The circular economy: An interdisciplinary exploration of the concept and application in a global context

There have long been calls from industry for guidance in implementing strategies for sustainable development. The Circular Economy represents the most recent attempt to conceptualize the integration of economic activity and environmental wellbeing in a sustainable way. This set of ideas has been adopted by China as the basis of their economic development (included in both the 11th and the 12th ‘Five Year Plan’), escalating the concept in minds of western policymakers and NGOs. This paper traces the conceptualisations and origins of the Circular Economy, tracing its meanings, and exploring its antecedents in economics and ecology, and discusses how the Circular Economy has been operationalized in business and policy. The paper finds that while the Circular Economy places emphasis on the redesign of processes and cycling of materials, which may contribute to more sustainable business models, it also encapsulates tensions and limitations. These include an absence of the social dimension inherent in sustainable development that limits its ethical dimensions, and some unintended consequences. This leads us to propose a revised definition of the Circular Economy as “an economic model wherein planning, resourcing, procurement, production and reprocessing are designed and managed, as both process and output, to maximize ecosystem functioning and human well-being”

The Circular Economy: An Interdisciplinary Exploration of the Concept and Application in a Global Context

There have long been calls from industry for guidance in implementing strategies for sustainable development. The Circular Economy represents the most recent attempt to conceptualize the integration of economic activity and environmental wellbeing in a sustainable way. This set of ideas has been adopted by China as the basis of their economic development (included in both the 11th and the 12th ‘Five Year Plan’), escalating the concept in minds of western policymakers and NGOs. This paper traces the conceptualisations and origins of the Circular Economy, tracing its meanings, and exploring its antecedents in economics and ecology, and discusses how the Circular Economy has been operationalized in business and policy. The paper finds that while the Circular Economy places emphasis on the redesign of processes and cycling of materials, which may contribute to more sustainable business models, it also encapsulates tensions and limitations. These include an absence of the social dimension inherent in sustainable development that limits its ethical dimensions, and some unintended consequences. This leads us to propose a revised definition of the Circular Economy as “an economic model wherein planning, resourcing, procurement, production and reprocessing are designed and managed, as both process and output, to maximize ecosystem functioning and human well-being”

Forest Soil Water in Landscape Context

Forests play an irreplaceable role in linking the water cycle with the functions of soil. Soil water not only enhances the stability of forests, but also its run-off and evaporation affects the growth of plants in different ecosystems. The forest soil water balance is contextualized within the immediate and more global landscapes, in terms of relations of water to the soil environment and bedrock, participation in the local water cycle within a catchment basin and in the global cycle between ecosystems. Modifications by human civilization can have significant impacts, including erosion intensification, eutrophication, salinization, spreading of single-species plantations, and regime shifts. Forests regulate the movement of water in the soil environment by reducing the intensity of run-off. Such moderated run-off prevents the occurrence of flash floods, maintaining continuous availability of water for plant and human use. Participation of soil water in the cycling of elements in forests is modified by soil organic matter balance. The preservation of hydric functions in forest soils depends on prioritization of water balance restoration in every catchment basin enclosing the local element cycle. More fundamentally, the development of a synergistically interlinked system, centered around the soil-forest-water-civilization nexus, must become an urgent priority

Orphan CpG Islands Identify Numerous Conserved Promoters in the Mammalian Genome

CpG islands (CGIs) are vertebrate genomic landmarks that encompass the promoters of most genes and often lack DNA methylation. Querying their apparent importance, the number of CGIs is reported to vary widely in different species and many do not co-localise with annotated promoters. We set out to quantify the number of CGIs in mouse and human genomes using CXXC Affinity Purification plus deep sequencing (CAP-seq). We also asked whether CGIs not associated with annotated transcripts share properties with those at known promoters. We found that, contrary to previous estimates, CGI abundance in humans and mice is very similar and many are at conserved locations relative to genes. In each species CpG density correlates positively with the degree of H3K4 trimethylation, supporting the hypothesis that these two properties are mechanistically interdependent. Approximately half of mammalian CGIs (>10,000) are “orphans” that are not associated with annotated promoters. Many orphan CGIs show evidence of transcriptional initiation and dynamic expression during development. Unlike CGIs at known promoters, orphan CGIs are frequently subject to DNA methylation during development, and this is accompanied by loss of their active promoter features. In colorectal tumors, however, orphan CGIs are not preferentially methylated, suggesting that cancer does not recapitulate a developmental program. Human and mouse genomes have similar numbers of CGIs, over half of which are remote from known promoters. Orphan CGIs nevertheless have the characteristics of functional promoters, though they are much more likely than promoter CGIs to become methylated during development and hence lose these properties. The data indicate that orphan CGIs correspond to previously undetected promoters whose transcriptional activity may play a functional role during development

Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome

The possibility that alterations in DNA methylation are mechanistic drivers of development, aging and susceptibility to disease is widely acknowledged, but evidence remains patchy or inconclusive. Of partic-ular interest in this regard is the brain, where it has been reported that DNA methylation impacts on neu-ronal activity, learning and memory, drug addiction and neurodegeneration. Until recently, however, lit-tle was known about the ‘landscape ’ of the human brain methylome. Here we assay 1.9 million CpGs in each of 43 brain samples representing different individuals and brain regions. The cerebellum was a consistent outlier compared to all other regions, and showed over 16 000 differentially methylated re-gions (DMRs). Unexpectedly, the sequence charac-teristics of hypo- and hypermethylated domains in cerebellum were distinct. In contrast, very few DMRs distinguished regions of the cortex, limbic system and brain stem. Inter-individual DMRs were readily detectable in these regions. These results lead to the surprising conclusion that, with the exception of cerebellum, DNA methylation patterns are more ho-mogeneous between different brain regions from the same individual, than they are for a single brain re-gion between different individuals. This finding sug-gests that DNA sequence composition, not develop-mental status, is the principal determinant of the hu-man brain DNA methylome

CpG islands influence chromatin structure via the CpG-binding protein Cfp1

CpG islands (CGIs) are prominent in the mammalian genome owing to their GC-rich base composition and high density of CpG dinucleotides(1,2). Most human gene promoters are embedded within CGIs that lack DNA methylation and coincide with sites of histone H3 lysine 4 trimethylation (H3K4me3), irrespective of transcriptional activity(3,4). In spite of these intriguing correlations, the functional significance of non-methylated CGI sequences with respect to chromatin structure and transcription is unknown. By performing a search for proteins that are common to all CGIs, here we show high enrichment for Cfp1, which selectively binds to non-methylated CpGs in vitro(5,6). Chromatin immunoprecipitation of a mono-allelically methylated CGI confirmed that Cfp1 specifically associates with non-methylated CpG sites in vivo. High throughput sequencing of Cfp1-bound chromatin identified a notable concordance with non-methylated CGIs and sites of H3K4me3 in the mouse brain. Levels of H3K4me3 at CGIs were markedly reduced in Cfp1-depleted cells, consistent with the finding that Cfp1 associates with the H3K4 methyltransferase Setd1 (refs 7, 8). To test whether non-methylated CpG-dense sequences are sufficient to establish domains of H3K4me3, we analysed artificial CpG clusters that were integrated into the mouse genome. Despite the absence of promoters, the insertions recruited Cfp1 and created new peaks of H3K4me3. The data indicate that a primary function of non-methylated CGIs is to genetically influence the local chromatin modification state by interaction with Cfp1 and perhaps other CpG-binding proteins

Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state

MeCP2 is a nuclear protein with an affinity for methylated DNA that can recruit histone deacetylases. Deficiency or excess of MeCP2 causes severe neurological problems, suggesting that the number of molecules per cell must be precisely regulated. We quantified MeCP2 in neuronal nuclei and found that it is nearly as abundant as the histone octamer. Despite this high abundance, MeCP2 associates preferentially with methylated regions and high-throughput sequencing showed that its genome-wide binding tracks methyl-CpG density. MeCP2 deficiency results in global changes in neuronal chromatin structure, including elevated histone acetylation and a doubling of histone H1. Neither change is detectable in glia, where MeCP2 occurs at lower levels. The mutant brain also shows elevated transcription of repetitive elements. Our data argue that MeCP2 may not act as a gene-specific transcriptional repressor in neurons, but might instead dampen transcriptional noise genome-wide in a DNA methylation-dependent manner

Religious Reasons for Campbell's View of Emotional Appeals in Philosophy of Rhetoric

This is the author's accepted manuscript.Reading Campbell's Philosophy of Rhetoric from a rhetorical perspective--as an attempt to address issues relevant to religious rhetoric--I argue that Campbell's aims of preparing future ministers to preach and defending the authority of revealed religion shaped, first, his conception of inventing and presenting emotional appeals and, second, his key assumptions about reason and passion. The essay adds a chapter to accounts of the relationship between reason and passion in sacred rhetorics and in rhetorical traditions more generally, and addresses the question of what Campbell's theory of rhetoric may aim to inculcate or cultivate emotionally and why

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting. Funding British Heart Foundation

Life’s a Gas: A Thermodynamic Theory of Biological Evolution

This paper outlines a thermodynamic theory of biological evolution. Beginning with a brief summary of the parallel histories of the modern evolutionary synthesis and thermodynamics, we use four physical laws and processes (the first and second laws of thermodynamics, diffusion and the maximum entropy production principle) to frame the theory. Given that open systems such as ecosystems will move towards maximizing dispersal of energy, we expect biological diversity to increase towards a level, Dmax, representing maximum entropic production (Smax). Based on this theory, we develop a mathematical model to predict diversity over the last 500 million years. This model combines diversification, post-extinction recovery and likelihood of discovery of the fossil record. We compare the output of this model with that of the observed fossil record. The model predicts that life diffuses into available energetic space (ecospace) towards a dynamic equilibrium, driven by increasing entropy within the genetic material. This dynamic equilibrium is punctured by extinction events, which are followed by restoration of Dmax through diffusion into available ecospace. Finally we compare and contrast our thermodynamic theory with the MES in relation to a number of important characteristics of evolution (progress, evolutionary tempo, form versus function, biosphere architecture, competition and fitness)