We report the results of two experiments designed to better understand the mechanisms driving decision-making under ambiguity. We elicit individual preferences over different sources of uncertainty, entailing different degrees of complexity, from subjects with different sophistication levels. We show that (1) ambiguity aversion is robust to sophistication, but the strong relationship previously reported between attitudes toward ambiguity and compound risk is not. (2) Ellsberg ambiguity attitude can be partly explained by attitudes toward complexity for less sophisticated subjects only. Overall, regardless of the subject's sophistication level, the main driver of Ellsberg ambiguity attitude is a specific treatment of unknown probabilities.
To assess the effectiveness of self-help interventions in reducing work disability and improving work- and health-related outcomes among individuals with musculoskeletal, anxiety, and/or depressive conditions; to explore lived experiences with self-help interventions; and to integrate quantitative and qualitative findings to guide future research and implementation. We conducted a rapid mixed methods systematic review following World Health Organization (WHO) and Cochrane Rapid Reviews Methods Group guidance. We included randomized controlled trials (RCTs), quasi-experimental, qualitative, and mixed methods studies published in English since 2007. Eligible studies evaluated self-help interventions targeting musculoskeletal, anxiety, and/or depressive conditions in working-age adults (18–65 years). Quantitative outcomes included functioning, return-to-work, productivity, and self-efficacy; qualitative outcomes reflected user experiences. Risk of bias was assessed using RoB 2, ROBINS-I, and CASP tools. Findings were synthesized narratively by intervention types and outcome domain. Eight studies met inclusion criteria: five RCTs, two quasi-experimental, and one qualitative. All seven quantitative studies were rated high risk of bias. Short-term improvements were observed in disability and physical quality of life in two exercise-based trials, but effects on work participation were inconsistent and generally below thresholds for clinical importance. Cognitive-behavioral and psychoeducational programs produced small improvements in self-efficacy and presenteeism, and relaxation and educational interventions showed no meaningful effects. The qualitative study highlighted workplace barriers such as productivity pressures and limited opportunities for movement that constrained engagement. Self-help interventions may modestly improve self-management, disability, and coping in the short term but show limited and inconsistent evidence for reducing work disability. Their effectiveness likely depends on adherence, contextual support, and integration into workplace environments. Future high-quality, co-designed, context-sensitive studies are needed to clarify effectiveness, safety, and sustainability in real-world settings. PROSPERO registration: CRD42023472934, registered on October 16, 2023; modified March 17 2025.
Musculoskeletal health is essential to health, well-being, and independence across the life course. Musculoskeletal conditions including inflammatory joint diseases, osteoarthritis, back pain, osteoporosis, and fragility fractures are among the greatest causes of disability globally imposing a major burden on health and social care and economic impact also through lost productivity. Despite effective ways of preventing, treating, and rehabilitating these problems, lack of priority results in avoidable disability and costs. We consider how the expert community, through lived and learnt experience, can together influence health policy and health priorities, nationally and globally.
Toll-like receptor 4 (TLR4) is a membrane receptor linked to cardiomyocyte injuries. If activated, TLR4 starts a signaling cascade via recruitment of the myeloid differentiation primary response 88 (MyD88) protein, leading to the phosphorylation of nuclear factor-κB (NFκB) and production of pro-inflammatory cytokines, which fuels the initiation of the cardiac injury. Betanin is a beet-betacyanin that ameliorates organ toxicities via mitigating the cytokine amplification. Molecular docking was done to test TLR4 as a plausible target for betanin and a bioinformatic search elucidated any potential relationship between betanin and TLR4 pathways including those implicated in inflammatory responses and cardiotoxicity. Further, an experimental study used male albino mice were divided equally into 3 groups as 1) Vehicle, 2) Capecitabine and 3) Capecitabine + Betanin (100 mg/kg/day) groups. Capecitabine (200 mg/kg) was given 5 times a week for 3 weeks. Frozen heart samples were processed for ELISA assays for MyD88/NFκB proteins. Formalin-fixed heart samples were used for histopathologic staining using the iron-hematoxylin stain. The bioinformatic analysis confirmed the relationship between myocardial injury and TLR4 signaling. Molecular docking indicated the ability of betanin to block the TLR4 receptors. In the mouse study, betanin mitigated the cardiac histopathological finding, reduced the serum level of cardiac enzymes and downregulated the protein level of MyD88/NFκB. This study highlighted that betanin acts as a putative inhibitor for TLR4. Betanin mitigated capecitabine induced myocardial injury and suppressed the TLR4/MyD88/NFκB signaling. Hence, betanin was identified as a candidate for further investigation in mitigating myocardial injury.
Climate change poses significant risks to the global labour force, as rising temperatures undermine both work capacity and health. This study investigates the feedbacks between temperature extremes and labour productivity and the role of increased energy consumption as a form of adaptation over the long run. We find that climate-induced labour impacts generate considerable losses and rising adaptation costs even under a moderate (SSP2) warming scenario, with global GDP falling by 2.9% per year by 2100. Results are robust in showing how the negative effect on labour significantly penalises highly exposed economies in the Global South, where exposure to rising temperature is highest and adaptive capacity is most limited, with annual GDP losses of-5.9% by 2100. High-income regions of the Global North, facing milder thermal stress and lower vulnerability, gain about 1.8%. Because the heat penalty falls on outdoor labour, which has no cooling channel, outdoor-intensive economies (India, Sub-Saharan Africa) lose the most. Energy-intensive adaptation partially reverses these losses by an amount that grows with energy use, offsetting 18-40% of GlobalSouth’s loss and flattening the heat-productivity slope by about 29%, but remains bounded by each region’s thermal balance and installed cooling stock. Critically, adaptation response exhibits diminishing returns on additional energy, possibly leading to maladaptation pathways: unconstrained adaptation proves not being cost-effective in most of the cold-relief North and hot but energy-rich Southern economies. Adaptation through energy-intensive cooling solutions is therefore best understood as a targeted instrument with a region-specific optimal level.
