Integrating top-down and bottom-up approaches to design global change adaptation at the river basin scale

The high uncertainty associated with the effect of global change on water resource systems calls for a better combination of conventional top-down and bottom-up approaches, in order to design robust adaptation plans at the local scale. The methodological framework presented in this article introduces bottom-up meets top-down integrated approach to support the selection of adaptation measures at the river basin level by comprehensively integrating the goals of economic efficiency, social acceptability, environmental sustainability and adaptation robustness. The top-down approach relies on the use of a chain of models to assess the impact of global change on water resources and its adaptive management over a range of climate projections. Future demand scenarios and locally prioritised adaptation measures are identified following a bottom-up approach through a participatory process with the relevant stakeholders and experts. The optimal combinations of adaptation measures are then selected using a hydro-economic model at basin scale for each climate projection. The resulting adaptation portfolios are, finally, climate checked to define a robust least-regret programme of measures based on trade-offs between adaptation costs and the reliability of supply for agricultural demands. This innovative approach has been applied to a Mediterranean basin, the Orb river basin (France). Mid-term climate projections, downscaled from 9 General Climate Models, are used to assess the uncertainty associated with climate projections. Demand evolution scenarios are developed to project agricultural and urban water demands on the 2030 time horizon. The results derived from the integration of the bottom-up and top-down approaches illustrate the sensitivity of the adaptation strategies to the climate projections, and provide an assessment of the trade-offs between the performance of the water resource system and the cost of the adaptation plan to inform local decision-making. The article contributes new methodological elements for the development of an integrated framework for decision-making under climate change uncertainty, advocating an interdisciplinary approach that bridges the gap between bottom-up and top-down approaches.The study has been financially supported by BRGM-ONEMA joint project on Hydro-economic modelling and by the IMPADAPT project (CGL2013-48424-C2-1-R) from the Spanish ministry MINECO (Ministerio de Economia y Competitividad) with European FEDER funds. Corentin Girard is supported by a grant from the University Lecturer Training Program (FPU12/03803) of the Ministry of Education, Culture and Sports of Spain. We also acknowledge the CERFACS for the climate scenarios provided from the SCRATCH 2010 dataset (March 2012 release - http://www.cerfacs.fr/similar to page/work/scratch/). We thank as well the anonymous reviewers and the Editors of Global Environmental Change, for their useful and encouraging comments during the review process.Girard, CDP.; Pulido-Velazquez, M.; Rinaudo, J.; Page Oliva, C.; Caballero, I. (2015). Integrating top-down and bottom-up approaches to design global change adaptation at the river basin scale. Global Environmental Change. 34:132-146. https://doi.org/10.1016/j.gloenvcha.2015.07.002S1321463

Genome-wide DNA methylation in saliva and body size of adolescent girls

Aim: We performed an epigenome-wide association study within the Finnish Health in Teens cohort to identify differential DNA methylation and its association with BMI in adolescents. Materials & methods: Differential DNA methylation analyses of 3.1 million CpG sites were performed in saliva samples from 50 lean and 50 heavy adolescent girls by genome-wide targeted bisulfite-sequencing. Results: We identified 100 CpG sites with p-values <0.000524, seven regions by 'bumphunting' and five CpG islands that differed significantly between the two groups. The ten CpG sites and regions most strongly associated with BMI substantially overlapped with obesity-and insulin-related genes, including MC2R, IGFBPL1, IP6K1 and IGF2BP1. Conclusion: Our findings suggest an association between the saliva methylome and BMI in adolescence.Peer reviewe

