Addressing the gap between manufacturers’ sustainability intentions and effective sustainable product development : the big themes framework

Sustainability is a complex concept with various meanings and operationalizations. Consequently, manufacturers face difficulties to set appropriate strategies and goals for sustainable product design (SPD), even though intentions to make more sustainable products are stronger than ever before. This paper investigates a framework of themes in sustainability, i.e., Big Themes, which product developers can use to find and select appropriate sustainability strategies and goals. The Big Themes framework is made in the context of a research consortium of six manufacturing companies. An analysis of CSR reports of manufacturers operating in related industries forms the basis of the framework under investigation

Fuzzy sustainability incentives in new product development : an empirical exploration of sustainability challenges in manufacturing companies

Purpose - This paper investigates the challenges encountered by manufacturing companies in managing sustainability in new product development (NPD). It describes six case studies of manufacturers aiming for sustainability improvements but experiencing difficulties in implementing them. Design/methodology/approach - The paper starts with a literature study. Academic literature offers explanations as to why manufacturers want to implement sustainability in NPD, and suggests methods for such implementations. This paper employs the systems theory of control to build a research framework for analyzing the challenges. Empirical data are gathered through workshops and interviews with NPD managers in the case companies .\u3cbr/\u3eFindings - In-depth analyses have provided three insights. First, the study shows that sustainability pressures and incentives in a firm’s contexts can be fuzzy or even absent. The fuzziness of sustainability incentives is often neglected in the literature on sustainability and NPD. Secondly, the case companies face difficulties when setting the scope, goals, and ambitions that effectively direct NPD decisions and efforts toward designing sustainable products. Thirdly, the results show that deploying sustainability methods, tools, and metrics, such as a LifeCycle Assessment (LCA) or Design for Environment (DfE), are not sufficient to achieve sustainability in NPD. These findings call for research on sustainability and NPD processes in contexts where sustainability incentives and needs are fuzzy so as to acquire insights applicable to sustainable product development management that is proactive rather than reactive.\u3cbr/\u3eOriginality/value - Instead of focusing only on the output of sustainable products, this paper presents a more nuanced perspective on managing sustainability in NPD. Moreover, by adopting the holistic perspective of the systems theory of control, we challenge the assumption that there are already sufficient external incentives to force companies toward greater sustainability. Consequently, in the light of proactive sustainability management, we recommend three tracks for further research: organization and filtering of information concerning sustainability pressures and incentives in a firm’s context; and how to manage sustainability proactively rather than reactively

An Integrated Population Pharmacokinetic Meta-Analysis of Propofol in Morbidly Obese and Nonobese Adults, Adolescents, and Children

This study describes a population pharmacokinetic meta-analysis of propofol to characterize the influence of body size measures and age in morbidly obese and nonobese adults, adolescents, and children. Sixty morbidly obese and nonobese adult patients (55–167 kg; 21–79 years) and 34 morbidly obese and nonobese adolescents and children (37–184 kg; 9–20 years) were included. The results show that clearance increased with total body weight in an allometric function while age was found to influence clearance in a bilinear fashion with two distinct slopes, reflecting an initial increase and subsequent decrease as a result of aging. Using these two functions, the influence of both (over)weight and age on propofol clearance was well characterized, which may provide a basis for dosing across this diverse group of patients

Full regeneration of segmental bone defects using porous titanium implants loaded with BMP-2 containing fibrin gels

Regeneration of load-bearing segmental bone defects is a major challenge in trauma and orthopaedic surgery. The ideal bone graft substitute is a biomaterial that provides immediate mechanical stability, while stimulating bone regeneration to completely bridge defects over a short period. Therefore, selective laser melted porous titanium, designed and fine-tuned to tolerate full load-bearing, was filled with a physiologically concentrated fibrin gel loaded with bone morphogenetic protein-2 (BMP-2). This biomaterial was used to graft critical-sized segmental femoral bone defects in rats. As a control, porous titanium implants were either left empty or filled with a fibrin gels without BMP-2. We evaluated bone regeneration, bone quality and mechanical strength of grafted femora using in vivo and ex vivo µCT scanning, histology, and torsion testing. This biomaterial completely regenerated and bridged the critical-sized bone defects within eight weeks. After twelve weeks, femora were anatomically re-shaped and revealed open medullary cavities. More importantly, new bone was formed throughout the entire porous titanium implants and grafted femora regained more than their innate mechanical stability: torsional strength exceeded twice their original strength. In conclusion, combining porous titanium implants with a physiologically concentrated fibrin gels loaded with BMP-2 improved bone regeneration in load-bearing segmental defects. This material combination now awaits its evaluation in larger animal models to show its suitability for grafting load-bearing defects in trauma and orthopaedic surgery

