Predictive abilities comparison from multiple dynamic prediction models.

With the development of personalized medicine, the study of individual prognosis appears to be a major contemporary scientific issue. Dynamic models are particularly well adapted to such studies by allowing some potential changes in the follow-up to be taken into account. In particular, this leads to more accurate predictions by updating the available information throughout the patient monitoring. Some mathematical tools have been developed to quantify and compare the effectiveness of dynamic predictions using dynamic versions of the area under the receiver operating characteristic curve and the Brier score in the competing risks setting. Nevertheless, only two predictive abilities can be compared. This may be too restrictive in a clinical context where more and more information can be collected during patient follow-up thanks to recent technological advances. Here we propose a new procedure that allows multiple comparisons of the predictive abilities of different biomarkers, based on the dynamic area under the receiver operating characteristic curve or Brier score. Performances of our testing procedure were assessed by simulations. Moreover, a motivating application in hepatology will be presented. Finally, this work compares more than two dynamic predictive abilities of biomarkers and is available via R functions on GitHub.

Dynamic personalized prediction of the individual liver-related risk after sustained viral response in HCV patients.

Sustained viral response (SVR) significantly improves the prognosis in patients with hepatitis C virus (HCV) chronic infection but does not totally alleviate the risk of liver-related complications (LRC). We aimed to evaluate whether the dynamics of multiple measurements of simple parameters after SVR enable the development of a personalized prediction of prognosis in HCV patients. HCV mono-infected patients who experienced SVR in two prospective cohorts (ANRS CO12 CirVir cohort: derivation set; ANRS CO22 HEPATHER cohort: validation set) were included. The study outcome was LRC, a composite criterion including decompensation of cirrhosis and/or hepatocellular carcinoma. Joint latent class modelling accounting for both biomarker trajectory and event occurrence during follow-up was developed in the derivation set to compute individual dynamic predictions, with further evaluation in the validation set. In the derivation set (n = 695; 50 LRC during the median 3.8 [1.6-7.5] years follow-up), FIB4 was identified as a biomarker associated with LRC occurrence after SVR. Joint modelling used sex and the dynamics of FIB4 and diabetes status to develop a personalized prediction of LRC. In the validation set (n = 7064; 273 LRC during the median 3.6 [2.5-4.9] years follow-up), individual dynamic predictions from the model accurately stratified the risk of LRC. Time-dependent Brier Score showed good calibration that improved with the accumulation of visits, justifying our modelling approach considering both baseline and follow-up measurements. Dynamic modelling using repeated measurements of simple parameters predicts the individual residual risk of LRC and improves personalized medicine after SVR in HCV patients.

Nature-based solutions (NbS): A management paradigm shift in practitioners' perspectives on riverbank soil bioengineering.

Nature-based Solutions (NbS) are promoted as practical and theoretical solutions that simultaneously provide human well-being and biodiversity benefits. One example is soil bioengineering using construction techniques based on living vegetation, and is frequently used for riverbank stabilization, flood protection, and erosion control. Compared with civil engineering, NbS offer many advantages such as cost reduction, limited impact on the environment, and production of ecosystem services. However, their use is still marginal for riverbank control, especially in urban areas. In this paper, we focus on soil bioengineering techniques for riverbank protection in an urban context from the practitioners' perspective. We question to what extent NbS require a shift in management paradigm. We used qualitative methods to interview 17 practitioners working in the Rhone Alps basin (France). Our results reveal that switching from civil engineering to soil bioengineering is not only a technical change, but also requires a shift from a "predict and control" paradigm to an "adaptive management" paradigm because of three major reasons. First, soil bioengineering techniques require redefinition of the performance of engineering structures with the inclusion of ecological and social dimensions. Second, the adoption of soil bioengineering techniques requires that practitioners, elected people and inhabitants reconsider risk sharing and acceptance. Third, the techniques require practitioners to adopt a new posture, with new soft skills (humility and daring) and a new collective organization (collective feedback). Finally, we identify three levers for a broader use of such techniques: (i) systematic assessment of the ecological, economical, and social benefits of such techniques; (ii) improving risk acceptance and sharing; (iii) fostering of social learning among practitioners through collective or technical feedback.

Non-invasive tests accurately stratify patients with NAFLD based on their risk of liver-related events.

