Rapid manufacturing as a tool for agile manufacturing: applications and implementation perspectives

Manufacturing engineers and technologists around the globe are already well familiar with manufacturing methodologies and systems developments in the last part of the twentieth century. Many are probably also familiar with the current state of Rapid Prototyping (RP) technologies, especially in the areas of concept model making and prototype development. They may not however, be so familiar with the more recent developments of these technologies towards Rapid Manufacturing (RM) and the directions which the applications of RM technologies are taking for agile manufacturing purposes in particular. This paper critically reviews the various technologies currently available, outlines development trends in RM, discusses the approach, application and implementation perspectives by which these RM technologies are applied for increasing agility and responsiveness in manufacturing. Furthermore, the paper describes two case study examples to further illustrate the application scenarios in agile manufacturing before concluding remarks

Extending the product portfolio with ‘devolved manufacturing’: Methodology and case studies

Current research by the developers of rapid prototyping systems is generally focused on improvements in cost, speed and materials to create truly economic and practical economic rapid manufacturing machines. In addition to being potentially smarter/faster/cheaper replacements for existing manufacturing technologies, the next generation of these machines will provide opportunities not only for the design and fabrication of products without traditional constraints, but also for organizing manufacturing activities in new, innovative and previously undreamt of ways. This paper outlines a novel devolved manufacturing (DM) ‘factory-less’ approach to e-manufacturing, which integrates Mass Customization (MC) concepts, Rapid Manufacturing (RM) technologies and the communication opportunities of the Internet/WWW, describes two case studies of different DM implementations and discusses the limitations and appropriateness of each, and finally, draws some conclusions about the technical, manufacturing and business challenges involved

Supply chain implications of sustainable design strategies for electronics products

Increasing legislative and consumer pressures on manufacturers to improve sustainability necessitates that manufacturers consider the overall life cycle and not be scope restricted in creating products. Product strategies to improve sustainability have design implications as many of the decisions made during the design stage will then determine the environmental performance of the final product. Coordination across the supply chain is potentially beneficial as products with improved energy efficiency can be better realised. This paper examines traditional product provision and proposes a sustainable product design process using life cycle assessment (LCA) at key points, as these decision points can provide opportunities for environmental improvements of products. Case studies of consumer and industry products in the electronics sector are examined in terms of improving sustainability by reviewing product architecture and technology solutions. This paper proposes methods and analytical models to better understand sustainable design strategies for manufacturing firms and thus aid manufacturers during the earliest stages of product planning to consider alternative product development approaches which are more sustainable

Sustainable development strategies for product provision and manufacturing approaches

Manufacturing firms are under many pressures both financially and competitive which focus attention on the performance of their manufacturing processes. In this paper the opportunities for improving the environmental impact of products within the constraints of existing manufacturing infrastructure are examined. Approaches which support sustainability in two aspects are proposed, firstly, the provision of products to the users in ways which extend the product life and secondly, manufacturing approaches which reduce resource usage. The provision and manufacture of products in ways that are truly sustainable are inhibited by three issues: firstly, decisions are predominantly made solely from the perspective of the “vendor” (and do not consider the wider perspective); secondly, that generally the scope of business planning is still rooted in production/manufacturing costs (and not consumption costs) and thirdly, the current performance measures (e.g. KPIs) mainly focus on profitability. The rationale for this conference paper is the argument that there is a need to raise the awareness during the earliest stages of business planning that there may be alternative approaches which are more sustainable. The concepts presented here will underpin further research into performance measures which encompass sustainability and resulting business planning implications

The case for low-level BACE1 inhibition for the prevention of Alzheimer disease

Alzheimer disease (AD) is the most common cause of dementia in older individuals (>65 years) and has a long presymptomatic phase. Preventive therapies for AD are not yet available, and potential disease-modifying therapies targeting amyloid-β plaques in symptomatic stages of AD have only just been approved in the United States. Small-molecule inhibitors of β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1; also known as β-secretase 1) reduce the production of amyloid-β peptide and are among the most advanced drug candidates for AD. However, to date all phase II and phase III clinical trials of BACE inhibitors were either concluded without benefit or discontinued owing to futility or the occurrence of adverse effects. Adverse effects included early, mild cognitive impairment that was associated with all but one inhibitor; preliminary results suggest that the cognitive effects are non-progressive and reversible. These discontinuations have raised questions regarding the suitability of BACE1 as a drug target for AD. In this Perspective, we discuss the status of BACE inhibitors and suggest ways in which the results of the discontinued trials can inform the development of future clinical trials of BACE inhibitors and related secretase modulators as preventative therapies. We also propose a series of experiments that should be performed to inform ‘go–no-go’ decisions in future trials with BACE inhibitors and consider the possibility that low levels of BACE1 inhibition could avoid adverse effects while achieving efficacy for AD prevention

A survey of attitudes toward clinical trials and genetic disclosure in autosomal dominant Alzheimer's disease

Introduction: Because of its genetic underpinnings and consistent age of onset within families, autosomal dominant Alzheimer's disease (ADAD) provides a unique opportunity to conduct clinical trials of investigational agents as preventative or symptom-delaying treatments. The design of such trials may be complicated by low rates of genetic testing and disclosure among persons at risk of inheriting disease-causing mutations. Methods: To better understand the attitudes toward genetic testing and clinical trials of persons at risk for ADAD, we surveyed participants in the Dominantly Inherited Alzheimer's Network (DIAN), a multisite longitudinal study of clinical and biomarker outcomes in ADAD that does not require learning genetic status to participate. Results: Eighty participants completed a brief anonymous survey by mail or on-line; 40 % reported knowing if they carried a gene mutation, 15 % did not know but expressed a desire to learn their genetic status, and 45 % did not know and did not desire to know their genetic status. Among participants who knew or wished to know their genetic status, 86 % were interested in participating in a clinical trial. Seventy-two percent of participants who did not wish to learn their genetic status reported that they would change their mind, if learning that they carried a mutation gave them the opportunity to participate in a clinical trial. Nearly all participants responded that they would be interested if an open-label extension were offered. Conclusions: These results suggest that the availability of clinical trials to prevent ADAD can affect persons' desire to undergo genetic testing and that consideration can be given to performing studies in which such testing is required

Tau accumulation in autosomal dominant Alzheimer’s disease: a longitudinal [18F]flortaucipir study

Cortical tau accumulation is a key pathological event that partly defines Alzheimer’s disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir (FTP) PET, MRI and clinical assessments; 26 individuals had more than one FTP PET scan. Standardised uptake value ratios (SUVRs) in prespecified regions of interest (ROIs) were obtained using inferior cerebellar grey matter as the reference region. We compared the changes in FTP SUVRs between presymptomatic carriers, symptomatic carriers and non-carriers, adjusting for age, sex and study site. We also investigated the relationship between regional FTP SUVRs and estimated years to/from symptom onset (EYO). Compared to both non-carriers and presymptomatic carriers, FTP SUVRs were significantly higher in symptomatic carriers in all ROIs tested (p 0.05), although increased FTP signal uptake was seen posteriorly in some individuals around the time of expected symptom onset. When we examined the relationship of FTP SUVR with respect to EYO, the earliest significant regional difference between mutation carriers and non-carriers was detected within the precuneus prior to estimated symptom onset in some cases. This study supports preliminary studies suggesting that presymptomatic tau tracer uptake is rare in ADAD. In cases where early uptake was seen, there was often a predilection for posterior regions (the precuneus and post-cingulate) as opposed to the medial temporal lobe, highlighting the importance of examining in vivo tau uptake beyond the confines of traditional Braak staging