A typology of community and stakeholder engagement based on documented examples in the field of novel vector control.

BackgroundDespite broad consensus on the importance of community and stakeholder engagement (CSE) for guiding the development, regulation, field testing, and deployment of emerging vector control technologies (such as genetically engineered insects), the types of activities pursued have varied widely, as have the outcomes. We looked to previous CSE efforts for clarity about appropriate methods and goals. Our analysis yielded a typology of CSE, and related vocabulary, that describes distinctions that funders, organizers, and scholars should make when proposing or evaluating CSE.MethodsWe compiled available formal documentation of CSE projects, starting with projects mentioned in interviews with 17 key informants. Major features of these examples, including the initiators, target groups, timing, goals, and methods were identified using qualitative coding. Based on these examples, subcategories were developed for a subset of features and applied to the identified cases of CSE in the documents. Co-occurrence of subcategorized features was examined for patterns.ResultsWe identified 14 documented examples CSE projects, which were comprised of 28 distinct CSE activities. We found no clear patterns with respect to timing. However, we found that grouping examples according to whether initiators or targets could enact the immediate desired outcome could help to clarify relationships between goals, methods, and targets.ConclusionBased on this analysis, we propose a typology that distinguishes three categories of CSE: engagement to inquire -where initiators are empowered to act on information collected through engagement with target groups; engagement to influence -where initiators engage to affect the actions of already-empowered target groups; and engagement to involve -where initiators engage to delegate authority to target groups. The proposed typology can serve as a guide for establishing the goals, identifying appropriate methods, and evaluating and reporting CSE projects by directing attention to important questions to be asked well before determining who to engage and how

A Path to Implement Precision Child Health Cardiovascular Medicine.

Congenital heart defects (CHDs) affect approximately 1% of live births and are a major source of childhood morbidity and mortality even in countries with advanced healthcare systems. Along with phenotypic heterogeneity, the underlying etiology of CHDs is multifactorial, involving genetic, epigenetic, and/or environmental contributors. Clear dissection of the underlying mechanism is a powerful step to establish individualized therapies. However, the majority of CHDs are yet to be clearly diagnosed for the underlying genetic and environmental factors, and even less with effective therapies. Although the survival rate for CHDs is steadily improving, there is still a significant unmet need for refining diagnostic precision and establishing targeted therapies to optimize life quality and to minimize future complications. In particular, proper identification of disease associated genetic variants in humans has been challenging, and this greatly impedes our ability to delineate gene-environment interactions that contribute to the pathogenesis of CHDs. Implementing a systematic multileveled approach can establish a continuum from phenotypic characterization in the clinic to molecular dissection using combined next-generation sequencing platforms and validation studies in suitable models at the bench. Key elements necessary to advance the field are: first, proper delineation of the phenotypic spectrum of CHDs; second, defining the molecular genotype/phenotype by combining whole-exome sequencing and transcriptome analysis; third, integration of phenotypic, genotypic, and molecular datasets to identify molecular network contributing to CHDs; fourth, generation of relevant disease models and multileveled experimental investigations. In order to achieve all these goals, access to high-quality biological specimens from well-defined patient cohorts is a crucial step. Therefore, establishing a CHD BioCore is an essential infrastructure and a critical step on the path toward precision child health cardiovascular medicine

Gene Regulatory Networks: Modeling, Intervention and Context

abstract: Biological systems are complex in many dimensions as endless transportation and communication networks all function simultaneously. Our ability to intervene within both healthy and diseased systems is tied directly to our ability to understand and model core functionality. The progress in increasingly accurate and thorough high-throughput measurement technologies has provided a deluge of data from which we may attempt to infer a representation of the true genetic regulatory system. A gene regulatory network model, if accurate enough, may allow us to perform hypothesis testing in the form of computational experiments. Of great importance to modeling accuracy is the acknowledgment of biological contexts within the models -- i.e. recognizing the heterogeneous nature of the true biological system and the data it generates. This marriage of engineering, mathematics and computer science with systems biology creates a cycle of progress between computer simulation and lab experimentation, rapidly translating interventions and treatments for patients from the bench to the bedside. This dissertation will first discuss the landscape for modeling the biological system, explore the identification of targets for intervention in Boolean network models of biological interactions, and explore context specificity both in new graphical depictions of models embodying context-specific genomic regulation and in novel analysis approaches designed to reveal embedded contextual information. Overall, the dissertation will explore a spectrum of biological modeling with a goal towards therapeutic intervention, with both formal and informal notions of biological context, in such a way that will enable future work to have an even greater impact in terms of direct patient benefit on an individualized level.Dissertation/ThesisPh.D. Computer Science 201

