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There has been significant growth in interest in the circular economy (“CE”) concept as a transformative solution to the prevailing linear economy, helping to solve various economic, environmental and social challenges. Nevertheless, pertinent issues such as societal inclusion, well-being and equity remain peripheral in the contemporary CE debate. Fulfilling human needs has been recognised as a prerequisite for sustainable development and was implicitly and explicitly prevalent in parts of the seminal material on which the CE is based. However, the contemporary use of the concept by business has left it bereft of any convincing evidence that a CE will satisfy needs in a radically different way to the existing linear economy. As a result, there are few practical cases for business learning, and even fewer in a developing world context. This study explores a unique business venture implemented by a Vietnam-based denim manufacturer, which simultaneously tackles two key development challenges: The inclusion of vulnerable communities and sustainable resource use. The venture employs persons with disabilities and utilises textile by-products from the core production to produce a range of upcycled items (e.g., bags, cushion covers etc). This forms part of a broader company-wide social sustainability and CE strategy. We utilise Max-Neef's Human-Scale Development proposal as a lens explore how the venture can support need satisfaction of these employees while being environmentally sustainable. We seek to provide a compelling practical case to illustrate how social impact and circularity can be simultaneously enhanced at the micro-level.

In current supply chains, material suppliers sell raw material resources to producers who sub-sequentially sell produced resourced to consumers. Ownership of resources, therefore, shifts from a few organisations to many consumers who are responsible to deal with them at the end of life. Product-service systems are business models where producers retaining ownership of produced resources have increased control on obsolete resources. Motivated by the need to facilitate an unlimited use of materials and eliminate waste, this research has introduced the concept of material-service systems, which are business models where material suppliers offer materials as a service to product producers. These systems offer the advantage that material suppliers are in control of resources and are incentivized to revalorise them. A scenario is explored in which a material-service system operates in conjunction with a product-service system and one in which it functions on its own. Finally, the benefits and incentives of the proposed service systems are discussed along with potential enablers and challenges.

The Circular Economy (“CE”) is gaining momentum as an approach to addressing sustainability challenges. The CE is framed as a transformative model with economic, environmental and social benefits. Nevertheless, the degree of circularity in the global economy is low and critics highlight that current interpretations fall short in delivering promised results regarding the social dimension of sustainability. Instead economic growth is elevated above more radical socio-environmental transformation. This exploratory paper adopts a human needs approach, using Max-Neef’s Human-Scale Development proposal as an analytical lens to explore the contentious social dimension of the CE. The study revisits four seminal texts which are commonly referenced as influencing the CE’s conceptual development: The Blue Economy; Cradle to Cradle; Regenerative Design for Sustainable Development; and, The Performance Economy. These texts were analysed to identify satisfiers of human needs. This provides insight into how inclusive earlier visualisations were of encompassing human needs, and how these compare to the current CE direction. We argue that satisfiers of human needs are embedded, to differing extents, in some of the early CE depictions. Nevertheless, the CE concept has selectively developed, neglecting radical, human-centric transformational aspects and instead adheres to a familiar pathway of business-led economic growth.

Sustainable green chemistry depends on technically feasible, cost-effective and socially acceptable decisions by regulators, industry and the wider community. The discipline needs to embrace a new suite of tools and train proponents in their use. We propose a set of tools that will bridge the gap between technical feasibility and efficiency on one hand, and social preferences and values on the other. We argue that they are indispensable in the next generation of regulators and chemistry industry proponents.

Conceptualising firms from a business ecosystem, value-, or supply- network perspective captures the boundary-spanning nature of value creation. However, the relationship dynamics that enable or inhibit sustainable value creation, as well as the understanding of how to resolve trade-offs in sustainable supply chain management (SSCM), need to be better understood. To explore these, we present a comparative case study of how situational logics and power relations are embedded in business models within a UK brewer and its malt supply chain. The exploratory case illustrates how network-centric business model innovation (BMI) resolves the trade-off between economic and environmental value through the prioritisation of sustainability-related ‘cultural’ resources. These findings suggest that organisations seeking to implement sustainable supply networks need to pay greater attention to how they use business model innovation to institutionalise situational logics that enable or inhibit sustainable value creation and resolve trade-offs.