Epigenetics, heritability and longitudinal analysis

Background Longitudinal data and repeated measurements in epigenome-wide association studies (EWAS) provide a rich resource for understanding epigenetics. We summarize 7 analytical approaches to the GAW20 data sets that addressed challenges and potential applications of phenotypic and epigenetic data. All contributions used the GAW20 real data set and employed either linear mixed effect (LME) models or marginal models through generalized estimating equations (GEE). These contributions were subdivided into 3 categories: (a) quality control (QC) methods for DNA methylation data; (b) heritability estimates pretreatment and posttreatment with fenofibrate; and (c) impact of drug response pretreatment and posttreatment with fenofibrate on DNA methylation and blood lipids. Results Two contributions addressed QC and identified large statistical differences with pretreatment and posttreatment DNA methylation, possibly a result of batch effects. Two contributions compared epigenome-wide heritability estimates pretreatment and posttreatment, with one employing a Bayesian LME and the other using a variance-component LME. Density curves comparing these studies indicated these heritability estimates were similar. Another contribution used a variance-component LME to depict the proportion of heritability resulting from a genetic and shared environment. By including environmental exposures as random effects, the authors found heritability estimates became more stable but not significantly different. Two contributions investigated treatment response. One estimated drug-associated methylation effects on triglyceride levels as the response, and identified 11 significant cytosine-phosphate-guanine (CpG) sites with or without adjusting for high-density lipoprotein. The second contribution performed weighted gene coexpression network analysis and identified 6 significant modules of at least 30 CpG sites, including 3 modules with topological differences pretreatment and posttreatment. Conclusions Four conclusions from this GAW20 working group are: (a) QC measures are an important consideration for EWAS studies that are investigating multiple time points or repeated measurements; (b) application of heritability estimates between time points for individual CpG sites is a useful QC measure for DNA methylation studies; (c) drug intervention demonstrated strong epigenome-wide DNA methylation patterns across the 2 time points; and (d) new statistical methods are required to account for the environmental contributions of DNA methylation across time. These contributions demonstrate numerous opportunities exist for the analysis of longitudinal data in future epigenetic studies

Comprehensible Control for Researchers and Developers facing Data Challenges

The DARE platform enables researchers and their developers to exploit more capabilities to handle complexity and scale in data, computation and collaboration. Today’s challenges pose increasing and urgent demands for this combination of capabilities. To meet technical, economic and governance constraints, application communities must use use shared digital infrastructure principally via virtualisation and mapping. This requires precise abstractions that retain their meaning while their implementations and infrastructures change. Giving specialists direct control over these capabilities with detail relevant to each discipline is necessary for adoption. Research agility, improved power and retained return on intellectual investment incentivise that adoption. We report on an architecture for establishing and sustaining the necessary optimised mappings and early evaluations of its feasibility with two application communities.PublishedSan Diego (CA, USA)3IT. Calcolo scientific

Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study.

Funder: Folkehelseinstituttet/Norwegian Institute of Public HealthFunder: Norwegian Ministry of Health and Care ServicesFunder: Norwegian Ministry of Health and Care Services and the Norwegian Ministry of Education and ResearchFunder: Norwegian Ministry of Education and ResearchStudy questionWhat is the association between BMI and subfertility?Summary answerWe observed a J-shaped relationship between BMI and subfertility in both sexes, when using both a standard multivariable regression and Mendelian randomization (MR) analysis.What is known alreadyHigh BMI in both women and men is associated with subfertility in observational studies and this relationship is further substantiated by a few small randomized controlled trials of weight reduction and success of assisted reproduction. Women with low BMI also have lower conception rates with assisted reproduction technologies.Study design, size, durationCohort study (the Norwegian Mother, Father and Child Cohort Study), 28 341 women and 26 252 men, recruited from all over Norway between 1999 and 2008.Participants/materials, setting, methodsWomen (average age 30, average BMI 23.1 kg/m2) and men (average age 33, average BMI 25.5 kg/m2) had available genotype data and provided self-reported information on time-to-pregnancy and BMI. A total of 10% of couples were subfertile (time-to-pregnancy ≥12 months).Main results and the role of chanceOur findings support a J-shaped association between BMI and subfertility in both sexes using multivariable logistic regression models. Non-linear MR validated this relationship. A 1 kg/m2 greater genetically predicted BMI was linked to 18% greater odds of subfertility (95% CI 5% to 31%) in obese women (≥30.0 kg/m2) and 15% lower odds of subfertility (-24% to -2%) in women with BMI Limitations, reasons for cautionThe main limitations of our study were that we did not know whether the subfertility was driven by the women, men or both; the exclusive consideration of individuals of northern European ancestry; and the limited amount of participants with obesity or BMI values Wider implications of the findingsOur results support a causal effect of obesity on subfertility in women and men. Our findings also expand the current evidence by indicating that individuals with BMI values Study funding/competing interest(s)The MoBa Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Norwegian Ministry of Education and Research. This project received funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement No 947684). It was also partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. Open Access funding was provided by the Folkehelseinstituttet/Norwegian Institute of Public Health. D.A.L. is a UK National Institute for Health Research Senior Investigator (NF-SI-0611-10196) and is supported by the US National Institutes of Health (R01 DK10324) and a European Research Council Advanced Grant (DevelopObese; 669545). The funders had no role in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. D.A.L. receives (or has received in the last 10 years) research support from National and International government and charitable bodies, Roche Diagnostics and Medtronic for research unrelated to the current work. The rest of the authors declare that no competing interests exist.Trial registration numberN/A

Effectiveness of a structured, framework-based approach to implementation: the Researching Effective Approaches to Cleaning in Hospitals (REACH) Trial

BACKGROUND: Implementing sustainable practice change in hospital cleaning has proven to be an ongoing challenge in reducing healthcare associated infections. The purpose of this study was to develop a reliable framework-based approach to implement and quantitatively evaluate the implementation of evidence-based practice change in hospital cleaning. DESIGN/METHODS: The Researching Effective Approaches to Cleaning in Hospitals (REACH) trial was a pragmatic, stepped-wedge randomised trial of an environmental cleaning bundle implemented in 11 Australian hospitals from 2016 to 2017. Using a structured multi-step approach, we adapted the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to support rigorous and tailored implementation of the cleaning bundle intervention in eleven diverse and complex settings. To evaluate the effectiveness of this strategy we examined post-intervention cleaning bundle alignment calculated as a score (an implementation measure) and cleaning performance audit data collected using ultraviolet (UV) gel markers (an outcome measure). RESULTS: We successfully implemented the bundle and observed improvements in cleaning practice and performance, regardless of hospital size, intervention duration and contextual issues such as staff and organisational readiness at baseline. There was a positive association between bundle alignment scores and cleaning performance at baseline. This diminished over the duration of the intervention, as hospitals with lower baseline scores were able to implement practice change successfully. CONCLUSION: Using a structured framework-based approach allows for pragmatic and successful implementation of clinical trials across diverse settings, and assists with quantitative evaluation of practice change. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12615000325505, registered on 4 September 2015

The Topological B-model on a Mini-Supertwistor Space and Supersymmetric Bogomolny Monopole Equations

In the recent paper hep-th/0502076, it was argued that the open topological B-model whose target space is a complex (2|4)-dimensional mini-supertwistor space with D3- and D1-branes added corresponds to a super Yang-Mills theory in three dimensions. Without the D1-branes, this topological B-model is equivalent to a dimensionally reduced holomorphic Chern-Simons theory. Identifying the latter with a holomorphic BF-type theory, we describe a twistor correspondence between this theory and a supersymmetric Bogomolny model on R^3. The connecting link in this correspondence is a partially holomorphic Chern-Simons theory on a Cauchy-Riemann supermanifold which is a real one-dimensional fibration over the mini-supertwistor space. Along the way of proving this twistor correspondence, we review the necessary basic geometric notions and construct action functionals for the involved theories. Furthermore, we discuss the geometric aspect of a recently proposed deformation of the mini-supertwistor space, which gives rise to mass terms in the supersymmetric Bogomolny equations. Eventually, we present solution generating techniques based on the developed twistorial description together with some examples and comment briefly on a twistor correspondence for super Yang-Mills theory in three dimensions.Comment: 55 pages; v2: typos fixed, published versio