BF β = 0.357, 95% CI 0.130, 0.584; all p<0.05). Also in women, body fat mediated 85% of the relationship between DGI non-core scores on bodily pain (indirect effect β=-0.242, 95% CI −0.358, −0.126, p <0.05). While adiposity did not mediate the relationship between diet quality and pain, this study highlights that diet quality plays a role in the pain experience with higher consumption of core foods showing direct associations with lower levels of bodily pain. Moreover, sex differences were observed, with less bodily pain in women associated with higher overall diet quality. Interestingly, body fat drove the relationship between higher pain scores and greater consumption of non-core foods (discretionary), but body fat alone was associated with consumption of fewer discretionary foods. This anomaly requires further investigation.