This paper draws on material entropy and life cycle thinking to develop the Resource States framework. This framework clarifies and systematises the language around resources within the circular economy (CE) discourse, such that insights from different tools and approaches that investigate different aspects of CE can be aggregated and a more comprehensive picture of complex circular systems can be compiled. Currently, progress of the CE discourse is hampered by a lack of a clear and systematic approach to what we refer to as the particle state and the product state. That is: whether to approach resource circulation from the perspective of elements, molecules or materials; or whether to adopt the perspective of products or finished goods. As these two perspectives are often implicit in current contributions to CE, we first articulate both approaches, before assessing their respective contributions and limitations. Next, we draw on material entropy and life cycle thinking to integrate both perspectives and develop a more comprehensive way of conceptualising resource states, in the form of the Resource States framework. We furthermore present how this framework can be used A) to clearly distinguish between circular strategies, as well as between different implementation scenarios of the same circular strategy; B) to systematically explore and map synergies and trade-offs between combinations of circular strategies; and C) to link circular strategies with structural waste present in a given context. Lastly, we discuss the strengths and weaknesses of the framework and reflect on how it advances the CE field.

Urban-led change for sustainability is a key site of intervention in delivering the ambitions of the Sustainable Development Goals. Within this broad discourse, four umbrella concepts have emerged in recent decades: urban sustainability, urban transitions, urban transformation and urban resilience. This literature review aims to offer a qualitative assessment of the types of interventions currently being advocated for in academic-led literature. Firstly, the paper presents an overview of the concepts and summarises current gaps; secondly, it uses Donella Meadows' Leverage Points as analytical framework to categorise and discuss interventions supported in the literature. Our findings indicate that although the literature advocates for systemic change towards sustainability as an outcome of a large palette of urban interventions, less consideration is given to the means of achieving these. The findings highlight the need to focus on processes as much as on outcomes when advocating, devising or implementing interventions. This requires a process of understanding and negotiating trade-offs and the different worldviews and values that underpin them. Addressing this entails going beyond technocratic skills through cultivating reflexivity, effective communities of practice and new forms of organising for knowledge production, as well as interrogate our roles and agency as urban researchers.

The research starts from the premise that as the world is changing rapidly and in nonlinear ways, we are educating future practitioners for jobs and contexts that don’t yet exist. They instead need to be equipped to work for and with uncertainty to be able to grapple with the scale and pace of emergent change. The fields of design and futures studies bring significant insights to this challenge, including an array of methods, tools, and frameworks for prospective and systemic explorations of alternative futures. The emerging field of design futures can be framed as ways to develop and deploy prompts, artifacts, and narratives to critically interrogate tomorrow’s societal debates today; as such, it is intentional from the outset in its pursuit of preferable futures and therefore social and environmental justice. The process of imagining the future is an active, values-laden social practice, which requires a layered approach to a methodology to surface and challenge dominant patterns—making it an ideal approach for training the young people who will shape our future. This article reports on the design and delivery of participatory workshops that employ design futures methods to facilitate the exploration of transformative change for sustainability. These workshops were conducted with young people aged sixteen to seventeen to equip them to develop and explore alternative futures. The results suggest that design futures methods can facilitate participants from non-design backgrounds to develop alternative futures and artifacts that might sit within them. It was found that developing a sense of ownership was key to enabling participants to effectively reflect on alternative futures and their implications. Finally, the study highlights the potential for these methods to inform both design and sustainability pedagogy.

The lack of progress in the face of complex sustainability challenges has in part been attributed to a lack of imagination, rather than awareness. Nurturing and surfacing pluralistic alternative futures, as well imagining the pathways that might get us there, are key processes in bridging this imagination gap. The emerging field of design futures provides methods and tools to develop narratives as well as tangible artefacts depicting products, services and experiences set within alternative futures. These methods build on long-established interdisciplinary inquiries into how and why people develop images of the futures. The present research aims to explore young people’s images of the future (set in 2068 and 2038) through design futures methods. This paper presents the outcomes of a series of workshops in which over 70 young people (aged 16–17) imagined a series of alternative futures and developed artefacts that support the pathways towards these futures. The results reveal that while design futures methods are effective in developing and interrogating collective future imaginaries, deeper challenges rooted in the homogeneity of dominant Western imaginaries and the hyper–individualistic turn of late–modernity remain.

Successful entrepreneurship relies on the development of an idea and its execution in such a way that value is captured. The idea of value, however, is often framed solely as market return, rather than a more inclusive understanding of value as social good. Ethical and normative considerations are often ‘nice to have’ and treated, if at all, as an add-on rather than an integrated part of doing business. In this paper, I describe a pedagogical module for ‘sustainability entrepreneurs’ that has been developed as part of an MSc course at Imperial College London. Students are challenged to develop business models that have a well-integrated environmental, social and economic value proposition and challenge the dominant neoliberal business rhetoric. The key skill developed through the module is critical reflexivity. This allows students to see that they could shape the world through their own agency and break out of conventional modes of doing business to place values at the heart of their business models.

