Safe and just operating spaces for regional social-ecological systems

Humanity faces a major global challenge in achieving wellbeing for all, while simultaneously ensuring that the biophysical processes and ecosystem services that underpin wellbeing are exploited within scientifically informed boundaries of sustainability. We propose a framework for defining the safe and just operating space for humanity that integrates social wellbeing into the original planetary boundaries concept (Rockström et al., 2009a,b) for application at regional scales. We argue that such a framework can: (1) increase the policy impact of the boundaries concept as most governance takes place at the regional rather than planetary scale; (2) contribute to the understanding and dissemination of complexity thinking throughout governance and policy-making; (3) act as a powerful metaphor and communication tool for regional equity and sustainability. We demonstrate the approach in two rural Chinese localities where we define the safe and just operating space that lies between an environmental ceiling and a social foundation from analysis of time series drawn from monitored and palaeoecological data, and from social survey statistics respectively. Agricultural intensification has led to poverty reduction, though not eradicated it, but at the expense of environmental degradation. Currently, the environmental ceiling is exceeded for degraded water quality at both localities even though the least well-met social standards are for available piped water and sanitation. The conjunction of these social needs and environmental constraints around the issue of water access and quality illustrates the broader value of the safe and just operating space approach for sustainable development

Modelling Automation–Human Driver Handovers Using Operator Event Sequence Diagrams

This research aims to show the effectiveness of Operator Event Sequence Diagrams (OESDs) in the normative modelling of vehicle automation to human drivers’ handovers and validate the models with observations from a study in a driving simulator. The handover of control from automation to human operators has proved problematic, and in the most extreme circumstances catastrophic. This is currently a topic of much concern in the design of automated vehicles. OESDs were used to inform the design of the interaction, which was then tested in a driving simulator. This test provided, for the first time, the opportunity to validate OESDs with data gathered from videoing the handover processes. The findings show that the normative predictions of driver activity determined during the handover from vehicle automation in a driving simulator performed well, and similar to other Human Factors methods. It is concluded that OESDs provided a useful method for the human-centred automation design and, as the predictive validity shows, can continue to be used with some confidence. The research in this paper has shown that OESDs can be used to anticipate normative behaviour of drivers engaged in handover activities with vehicle automation in a driving simulator. Therefore, OESDs offer a useful modelling tool for the Human Factors profession and could be applied to a wide range of applications and domains.</jats:p

A Consensus Map in Cultivated Hexaploid Oat Reveals Conserved Grass Synteny with Substantial Subgenome Rearrangement

Citation: Chaffin, A. S., Huang, Y. F., Smith, S., Bekele, W. A., Babiker, E., Gnanesh, B. N., . . . Tinker, N. A. (2016). A Consensus Map in Cultivated Hexaploid Oat Reveals Conserved Grass Synteny with Substantial Subgenome Rearrangement. Plant Genome, 9(2), 21. doi:10.3835/plantgenome2015.10.0102Hexaploid oat (Avena sativa L., 2n = 6x = 42) is a member of the Poaceae family and has a large genome (similar to 12.5 Gb) containing 21 chromosome pairs from three ancestral genomes. Physical rearrangements among parental genomes have hindered the development of linkage maps in this species. The objective of this work was to develop a single high-density consensus linkage map that is representative of the majority of commonly grown oat varieties. Data from a cDNA-derived single-nucleotide polymorphism (SNP) array and genotyping-by-sequencing (GBS) were collected from the progeny of 12 biparental recombinant inbred line populations derived from 19 parents representing oat germplasm cultivated primarily in North America. Linkage groups from all mapping populations were compared to identify 21 clusters of conserved collinearity. Linkage groups within each cluster were then merged into 21 consensus chromosomes, generating a framework consensus map of 7202 markers spanning 2843 cM. An additional 9678 markers were placed on this map with a lower degree of certainty. Assignment to physical chromosomes with high confidence was made for nine chromosomes. Comparison of homeologous regions among oat chromosomes and matches to orthologous regions of rice (Oryza sativa L.) reveal that the hexaploid oat genome has been highly rearranged relative to its ancestral diploid genomes as a result of frequent translocations among chromosomes. Heterogeneous chromosome rearrangements among populations were also evident, probably accounting for the failure of some linkage groups to match the consensus. This work contributes to a further understanding of the organization and evolution of hexaploid grass genomes

A Consensus Map in Cultivated Hexaploid Oat Reveals Conserved Grass Synteny with Substantial Subgenome Rearrangement

