Detection of bifurcations in noisy coupled systems from multiple time series

This is the final version of the article. Available from AIP Publishing via the DOI in this record.We generalize a method of detecting an approaching bifurcation in a time series of a noisy system from the special case of one dynamical variable to multiple dynamical variables. For a system described by a stochastic differential equation consisting of an autonomous deterministic part with one dynamical variable and an additive white noise term, small perturbations away from the system's fixed point will decay slower the closer the system is to a bifurcation. This phenomenon is known as critical slowing down and all such systems exhibit this decay-type behaviour. However, when the deterministic part has multiple coupled dynamical variables, the possible dynamics can be much richer, exhibiting oscillatory and chaotic behaviour. In our generalization to the multi-variable case, we find additional indicators to decay rate, such as frequency of oscillation. In the case of approaching a homoclinic bifurcation, there is no change in decay rate but there is a decrease in frequency of oscillations. The expanded method therefore adds extra tools to help detect and classify approaching bifurcations given multiple time series, where the underlying dynamics are not fully known. Our generalisation also allows bifurcation detection to be applied spatially if one treats each spatial location as a new dynamical variable. One may then determine the unstable spatial mode(s). This is also something that has not been possible with the single variable method. The method is applicable to any set of time series regardless of its origin, but may be particularly useful when anticipating abrupt changes in the multi-dimensional climate system.The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under Grant Agreement No. 603864 (HELIX). We thank Jan Sieber for help in identifying the case studies and useful comments on an early draft of the manuscript

Boston type 1 keratoprosthesis from patient selection through postoperative management: a review for the keratoprosthetic surgeon

Samantha L Williamson,1 M Soledad Cortina2 1Department of Ophthalmology, Kaiser Permanente Mid-Atlantic Medical Group, Baltimore, MD, USA; 2Department of Ophthalmology and Visual Sciences, University of Illinois Eye and Ear Infirmary, Chicago, IL, USA Abstract: For the anterior segment surgeon, the implantation of Boston type 1 keratoprosthesis is a multistep process that begins with careful patient selection. Success depends on thorough preoperative evaluation, detailed surgical planning, and frequent postoperative follow-up. New practice patterns have emerged for each of these phases as the international experience with keratoprosthesis grows. This review details special considerations that can improve outcomes and also allow surgeons to consider its use in challenging patient populations at each step. Keywords: Keratoprosthesis, aniridia, ocular cicatricial pemphigoid, Stevens–Johnson syndrom

Theoretical foundations of emergent constraints: relationships between climate sensitivity and global temperature variability in conceptual models

This is the final version. Available on open access from OUP via the DOI in this recordBackground: The emergent constraint approach has received interest recently as a way of utilizing multimodel General Circulation Model (GCM) ensembles to identify relationships between observable variations of climate and future projections of climate change. These relationships, in combination with observations of the real climate system, can be used to infer an emergent constraint on the strength of that future projection in the real system. However, there is as yet no theoretical framework to guide the search for emergent constraints. As a result, there are significant risks that indiscriminate data-mining of the multidimensional outputs from GCMs could lead to spurious correlations and less than robust constraints on future changes. To mitigate against this risk, Cox et al (hereafter CHW18) proposed a theory-motivated emergent constraint, using the one-box Hasselmann model to identify a linear relationship between equilibrium climate sensitivity (ECS) and a metric of global temperature variability involving both temperature standard deviation and autocorrelation (Ψ). A number of doubts have been raised about this approach, some concerning the application of the one-box model to understand relationships in complex GCMs which are known to have more than the single characteristic timescale. Objectives: To study whether the linear Ψ-ECS proportionality in CHW18 is an artefact of the one-box model. More precisely we ask ‘Does the linear Ψ-ECS relationship feature in the more complex and realistic two-box and diffusion models?’. Methods: We solve the two-box and diffusion models to find relationships between ECS and Ψ. These models are forced continually with white noise parameterizing internal variability. The resulting analytical relations are essentially fluctuation-dissipation theorems. Results: We show that the linear Ψ-ECS proportionality in the one-box model is not generally true in the two-box and diffusion models. However, the linear proportionality is a very good approximation for parameter ranges applicable to the current state-of-the-art CMIP5 climate models. This is not obvious - due to structural differences between the conceptual models, their predictions also differ. For example, the two-box and diffusion, unlike the one-box model, can reproduce the long term transient behaviour of the CMIP5 abrupt4xCO2 and 1pcCO2 simulations. Each of the conceptual models also predict different power spectra with only the diffusion model’s pink 1/f spectrum being compatible with observations and GCMs. We also show that the theoretically predicted Ψ-ECS relationship exists in the piControl as well as historical CMIP5 experiments and that the differing gradients of the proportionality are inversely related to the effective forcing in that experiment. Conclusions: We argue that emergent constraints should ideally be derived by such theory-driven hypothesis testing, in part to protect against spurious correlations from blind data-mining but mainly to aid understanding. In this approach, an underlying model is proposed, the model is used to predict a potential emergent relationship between an observable and an unknown future projection, and the hypothesised emergent relationship is tested against an ensemble of GCMs.European Union Horizon 2020Engineering and Physical Sciences Research Council (EPSRC)European Research Counci

Biology Extended 1A

Exam paper (Supplementary) for second semeste

Rural Opioid Prevention and Treatment Strategies: The Experience in Four States [Working Paper]

Although opioid use rates are comparable in rural and urban counties, rural opioid users tend to be younger, unmarried, have lower incomes, and are more likely to lack health insurance, all vulnerabilities that may negatively impact their ability to seek treatment and recover. Additionally, the rural health care system is characterized by numerous resource, workforce, access, and geographic challenges that complicate the delivery of specialized care for OUDs in rural communities. The nature and scope of the opioid crisis vary across rural communities and require multifaceted, community-based strategies to address the problem. Based on interviews with key stakeholders in Indiana, North Carolina, Vermont, and Washington State, this qualitative study explores promising state and community strategies to tackle the opioid crisis in rural communities and identifies rural challenges to the provision of OUD prevention, treatment, and recovery services

Ion channels as insecticide targets.

