Old Tools, New Ways of Using Them: Harnessing Expert Opinions to Plan for Surprise in Marine Socio-Ecological Systems

Copyright © 2019 Gladstone-Gallagher, Hope, Bulmer, Clark, Stephenson, Mangan, Rullens, Siwicka, Thomas, Pilditch, Savage and Thrush. With globally accelerating rates of environmental disturbance, coastal marine ecosystems are increasingly prone to non-linear regime shifts that result in a loss of ecosystem function and services. A lack of early-detection methods, and an over reliance on limits-based approaches means that these tipping points manifest as surprises. Consequently, marine ecosystems are notoriously difficult to manage, and scientists, managers, and policy makers are paralyzed in a spiral of ecosystem degradation. This paralysis is caused by the inherent need to quantify the risk and uncertainty that surrounds every decision. While progress toward forecasting tipping points is ongoing and important, an interim approach is desperately needed to enable scientists to make recommendations that are credible and defensible in the face of deep uncertainty. We discuss how current tools for developing risk assessments and scenario planning, coupled with expert opinions, can be adapted to bridge gaps in quantitative data, enabling scientists and managers to prepare for many plausible futures. We argue that these tools are currently underutilized in a marine cumulative effects context but offer a way to inform decisions in the interim while predictive models and early warning signals remain imperfect. This approach will require redefining the way we think about managing for ecological surprise to include actions that not only limit drivers of tipping points but increase socio-ecological resilience to yield satisfactory outcomes under multiple possible futures that are inherently uncertain

Identification of a Topological Characteristic Responsible for the Biological Robustness of Regulatory Networks

Attribution of biological robustness to the specific structural properties of a regulatory network is an important yet unsolved problem in systems biology. It is widely believed that the topological characteristics of a biological control network largely determine its dynamic behavior, yet the actual mechanism is still poorly understood. Here, we define a novel structural feature of biological networks, termed ‘regulation entropy’, to quantitatively assess the influence of network topology on the robustness of the systems. Using the cell-cycle control networks of the budding yeast (Saccharomyces cerevisiae) and the fission yeast (Schizosaccharomyces pombe) as examples, we first demonstrate the correlation of this quantity with the dynamic stability of biological control networks, and then we establish a significant association between this quantity and the structural stability of the networks. And we further substantiate the generality of this approach with a broad spectrum of biological and random networks. We conclude that the regulation entropy is an effective order parameter in evaluating the robustness of biological control networks. Our work suggests a novel connection between the topological feature and the dynamic property of biological regulatory networks

The political process of constructing a sustainable London Olympics sports development legacy

This study attempts to develop a research agenda for understanding the process of constructing a sustainable Olympic sports development legacy. The research uses a social constructivist perspective to examine the link between the 2012 London Olympic Games and sustainable sports development. The first part of the paper provides justification for the study of sport policy processes using a constructivist lens. This is followed by a section which critically unpacks sustainable sports development drawing on Mosse’s (1998) ideas of process-oriented research and Searle’s conceptualisation of the construction of social reality. Searle’s (1995) concepts of the assignment of function, collective intentionality, collective rules, and human capacity to cope with the environment are considered in relation to the events and discourses emerging from the legacy vision(s) associated with the 2012 London Olympic Games. The paper concludes by proposing a framework for engaging in process oriented research and highlights key elements, research questions, and methodological issues. The proposed constructivist approach can be used to inform policy, practice, and research on sustainable Olympic sports development legacy

Exploring the Mode of Action of Bioactive Compounds by Microfluidic Transcriptional Profiling in Mycobacteria

10.1371/journal.pone.0069191PLoS ONE87-POLN

Monotone and near-monotone biochemical networks

Monotone subsystems have appealing properties as components of larger networks, since they exhibit robust dynamical stability and predictability of responses to perturbations. This suggests that natural biological systems may have evolved to be, if not monotone, at least close to monotone in the sense of being decomposable into a “small” number of monotone components, In addition, recent research has shown that much insight can be attained from decomposing networks into monotone subsystems and the analysis of the resulting interconnections using tools from control theory. This paper provides an expository introduction to monotone systems and their interconnections, describing the basic concepts and some of the main mathematical results in a largely informal fashion

Runx1 Loss Minimally Impacts Long-Term Hematopoietic Stem Cells

RUNX1 encodes a DNA binding subunit of the core-binding transcription factors and is frequently mutated in acute leukemia, therapy-related leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia. Mutations in RUNX1 are thought to confer upon hematopoietic stem cells (HSCs) a pre-leukemic state, but the fundamental properties of Runx1 deficient pre-leukemic HSCs are not well defined. Here we show that Runx1 deficiency decreases both apoptosis and proliferation, but only minimally impacts the frequency of long term repopulating HSCs (LT-HSCs). It has been variously reported that Runx1 loss increases LT-HSC numbers, decreases LT-HSC numbers, or causes age-related HSC exhaustion. We attempt to resolve these discrepancies by showing that Runx1 deficiency alters the expression of several key HSC markers, and that the number of functional LT-HSCs varies depending on the criteria used to score them. Finally, we identify genes and pathways, including the cell cycle and p53 pathways that are dysregulated in Runx1 deficient HSCs

Does Smoking Status Influence Health-Related Quality of Life Outcome Measures in Patients Undergoing ACDF?

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: Whereas smoking has been shown to affect the fusion rates for patients undergoing an anterior cervical discectomy and fusion (ACDF), the relationship between smoking and health-related quality of life outcome measurements after an ACDF is less clear. The purpose of this study was to evaluate whether smoking negatively affects patient outcomes after an ACDF for cervical degenerative pathology. METHODS: Patients with tumor, trauma, infection, and previous cervical spine surgery and those with less than a year of follow-up were excluded. Smoking status was assessed by self-reported smoking history. Patient outcomes, including Neck Disability Index, Short Form 12 Mental Component Score, Short Form 12 Physical Component Score (PCS-12), Visual Analogue Scale (VAS) arm pain, VAS neck pain, and pseudarthrosis rates were evaluated. Outcomes were compared between smoking groups using multiple linear and logistic regression, controlling for age, sex, and body mass index (BMI), among other factors. A P value \u3c.05 was considered significant. RESULTS: A total of 264 patients were included, with a mean follow-up of 19.8 months, age of 53.1 years, and BMI of 29.6 kg/m2. There were 43 current, 69 former, and 152 nonsmokers in the cohort. At baseline, nonsmokers had higher PCS-12 scores than current smokers (P = .010), lower VAS neck pain than current (P = .035) and former (P = .014) smokers, as well as lower VAS arm pain than former smokers (P = .006). Postoperatively, nonsmokers had higher PCS-12 scores than both current (P = .030) and former smokers (P = .035). Smoking status was not a significant predictor of change in patient outcome in multivariate analysis. CONCLUSIONS: Whereas nonsmokers had higher function and lower pain than former or current smokers preoperatively, smoking status overall was not found to be an independent predictor of outcome scores after ACDF. This supports the notion that smoking status alone should not deter patients from undergoing ACDF for cervical degenerative pathology

IL-10 Blocks the Development of Resistance to Re-Infection with Schistosoma mansoni

Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4+CD44+CD25+GITR+ lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially