Feedbacks and social tipping: A dynamic systems approach to rapid decarbonization

Social tipping points are promising levers for accelerating progress towards net-zero greenhouse gas emission targets. They describe how social, political, economic or technological systems can move rapidly into a new state if cascading positive feedback mechanisms are triggered. Analysing the potential for social tipping requires considering the inherent complexity of social systems and their feedbacks. Here, drawing on insights from an expert elicitation workshop, we outline a dynamic systems approach that entails i) a systems outlook involving interconnected feedback mechanisms alongside cross-system and cross-scale interactions, ii) directed data collection efforts to provide empirical evidence and monitoring of social tipping dynamics, and iii) global, integrated, descriptive modelling to project future dynamics and provide ex-ante evidence for interventions aiming to trigger positive feedback mechanisms. We argue how and why this approach will strengthen the climate policy relevance of research on social tipping

A dynamic systems approach to harness the potential of social tipping

Social tipping points are promising levers to achieve net-zero greenhouse gas emission targets. They describe how social, political, economic or technological systems can move rapidly into a new state if cascading positive feedback mechanisms are triggered. Analysing the potential of social tipping for rapid decarbonization requires considering the inherent complexity of social systems. Here, we identify that existing scientific literature is inclined to a narrative-based account of social tipping, lacks a broad empirical framework and a multi-systems view. We subsequently outline a dynamic systems approach that entails (i) a systems outlook involving interconnected feedback mechanisms alongside cross-system and cross-scale interactions, and including a socioeconomic and environmental injustice perspective (ii) directed data collection efforts to provide empirical evidence for and monitor social tipping dynamics, (iii) global, integrated, descriptive modelling to project future dynamics and provide ex-ante evidence for interventions. Research on social tipping must be accordingly solidified for climate policy relevance

Plate-boundary deformation associated with the great Sumatra–Andaman earthquake

The Sumatra–Andaman earthquake of 26 December 2004 is the first giant earthquake (moment magnitude M_w > 9.0) to have occurred since the advent of modern space-based geodesy and broadband seismology. It therefore provides an unprecedented opportunity to investigate the characteristics of one of these enormous and rare events. Here we report estimates of the ground displacement associated with this event, using near-field Global Positioning System (GPS) surveys in northwestern Sumatra combined with in situ and remote observations of the vertical motion of coral reefs. These data show that the earthquake was generated by rupture of the Sunda subduction megathrust over a distance of >1,500 kilometres and a width of <150 kilometres. Megathrust slip exceeded 20 metres offshore northern Sumatra, mostly at depths shallower than 30 kilometres. Comparison of the geodetically and seismically inferred slip distribution indicates that ~30 per cent additional fault slip accrued in the 1.5 months following the 500-second-long seismic rupture. Both seismic and aseismic slip before our re-occupation of GPS sites occurred on the shallow portion of the megathrust, where the large Aceh tsunami originated. Slip tapers off abruptly along strike beneath Simeulue Island at the southeastern edge of the rupture, where the earthquake nucleated and where an M_w = 7.2 earthquake occurred in late 2002. This edge also abuts the northern limit of slip in the 28 March 2005 M_w = 8.7 Nias–Simeulue earthquake

Health-related quality of life in patients with inoperable malignant bowel obstruction: secondary outcome from a double-blind, parallel, placebo-controlled randomised trial of octreotide.

BACKGROUND:This analysis aims to evaluate health-related quality of life (HrQoL) (primary outcome for this analysis), nausea and vomiting, and pain in patients with inoperable malignant bowel obstruction (IMBO) due to cancer or its treatments randomised to standardised therapies plus octreotide or placebo over a maximum of 72 h in a double-blind clinical trial. METHODS:Adults with IMBO and vomiting recruited through 12 services spanning inpatient, consultative and community settings in Australia were randomised to subcutaneous octreotide infusion or saline. HrQoL was measured at baseline and treatment cessation (EORTC QLQ-C15-PAL). Mean within-group paired differences between baseline and post-treatment scores were analysed using Wilcoxon Signed Rank test and between group differences estimated using linear mixed models, adjusted for baseline score, sex, age, time, and study arm. RESULTS:One hundred six of the 112 randomised participants were included in the analysis (n = 52 octreotide, n = 54 placebo); 6 participants were excluded due to major protocol violations. Mean baseline HrQoL scores were low (octreotide 22.1, 95% CI 14.3, 29.9; placebo 31.5, 95% CI 22.3, 40.7). There was no statistically significant within-group improvement in the mean HrQoL scores in the octreotide (p = 0.21) or placebo groups (p = 0.78), although both groups reported reductions in mean nausea and vomiting (octreotide p < 0.01; placebo p = 0.02) and pain scores (octreotide p < 0.01; placebo p = 0.03). Although no statistically significant difference in changes in HrQoL scores between octreotide and placebo were seen, an adequately powered study is required to fully assess any differences in HrQoL scores. CONCLUSION:The HrQoL of patients with IMBO and vomiting is poor. Further research to formally evaluate the effects of standard therapies for IMBO is therefore warranted. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry ACTRN12608000211369 (date registered 18/04/2008)

