Causal attribution fractions, and the attribution of smoking and BMI to the landscape of disease incidence in UK Biobank.

Unlike conventional epidemiological studies that use observational data to estimate "associations" between risk factors and disease, the science of causal inference has identified situations where causal estimates can be made from observational data, using results such as the "backdoor criteria". Here these results are combined with established epidemiological methods, to calculate simple population attribution fractions that estimate the causal influence of risk factors on disease incidence, and can be estimated using conventional proportional hazards methods. A counterfactual argument gives an attribution fraction for individuals. Causally meaningful attribution fractions cannot be constructed for all risk factors or confounders, but they can for the important established risk factors of smoking and body mass index (BMI). Using the new results, the causal attribution of smoking and BMI to the incidence of 226 diseases in the UK Biobank are estimated, and summarised in terms of disease chapters from the International Classification of Diseases (ICD-10). The diseases most strongly attributed to smoking and BMI are identified, finding 11 with attribution fractions greater than 0.5, and a small number with protective associations. The results provide new tools to quantify the causal influence of risk factors such as smoking and BMI on disease, and survey the causal influence of smoking and BMI on the landscape of disease incidence in the UK Biobank population.

Sporadic, late-onset, and multistage diseases.

Multistage disease processes are often characterized by a linear relationship between the log of incidence rates and the log of age. Examples include sequences of somatic mutations, that can cause cancer, and have recently been linked with a range of non-malignant diseases. Using a Weibull distribution to model diseases that occur through an ordered sequence of stages, and another model where stages can occur in any order, we characterized the age-related onset of disease in UK Biobank data. Despite their different underlying assumptions, both models accurately described the incidence of over 450 diseases, demonstrating that multistage disease processes cannot be inferred from this data alone. The parametric models provided unique insights into age-related disease, that conventional studies of relative risks cannot. The rate at which disease risk increases with age was used to distinguish between "sporadic" diseases, with an initially low and slowly increasing risk, and "late-onset" diseases whose negligible risk when young rapidly increases with age. "Relative aging rates" were introduced to quantify how risk factors modify age-related risk, finding the effective age-at-risk of sporadic diseases is strongly modified by common risk factors. Relative aging rates are ideal for risk-stratification, allowing the identification of ages with equivalent-risk in groups with different exposures. Most importantly, our results suggest that a substantial burden of sporadic diseases can be substantially delayed or avoided by early lifestyle interventions.

The changing face of science communication, technology, extension and improved decision-making at the farm-water quality interface.

In recent decades, significant advances have been made in understanding the generation, fates and consequences of water quality pollutants in the Great Barrier Reef ecosystem. However, skepticism and lack of trust in water quality science by farming stakeholders has emerged as a significant challenge. The ongoing failures of both compulsory and particularly voluntary practices to improve land management and reduce diffuse agricultural pollution from the Great Barrier Reef catchment underlines the need for more effective communication of water quality issues at appropriate decision-making scales to landholders. Using recent Great Barrier Reef catchment experiences as examples, we highlight several emerging themes and opportunities in using technology to better communicate land use-water quality impacts and delivery of actionable knowledge to farmers, specifically supporting decision-making, behavior change, and the spatial identification of nutrient generation 'hotspots' in intensive agriculture catchments. We also make recommendations for co-designed monitoring-extension platforms involving farmers, governments, researchers, and related agencies, to cut across stakeholder skepticism, and achieve desired water quality and ecosystem outcomes.

Grasping at digitalisation: turning imagination into fact in the sugarcane farming community.

Nutrient runoff from catchments that drain into the Great Barrier Reef (GBR) is a significant source of stress for this World Heritage Area. An alliance of collaborative on-ground water quality monitoring (Project 25) and technologically driven digital application development (Digiscape GBR) projects were formulated to provide data that highlighted the contribution of a network of Australian sugar cane farmers, amongst other sources, to nutrient runoff. This environmental data and subsequent information were extended to the farming community through scientist-led feedback sessions and the development of specialised digital technology (1622™WQ) that help build an understanding of the nutrient movements, in this case nitrogen, such that farmers might think about and eventually act to alter their fertilizer application practices. This paper reflects on a socio-environmental sustainability challenge that emerged during this case study, by utilising the nascent concept of digi-grasping. We highlight the importance of the entire agricultural knowledge and advice network being part of an innovation journey to increase the utility of digital agricultural technologies developed to increase overall sustainability. We develop the digi-MAST analytical framework, which explores modes of being and doing in the digital world, ranging from 'the everyday mystery of the digital world (M)', through digital 'awareness (A)', digitally 'sparked' being/s (S), and finally the ability of individuals and/or groups to 'transform (T)' utilising digital technologies and human imaginations. Our digi-MAST framework allows us to compare agricultural actors, in this case, to understand present modes of digi-grasping to help determine the resources and actions likely to be required to achieve impact from the development of various forms of digital technological research outputs.

Multi-stage models for the failure of complex systems, cascading disasters, and the onset of disease.

Complex systems can fail through different routes, often progressing through a series of (rate-limiting) steps and modified by environmental exposures. The onset of disease, cancer in particular, is no different. Multi-stage models provide a simple but very general mathematical framework for studying the failure of complex systems, or equivalently, the onset of disease. They include the Armitage-Doll multi-stage cancer model as a particular case, and have potential to provide new insights into how failures and disease, arise and progress. A method described by E.T. Jaynes is developed to provide an analytical solution for a large class of these models, and highlights connections between the convolution of Laplace transforms, sums of random variables, and Schwinger/Feynman parameterisations. Examples include: exact solutions to the Armitage-Doll model, the sum of Gamma-distributed variables with integer-valued shape parameters, a clonal-growth cancer model, and a model for cascading disasters. Applications and limitations of the approach are discussed in the context of recent cancer research. The model is sufficiently general to be used in many contexts, such as engineering, project management, disease progression, and disaster risk for example, allowing the estimation of failure rates in complex systems and projects. The intended result is a mathematical toolkit for applying multi-stage models to the study of failure rates in complex systems and to the onset of disease, cancer in particular.