This research aimed to develop a simple but robust method to identify the key barriers to the transition from a linear to a circular economy (CE) for end of life products or material. Nine top-tier barrier categories have been identified that influence this transition. These relate to the basic material properties and product characteristics, the availability of suitable processing technology, the environmental impacts associated with current linear management, the organizational context, industry and supply chain issues, external drivers, public perception, the regulatory framework and the overall economic viability of the transition. The method provides a novel and rapid way to identify and quantitatively assess the barriers to the development of CE products. This allows mitigation steps to be developed in parallel with new product design. The method has been used to assess the potential barriers to developing a circular economy for waste feathers generated by the UK poultry industry. This showed that transitioning UK waste feathers to circularity faces significant barriers across numerous categories and is not currently economically viable. The assessment method developed provides a novel approach to identifying barriers to circularity and has potential to be applied to a wide range of end of life materials and products.

International audience; In a context of increased land and natural resources scarcity, the possibilities for local authorities and stakeholders of anticipating evolutions or testing the impact of envisaged developments through scenario simulation are new challenges. PRECOS's approach integrates data pertaining to the fields of water and soil resources, agronomy, urbanization, land use and infrastructure etc. It is complemented by a socio-economic and regulatory analysis of the territory illustrating its constraints and stakes. A modular architecture articulates modeling software and spatial and temporal representations tools. It produces indicators in three core domains: soil degradation, water and soil resources and agricultural production. As a territory representative of numerous situations of the Mediterranean Basin (urban pressures, overconsumption of spaces, degradation of the milieus), a demonstration in the Crau's area (Southeast of France) has allowed to validate a prototype of the approach and to test its feasibility in a real life situation. Results on the Crau area have shown that, since the beginning of the 16th century, irrigated grasslands are the cornerstones of the anthropic-system, illustrating how successfully men's multi secular efforts have maintained a balance between environment and local development. But today the ecosystem services are jeopardized firstly by urban sprawl and secondly by climate change. Pre-diagnosis in regions of Emilia-Romagna (Italy) and Valencia (Spain) show that local end-users and policy-makers are interested by this approach. The modularity of indicator calculations and the availability of geodatabases indicate that PRECOS may be up scaled in other socio-economic contexts. (C) 2016 Elsevier Ltd. All rights reserved.

We report a case of traumatic upper limb injury that resulted in above elbow amputation. A multimodal approach was employed to optimize postoperative analgesia; this included continuous peripheral nerve blockade, initiated intraoperatively. Surgical access onto the axillary artery for proximal vascular control allowed placement of the nerve catheter under direct vision onto the brachial plexus. The pathophysiology of phantom pain is related to our case experience. This report highlights the complex challenge of controlling pain in combat casualties and promotes employment of multimodal analgesic strategies, including advanced regional anesthesia, in the military setting.

Business experimentation is a key avenue for accelerating change for sustainability. In contrast to experimentation in natural sciences, benefitting from controlled situations, business experimentation aims to explore the diverse possibilities that a business could create value from, or understand what works in which particular situations in a real life business context. While at present most popular with start-ups, this paper argues that large businesses can also find inspiration in business experimentation to develop sustainable business models and accelerate positive change for sustainability. Five illustrative cases are included of business experimentation for sustainability by focusing on pivots (modifications) in the business model. This paper only scratches the surface of the potential impactful new research field of business (model) experimentation for sustainability. Future work on sustainable business experimentation for start-ups and mature businesses is viewed as a powerful future research avenue to accelerate change in industries.

Traditional production frameworks and business models are now being challenged by alternatives that are informed by biology. The alternative paradigm, based on ecosystem models, argues that shifting from linear modes of production to a circular system can address material and energy efficiency by reducing the total volume of raw materials needed when manufacturing consumer products. This chapter introduces frameworks that apply closed-loop models at the product level namely; the Performance Economy, Cradle-to-CradleTM design, The Blue Economy and the Circular Economy. We discuss the historic development of these ideas and their main contributions. Through the use of examples we explore both practical challenges associated with realising circular strategies as well as their business model implications. We conclude by highlighting some of the theoretical challenges associated with adopting closed-loop models advocating for a critical approach to sustainable resource management which includes circular strategies as part of a toolbox of options.

Small research-based pharmaceutical start-ups often lack the budget and do not have the infrastructure available to apply all possible techniques for compound selection. This review details our use of a range of techniques such as high-throughput docking and similarity searching to maximize the success rate when attempting to identify pharmaceutically relevant ligands in a resource-constrained environment.