Full regeneration of segmental bone defects using porous titanium implants loaded with BMP-2 containing fibrin gels

Regeneration of load-bearing segmental bone defects is a major challenge in trauma and orthopaedic surgery. The ideal bone graft substitute is a biomaterial that provides immediate mechanical stability, while stimulating bone regeneration to completely bridge defects over a short period. Therefore, selective laser melted porous titanium, designed and fine-tuned to tolerate full load-bearing, was filled with a physiologically concentrated fibrin gel loaded with bone morphogenetic protein-2 (BMP-2). This biomaterial was used to graft critical-sized segmental femoral bone defects in rats. As a control, porous titanium implants were either left empty or filled with a fibrin gels without BMP-2. We evaluated bone regeneration, bone quality and mechanical strength of grafted femora using in vivo and ex vivo ?CT scanning, histology, and torsion testing. This biomaterial completely regenerated and bridged the critical-sized bone defects within eight weeks. After twelve weeks, femora were anatomically re-shaped and revealed open medullary cavities. More importantly, new bone was formed throughout the entire porous titanium implants and grafted femora regained more than their innate mechanical stability: torsional strength exceeded twice their original strength. In conclusion, combining porous titanium implants with a physiologically concentrated fibrin gels loaded with BMP-2 improved bone regeneration in load-bearing segmental defects. This material combination now awaits its evaluation in larger animal models to show its suitability for grafting loadbearing defects in trauma and orthopaedic surgery.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin

The regulation of interleukin-8 by hypoxia in human macrophages--a potential role in the pathogenesis of the acute respiratory distress syndrome (ARDS).

BACKGROUND: The acute respiratory distress syndrome (ARDS) represents a form of severe acute inflammatory lung disease. We have previously demonstrated significantly raised interleukin-8 (IL-8) levels in the lungs of at-risk patients that progress to ARDS, and identified the alveolar macrophage as an important source of this chemokine. We wished to extend this study in a well-defined group of patients with major trauma, and to investigate potential mechanisms for rapid intrapulmonary IL-8 generation. MATERIALS AND METHODS: Patients with major trauma underwent bronchoalveolar lavage (BAL) and IL-8 levels were measured in BAL fluid by ELISA. Human macrophages were derived from peripheral blood monocytes from healthy volunteers. Rabbit alveolar macrophages were obtained from ex-vivo lavage of healthy rabbit lungs. Macrophages were culture under normoxic or hypoxic (PO2 26 mmHg) conditions. IL-8 and other proinflammatory mediator expression was measured by ELISA, northern blotting or multi-probe RNase protection assay. RESULTS: In patients with major trauma, IL-8 levels were significantly higher in patients that progressed to ARDS compared to those that did not (n = 56, P = 0.0001). High IL-8 levels negatively correlated with PaO2/FiO2 (r = -0.56, P < 0.001). In human monocyte derived macrophages hypoxia rapidly upregulated IL-8 protein (within 2 hours) and mRNA expression (within 30 mins). Acute hypoxia also increased rabbit alveolar macrophage IL-8 expression. Hypoxia increased DNA binding activity of AP-1 and C/EBP but not NF-kappaB. Hypoxia induced HIF-1 expression, but cobaltous ions and desferrioxamine did not mimic hypoxic IL-8 induction. Hypoxia downregulated a range of other proinflammatory mediators, including MCP-1 and TNF-alpha. Both the pattern of cytokine expression and transcription factor activation by hypoxia was different to that seen with endotoxin. CONCLUSIONS: Rapidly raised intrapulmonary IL-8 levels are associated with ARDS progression in patients with major trauma. Acute hypoxia, a clinically relevant stimulus, rapidly and selectively upregulates IL-8 in macrophages associated with a novel pattern of transcription factor activation. Acute hypoxia may represent one of potentially several proinflammatory stimuli responsible for rapid intrapulmonary IL-8 generation in patients at-risk of ARDS

Chemokine signalling: pivoting around multiple phosphoinositide 3-kinases

The role of chemokines in mediating directional cell migration is well established, but more recently it has become evident that chemokines are able to couple to distinct signalling pathways that are involved in not only chemotaxis, but also cell growth and transcriptional activation. The signalling pathway controlled by the phosphoinositide 3-kinase (PI3K) family of lipid kinases has been the focus of much attention with respect to their role in chemokine-mediated functional responses. Indeed, there now exists convincing biochemical, pharmacological and genetic evidence that both CC and CXC chemokines stimulate PI3K-dependent chemotaxis of inflammatory cells such as eosinophils, macrophages, neutrophils and T lymphocytes. This review considers the role of individual PI3Ks (e.g. the p85/p110 heterodimer, PI3Kγ and PI3KC2α) as well their downstream effector targets in mediating chemokine-stimulated cell migration