Published onlineJournal ArticleIon channels remain the primary target of most of the small molecule insecticides. This review examines how the subunit composition of heterologously expressed receptors determines their insecticide-specific pharmacology and how the pharmacology of expressed receptors differs from those found in the insect nervous system. We find that the insecticide-specific pharmacology of some receptors, like that containing subunits of the Rdl encoded GABA receptor, can be reconstituted with very few of the naturally occurring subunits expressed. In contrast, workers have struggled even to express functional insect nicotinic acetylcholine receptors (nAChRs), and work has therefore often relied upon the expression of vertebrate receptor subunits in their place. We also examine the extent to which insecticide-resistance-associated mutations, such as those in the para encoded voltage-gated sodium channel, can reveal details of insecticide-binding sites and mode of action. In particular, we examine whether mutations are present in the insecticide-binding site and/or at sites that allosterically affect the drug preferred conformation of the receptor. We also discuss the ryanodine receptor as a target for the recently developed diamides. Finally, we examine the lethality of the genes encoding these receptor subunits and discuss how this might determine the degree of conservation of the resistance-associated mutations found

Investigating the molecular mechanisms of organophosphate and pyrethroid resistance in the fall armyworm Spodoptera frugiperda.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tThe fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain) or lambda-cyhalothrin (PYR strain) were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE) and pyrethroid (voltage-gated sodium channel, VGSC) target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS). These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results provide evidence that both target-site and metabolic mechanisms underlie the resistance of S. frugiperda to pyrethroids and organophosphates.BBSRCNational Council for Scientific and Technological Development of Brazi

Identification of the main malaria vectors in the Anopheles gambiae species complex using a TaqMan real-time PCR assay

Background: The Anopheles gambiae sensu lato species complex comprises seven sibling species of mosquitoes that are morphologically indistinguishable. Rapid identification of the two main species which vector malaria, Anopheles arabiensis and An. gambiae sensu stricto, from the non-vector species Anopheles quadriannulatus is often required as part of vector control programmes. Currently the most widely used method for species identification is a multiplex PCR protocol that targets species specific differences in ribosomal DNA sequences. While this assay has proved to be reasonably robust in many studies, additional steps are required post-PCR making it time consuming. Recently, a high-throughput assay based on TaqMan single nucleotide polymorphism genotyping that detects and discriminates An. gambiae s.s and An. arabiensis has been reported. Methods: A new TaqMan assay was developed that distinguishes between the main malaria vectors (An. Arabiensis and An. gambiae s.s.) and the non-vector An. quadriannulatus after it was found that the existing TaqMan assay incorrectly identified An. quadriannulatus, An. merus and An. melas as An. gambiae s.s. The performance of this new TaqMan assay was compared against the existing TaqMan assay and the standard PCR method in a blind species identification trial of over 450 samples using field collected specimens from a total of 13 countries in Sub-Saharan Africa. Results: The standard PCR method was found to be specific with a low number of incorrect scores (<1%), however when compared to the TaqMan assays it showed a significantly higher number of failed reactions (15%). Both the new vector-specific TaqMan assay and the exisiting TaqMan showed a very low number of incorrectly identified samples (0 and 0.54%) and failed reactions (1.25% and 2.96%). In tests of analytical sensitivity the new TaqMan assay showed a very low detection threshold and can consequently be used on a single leg from a fresh or silica-dried mosquito without the need to first extract DNA. Conclusion: This study describes a rapid and sensitive assay that very effectively identifies the two main malaria vectors of the An. gambiae species complex from the non-vector sibling species. The method is based on TaqMan SNP genotyping and can be used to screen single legs from dried specimens. In regions where An. merus/melas/ bwambae, vectors with restricted distributions, are not present it can be used alone to discriminate vector from non-vector or in combination with the Walker TaqMan assay to distinguish An. arabiensis and An. gambiae s.s

Abrupt Climate Change in an Oscillating World.

This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.The notion that small changes can have large consequences in the climate or ecosystems has become popular as the concept of tipping points. Typically, tipping points are thought to arise from a loss of stability of an equilibrium when external conditions are slowly varied. However, this appealingly simple view puts us on the wrong foot for understanding a range of abrupt transitions in the climate or ecosystems because complex environmental systems are never in equilibrium. In particular, they are forced by diurnal variations, the seasons, Milankovitch cycles and internal climate oscillations. Here we show how abrupt and sometimes even irreversible change may be evoked by even small shifts in the amplitude or time scale of such environmental oscillations. By using model simulations and reconciling evidence from previous studies we illustrate how these phenomena can be relevant for ecosystems and elements of the climate system including terrestrial ecosystems, Arctic sea ice and monsoons. Although the systems we address are very different and span a broad range of time scales, the phenomena can be understood in a common framework that can help clarify and unify the interpretation of abrupt shifts in the Earth system.This work was carried out under the program of the Netherlands Earth System Science Centre (NESSC), financially supported by the Ministry of Education, Culture and Science (OCW). We are grateful to Chris Huntingford for his constructive comments that helped us to improve the manuscript. We would also like to acknowledge Michel Crucifix, Henk Dijkstra, and Peter Cox for their helpful comments. S.B. is eternally grateful to Nina Engelhardt and the University of Edinburgh for the inspiring working conditions