Systems approaches and algorithms for discovery of combinatorial therapies

Effective therapy of complex diseases requires control of highly non-linear complex networks that remain incompletely characterized. In particular, drug intervention can be seen as control of signaling in cellular networks. Identification of control parameters presents an extreme challenge due to the combinatorial explosion of control possibilities in combination therapy and to the incomplete knowledge of the systems biology of cells. In this review paper we describe the main current and proposed approaches to the design of combinatorial therapies, including the empirical methods used now by clinicians and alternative approaches suggested recently by several authors. New approaches for designing combinations arising from systems biology are described. We discuss in special detail the design of algorithms that identify optimal control parameters in cellular networks based on a quantitative characterization of control landscapes, maximizing utilization of incomplete knowledge of the state and structure of intracellular networks. The use of new technology for high-throughput measurements is key to these new approaches to combination therapy and essential for the characterization of control landscapes and implementation of the algorithms. Combinatorial optimization in medical therapy is also compared with the combinatorial optimization of engineering and materials science and similarities and differences are delineated.Comment: 25 page

Food security, risk management and climate change

This report identifies major constraints to the adaptive capacity of food organisations operating in Australia. This report is about food security, climate change and risk management. Australia has enjoyed an unprecedented level of food security for more than half a century, but there are new uncertainties emerging and it would be unrealistic – if not complacent – to assume the same level of food security will persist simply because of recent history. The project collected data from more than 36 case study organisations (both foreign and local) operating in the Australian food-supply chain, and found that for many businesses,  risk management practices require substantial improvement to cope with and exploit the uncertainties that lie ahead. Three risks were identified as major constraints to adaptive capacity of food organisations operating in Australia:  risk management practices; an uncertain regulatory environment – itself a result of gaps in risk management; climate change uncertainty and projections about climate change impacts, also related to risk management

Global Risks 2015, 10th Edition.

The 2015 edition of the Global Risks report completes a decade of highlighting the most significant long-term risks worldwide, drawing on the perspectives of experts and global decision-makers. Over that time, analysis has moved from risk identification to thinking through risk interconnections and the potentially cascading effects that result. Taking this effort one step further, this year's report underscores potential causes as well as solutions to global risks. Not only do we set out a view on 28 global risks in the report's traditional categories (economic, environmental, societal, geopolitical and technological) but also we consider the drivers of those risks in the form of 13 trends. In addition, we have selected initiatives for addressing significant challenges, which we hope will inspire collaboration among business, government and civil society communitie

Microbiota and chronic inflammatory arthritis. an interwoven link

Background: Only recently, the scientific community gained insights on the importance of the intestinal resident flora for the host's health and disease. Gut microbiota in fact plays a crucial role in modulating innate and acquired immune responses and thus interferes with the fragile balance inflammation versus tolerance. Main body: Correlations between gut bacteria composition and the severity of inflammation have been studied in inflammatory bowel diseases. More recently similar alterations in the gut microbiota have been reported in patients with spondyloarthritis, whereas in rheumatoid arthritis an accumulating body of evidence evokes a pathogenic role for the altered oral microbiota in disease development and course. In the context of dysbiosis it is also important to remember that different environmental factors like stress, smoke and dietary components can induce strong bacterial changes and consequent exposure of the intestinal epithelium to a variety of different metabolites, many of which have an unknown function. In this perspective, and in complex disorders like autoimmune diseases, not only the genetic makeup, sex and immunologic context of the individual but also the structure of his microbial community should be taken into account. Conclusions: Here we provide a review of the role of the microbiota in the onset, severity and progression of chronic inflammatory arthritis as well as its impact on the therapeutic management of these patients. Furthermore we point-out the complex interwoven link between gut-joint-brain and immune system by reviewing the most recent data on the literature on the importance of environmental factors such as diet, smoke and stress