Hexaploid oat ( L., 2 = 6 = 42) is a member of the Poaceae family and has a large genome (∼12.5 Gb) containing 21 chromosome pairs from three ancestral genomes. Physical rearrangements among parental genomes have hindered the development of linkage maps in this species. The objective of this work was to develop a single high-density consensus linkage map that is representative of the majority of commonly grown oat varieties. Data from a cDNA-derived single-nucleotide polymorphism (SNP) array and genotyping-by-sequencing (GBS) were collected from the progeny of 12 biparental recombinant inbred line populations derived from 19 parents representing oat germplasm cultivated primarily in North America. Linkage groups from all mapping populations were compared to identify 21 clusters of conserved collinearity. Linkage groups within each cluster were then merged into 21 consensus chromosomes, generating a framework consensus map of 7202 markers spanning 2843 cM. An additional 9678 markers were placed on this map with a lower degree of certainty. Assignment to physical chromosomes with high confidence was made for nine chromosomes. Comparison of homeologous regions among oat chromosomes and matches to orthologous regions of rice ( L.) reveal that the hexaploid oat genome has been highly rearranged relative to its ancestral diploid genomes as a result of frequent translocations among chromosomes. Heterogeneous chromosome rearrangements among populations were also evident, probably accounting for the failure of some linkage groups to match the consensus. This work contributes to a further understanding of the organization and evolution of hexaploid grass genomes

Using hypnosis to disrupt face processing: mirrored-self misidentification delusion and different visual media

Mirrored-self misidentification delusion is the belief that one’s reflection in the mirror is not oneself. This experiment used hypnotic suggestion to impair normal face processing in healthy participants and recreate key aspects of the delusion in the laboratory. From a pool of 439 participants, 22 high hypnotisable participants (“highs”) and 20 low hypnotisable participants were selected on the basis of their extreme scores on two separately administered measures of hypnotisability. These participants received a hypnotic induction and a suggestion for either impaired (i) self-face recognition or (ii) impaired recognition of all faces. Participants were tested on their ability to recognize themselves in a mirror and other visual media – including a photograph, live video, and handheld mirror – and their ability to recognize other people, including the experimenter and famous faces. Both suggestions produced impaired self-face recognition and recreated key aspects of the delusion in highs. However, only the suggestion for impaired other-face recognition disrupted recognition of other faces, albeit in a minority of highs. The findings confirm that hypnotic suggestion can disrupt face processing and recreate features of mirrored-self misidentification. The variability seen in participants’ responses also corresponds to the heterogeneity seen in clinical patients. An important direction for future research will be to examine sources of this variability within both clinical patients and the hypnotic model

Connectivity and zebra mussel invasion offer short‐term buffering of eutrophication impacts on floodplain lake landscape biodiversity

Aim To investigate if connectivity and zebra mussel (Dreissena polymorpha) occurrence can mitigate effects of eutrophication in a lowland lake landscape. Location Upper Lough Erne, Northern Ireland, UK. Methods Data on environment, macrophytes and invertebrates were assembled for three basins of a large central lake and its satellite floodplain lakes via field surveys and palaeolimnological analyses. Space–time interaction analyses of palaeoecological data were compared pre‐1950 and post‐1950. Multivariate analyses examined how connectivity, environment and zebra mussels influenced contemporary lake communities, and explain their divergence from historical communities in the past. Results Pre‐1950, we found high community variation across sites and low within‐lake variation in macrophytes, but progressive eutrophication accentuated within‐lake community variation after 1950. Partitioning analysis showed larger effects of connectivity than nutrient enrichment on contemporary macrophyte composition, while local effects structured invertebrate communities. Three clusters of lakes were revealed according to variation in macrophyte composition, isolation from the central lake and nutrient enrichment: Group 1– the central lake and six nearby lakes were meso‐eutrophic (TP = 66.7 ± 47.6 μg/L; TN = 0.79 ± 0.41 mg/L) and had the highest zebra mussel abundances and organismal biodiversity; Group 2– Eight eutrophic (TP = 112±36.6 μg/L; TN = 1.25 ± 0.5 mg/L) and connected lakes; Group 3– Seven isolated and hypertrophic (TP = 163.2 ± 101.5 μg/L; TN = 1.55 ± 0.3 mg/L) lakes. Pre‐1950 palaeolimnological data for macrophytes and invertebrates for 5 lakes and a basin in the central lake most resembled extant lake communities of Group 1. However, palaeo‐records revealed that macrophytes and invertebrates subsequently converged towards those of Groups 2 and 3. Main conclusions Our study reveals that the central “mother” lake acts as a hub for preserving biodiversity via shared hydrological connectivity with satellite lakes and high zebra mussel abundances. These may buffer the impoverishing effects of eutrophication and sustain unexpectedly high biodiversity in the short term. Such protective buffering, however, cannot be relied upon indefinitely to conserve biodiversity

The Immune System in Stroke

Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome. Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infection - similar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.