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

Sertraline in symptomatic chronic breathlessness: a double blind, randomised trial

Copyright ©ERS 2019. Does sertraline provide symptomatic relief for chronic breathlessness in people with advanced disease whose underlying cause(s) are optimally treated?223 participants with chronic breathlessness (modified Medical Research Council breathlessness scale ≥2) who had optimal treatment of underlying cause(s) were randomised 1:1 to sertraline 25-100 mg (titrated upwards over 9 days) or placebo for 4 weeks. The primary outcome was the proportion who had an improvement in intensity of current breathlessness >15% from baseline on a 100-mm visual analogue scale.The proportion of people responding to sertraline was similar to placebo for current breathlessness on days 26-28 (OR 1.00, 95% CI 0.71-1.40) and for other measures of breathlessness. Quality of life in the sertraline arm had a higher likelihood of improving than in the placebo arm over the 4 weeks (OR 0.21, 95% CI 0.01-0.41; p=0.044). No differences in performance status, anxiety and depression, or survival were observed. Adverse event rates were similar between arms.Sertraline does not appear to provide any benefit over placebo in the symptomatic relief of chronic breathlessness in this patient population

Spatial migration of temporal earthquake clusters driven by the transfer of differential stress between neighbouring fault/shear-zone structures

Uncertainty concerning the processes responsible for slip-rate fluctuations associated with temporal clustering of surface faulting earthquakes is a fundamental, unresolved issue in tectonics, because strain-rates accommodated by fault/shear-zone structures are the key to understanding the viscosity structure of the crust and seismic hazard. We constrain the timing and amplitude of slip-rate fluctuations that occurred on three active normal faults in central Italy over a time period of 20–30 kyrs, using in situ 36Cl cosmogenic dating of fault planes. We identify five periods of rapid slip on individual faults lasting a few millennia, separated time periods of up to 10 millennia with low or zero slip-rate. The rapid slip pulses migrated across the strike between the faults in two waves from SW to NE. We replicate this migration with a model where rapid slip induces changes in differential stress that drive changes in strain-rate on viscous shear zones that drive slip-rate variability on overlying brittle faults. Earthquakes increase the differential stress and strain-rate on underlying shear zones, which in turn accumulate strain, re-loading stress onto the overlying brittle fault. This positive feedback produces high strain-rate episodes containing several large magnitude surface faulting earthquakes (earthquake clusters), but also reduce the differential stress on the viscous portions of neighbouring fault/shear-zones slowing the occurrence of large-magnitude surface faulting earthquakes (earthquake anticlusters). Shear-zones on faults experiencing anticlusters continue to accumulate viscous strain at a lowered rate, and eventually this loads the overlying brittle fault to failure, initiating a period of rapid slip through the positive feedback process described above, and inducing lowered strain-rates onto neighbouring fault/shear-zones. We show that these patterns of differential stress change can replicate the measured earthquake clustering implied by the 36Cl data. The stress changes are related to the fault geometry in terms of distance and azimuth from the slipping structure, implying that (a) strain-rate and viscosity fluctuations for studies of continental rheology, and (b) slip-rates for seismic hazard purposes are to an extent predictable given knowledge of the fault system geometry

Beyond Teenage and Young Adult Cancer Care: Care Experiences of Patients Aged 25-39 Years Old in the UK National Health Service.

AimsAdolescents and young adults aged 15-39 years with cancer face unique medical, practical and psychosocial issues. In the UK, principal treatment centres and programmes have been designed to care for teenage and young adult patients aged 13-24 years in an age-appropriate manner. However, for young adults (YAs) aged 25-39 years with cancer, little access to age-specific support is available. The aim of this study was to examine this possible gap by qualitatively exploring YA care experiences, involving patients as research partners in the analysis to ensure robust results.Materials and methodsWe conducted a phenomenological qualitative study with YAs diagnosed with any cancer type between ages 25 and 39 years old in the last 5 years. Participants took part in interviews or focus groups and data were analysed using inductive thematic analysis. Results were shaped in an iterative process with the initial coders and four YA patients who did not participate in the study to improve the rigor of the results.ResultsSixty-five YAs with a range of tumour types participated. We identified seven themes and 13 subthemes. YAs found navigating the healthcare system difficult and commonly experienced prolonged diagnostic pathways. Participants felt under-informed about clinical details and the long-term implications of side-effects on daily life. YAs found online resources overwhelming but also a source of information and treatment support. Some patients regretted not discussing fertility before cancer treatment or felt uninformed or rushed when making fertility preservation decisions. A lack of age-tailored content or age-specific groups deterred YAs from accessing psychological support and rehabilitation services.ConclusionsYAs with cancer may miss some benefits provided to teenagers and young adults in age-tailored cancer services. Improving services for YAs in adult settings should focus on provision of age-specific information and access to existing relevant support