BACKGROUND & AIMS: Previous studies on the prognostic significance of non-invasive liver fibrosis tests in non-alcoholic fatty liver disease (NAFLD) lack direct comparison to liver biopsy. We aimed to evaluate the prognostic accuracy of fibrosis-4 (FIB4) and vibration-controlled transient elastography (VCTE), compared to liver biopsy, for the prediction of liver-related events (LREs) in NAFLD. METHODS: A total of 1,057 patients with NAFLD and baseline FIB4 and VCTE were included in a multicenter cohort. Of these patients, 594 also had a baseline liver biopsy. The main study outcome during follow-up was occurrence of LREs, a composite endpoint combining cirrhosis complications and/or hepatocellular carcinoma. Discriminative ability was evaluated using Harrell's C-index. RESULTS: FIB4 and VCTE showed good accuracy for the prediction of LREs, with Harrell's C-indexes >0.80 (0.817 [0.768-0.866] vs. 0.878 [0.835-0.921], respectively, p = 0.059). In the biopsy subgroup, Harrell's C-indexes of histological fibrosis staging and VCTE were not significantly different (0.932 [0.910-0.955] vs. 0.881 [0.832-0.931], respectively, p = 0.164), while both significantly outperformed FIB4 for the prediction of LREs. FIB4 and VCTE were independent predictors of LREs in the whole study cohort. The stepwise FIB4-VCTE algorithm accurately stratified the risk of LREs: compared to patients with "FIB4 <1.30", those with "FIB4 ≥1.30 then VCTE <8.0 kPa" had similar risk of LREs (adjusted hazard ratio [aHR] 1.3; 95% CI 0.3-6.8), whereas the risk of LREs significantly increased in patients with "FIB4 ≥1.30 then VCTE 8.0-12.0 kPa" (aHR 3.8; 95% CI 1.3-10.9), and even more for those with "FIB4 ≥1.30 then VCTE >12.0 kPa" (aHR 12.4; 95% CI 5.1-30.2). CONCLUSION: VCTE and FIB4 accurately stratify patients with NAFLD based on their risk of LREs. These non-invasive tests are alternatives to liver biopsy for the identification of patients in need of specialized management. LAY SUMMARY: The amount of fibrosis in the liver is closely associated with the risk of liver-related complications in non-alcoholic fatty liver disease (NAFLD). Liver biopsy currently remains the reference standard for the evaluation of fibrosis, but its application is limited by its invasiveness. Therefore, we evaluated the ability of non-invasive liver fibrosis tests to predict liver-related complications in NAFLD. Our results show that the blood test FIB4 and transient elastography stratify the risk of liver-related complications in NAFLD, and that transient elastography has similar prognostic accuracy as liver biopsy. These results support the use of non-invasive liver fibrosis tests instead of liver biopsy for the management of patients with NAFLD.

Game of Cruxes: co-designing a game for scientists and stakeholders for identifying joint problems.

Scientists increasingly cross their disciplinary boundaries and connect with local stakeholders to jointly solve complex problems. Working with stakeholders means higher legitimacy and supports practical impact of research. Games provide a tool to achieve such transdisciplinary collaboration. In this paper, we explore the use of a game in a participatory project where scientists and local stakeholders are seeking and defining a joint problem. The literature is clear that this step is essential but remains short on concrete methods. Here, we explore this potential in practice. We conducted parallel participatory processes in two alpine regions considered as socio-ecological system (SES) in Switzerland and France, both vulnerable to global change. Based on these two case studies, we co-constructed a game, integrating scientific concerns about key land use, climate change and socio-economic elements of a mountain SES (tourism, agriculture, housing and demography). With the game, we assessed the existence of joint problems connecting scientific and local interests. The game successfully engaged participants at both sites over 11 game sessions, showing potential of use in other transdisciplinary settings. By covering a wide array of issues, the game created a discussion space for listing problems and identifying where scientist and stakeholder interests overlap. In Switzerland, the game revealed no pressing joint problem to be addressed. In France, game sessions revealed, among other problems, an enduring and complex issue regarding the co-existence of inhabitants and powerful institutions. Having demonstrated the capacity of this game for joint-problem assessment, we believe other participatory research in similar SES could benefit from an early use of such an approach to frame the potential for collaboration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11625-021-00983-2.

Exploring the future of land use and food security: A new set of global scenarios.

Facing a growing and more affluent world population, changing climate and finite natural resources, world food systems will have to change in the future. The aim of the Agrimonde-Terra foresight study was to build global scenarios linking land use and food security, with special attention paid to overlooked aspects such as nutrition and health, in order to help explore the possible future of the global food system. In this article, we seek to highlight how the resulting set of scenarios contributes to the debate on land use and food security and enlarges the range of possible futures for the global food system. We highlight four main contributions. Combining a scenario building method based on morphological analysis and quantitative simulations with a tractable and simple biomass balance model, the proposed approach improves transparency and coherence between scenario narratives and quantitative assessment. Agrimonde-Terra's scenarios comprise a wide range of alternative diets, with contrasting underlying nutritional and health issues, which accompany contrasting urbanization and rural transformation processes, both dimensions that are lacking in other sets of global scenarios. Agrimonde-Terra's scenarios share some similarities with existing sets of global scenarios, notably the SSPs, but are usually less optimistic regarding agricultural land expansion up to 2050. Results suggest that changing global diets toward healthier patterns could also help to limit the expansion in agricultural land area. Agrimonde-Terra's scenarios enlarge the scope of possible futures by proposing two pathways that are uncommon in other sets of global scenarios. The first proposes to explore possible reconnection of the food industry and regional production within supranational regional blocs. The second means that we should consider that a 'perfect storm', induced by climate change and an ecological crisis combined with social and economic crises, is still possible. Both scenarios should be part of the debate as the current context of the COVID-19 pandemic shows.