Dipeptidyl peptidase IV (DPPIV) is a member of the prolyl oligopeptidase family of serine proteases. DPPIV removes dipeptides from the N terminus of substrates, including many chemokines, neuropeptides, and peptide hormones. Specific inhibition of DPPIV is being investigated in human trials for the treatment of type II diabetes. To understand better the molecular determinants that underlie enzyme catalysis and substrate specificity, we report the crystal structures of DPPIV in the free form and in complex with the first 10 residues of the physiological substrate, Neuropeptide Y (residues 1-10; tNPY). The crystal structure of the free form of the enzyme reveals two potential channels through which substrates could access the active site-a so-called propeller opening, and side opening. The crystal structure of the DPPIV/tNPY complex suggests that bioactive peptides utilize the side opening unique to DPPIV to access the active site. Other structural features in the active site such as the presence of a Glu motif, a well-defined hydrophobic S1 subsite, and minimal long-range interactions explain the substrate recognition and binding properties of DPPIV. Moreover, in the DPPIV/tNPY complex structure, the peptide is not cleaved but trapped in a tetrahedral intermediate that occurs during catalysis. Conformational changes of S630 and H740 between DPPIV in its free form and in complex with tNPY were observed and contribute to the stabilization of the tetrahedral intermediate. Our results facilitate the design of potent, selective small molecule inhibitors of DPPIV that may yield compounds for the development of novel drugs to treat type II diabetes.

Knowledge of the 3D structure of proteins can play a key role in both understanding the biochemical function of protein targets, and developing small-molecule drugs that interact with these targets. This review will discuss recent advances in automation and miniaturization, which are making the determination of protein structures faster, more reliable, and more economical than has been possible historically.

This review explores some of the techniques available to the computational chemist to maximise the success rate when attempting to identify pharmaceutically relevant ligands in a discovery environment. The authors introduce and discuss methods of constructing various types of compound collections and consider an alternative approach to measuring compound similarity. The discussion is illustrated with an example of a kinase collection constructed using these methods and the results obtained from it. As an example of predicting absorption, distribution, metabolism, excretion and toxicology liabilities, this review focuses on the CYP450 isozyme family. The field of high-throughput docking is touched on with further examples and discussion.

Cytochrome P450 2D6 is a heme-containing enzyme that is responsible for the metabolism of at least 20% of known drugs. Substrates of 2D6 typically contain a basic nitrogen and a planar aromatic ring. The crystal structure of human 2D6 has been solved and refined to 3.0A resolution. The structure shows the characteristic P450 fold as seen in other members of the family, with the lengths and orientations of the individual secondary structural elements being very similar to those seen in 2C9. There are, however, several important differences, the most notable involving the F helix, the F-G loop, the B'helix, beta sheet 4, and part of beta sheet 1, all of which are situated on the distal face of the protein. The 2D6 structure has a well defined active site cavity above the heme group, containing many important residues that have been implicated in substrate recognition and binding, including Asp-301, Glu-216, Phe-483, and Phe-120. The crystal structure helps to explain how Asp-301, Glu-216, and Phe-483 can act as substrate binding residues and suggests that the role of Phe-120 is to control the orientation of the aromatic ring found in most substrates with respect to the heme. The structure has been compared with published homology models and has been used to explain much of the reported site-directed mutagenesis data and help understand the metabolism of several compounds.

Fibroblast activation protein alpha (FAPalpha) is highly expressed in epithelial cancers and has been implicated in extracellular matrix remodeling, tumor growth, and metastasis. We present the first high resolution structure for the apoenzyme as well as kinetic data toward small dipeptide substrates. FAPalpha exhibits a dipeptidyl peptidase IV (DPPIV)-like fold, featuring an alpha/beta-hydrolase domain and an eight-bladed beta-propeller domain. Known DPPIV dipeptides are cleaved by FAPalpha with an approximately 100-fold decrease in catalytic efficiency compared with DPPIV. Moreover, FAPalpha, but not DPPIV, possesses endopeptidase activity toward N-terminal benzyloxycarbonyl (Z)-blocked peptides. Comparison of the crystal structures of FAPalpha and DPPIV revealed one major difference in the vicinity of the Glu motif (Glu(203)-Glu(204) for FAPalpha; Glu(205)-Glu(206) for DPPIV) within the active site of the enzyme. Ala(657) in FAPalpha, instead of Asp(663) as in DP-PIV, reduces the acidity in this pocket, and this change could explain the lower affinity for N-terminal amines by FAPalpha. This hypothesis was tested by kinetic analysis of the mutant FAPalpha/A657D, which shows on average an approximately 60-fold increase in the catalytic efficiency, as measured by k(cat)/K(m), for the cleavage of dipeptide substrates. Furthermore, the catalytic efficiency of the mutant is reduced by approximately 350-fold for cleavage of Z-Gly-Pro-7-amino-4-methylcoumarin. Our data provide a clear understanding of the molecular determinants responsible for the substrate specificity and endopeptidase activity of FAPalpha.