Developing a Conceptual Design Engineering Toolbox and its Tools

In order to develop a successful product, a design engineer needs to pay attention to all relevant aspects of that product. Many tools are available, software, books, websites, and commercial services. To unlock these potentially useful sources of knowledge, we are developing C-DET, a toolbox for conceptual design engineering. The idea of C-DET is that designers are supported by a system that provides them with a knowledge portal on one hand, and a system to store their current work on the other. The knowledge portal is to help the designer to find the most appropriate sites, experts, tools etc. at a short notice. Such a toolbox offers opportunities to incorporate extra functionalities to support the design engineering work. One of these functionalities could be to help the designer to reach a balanced comprehension in his work. Furthermore C-DET enables researchers in the area of design engineering and design engineers themselves to find each other or their work earlier and more easily. Newly developed design tools that can be used by design engineers but have not yet been developed up to a commercial level could be linked to by C-DET. In this way these tools can be evaluated in an early stage by design engineers who would like to use them. This paper describes the first prototypes of C-DET, an example of the development of a design tool that enables designers to forecast the use process and an example of the future functionalities of C-DET such as balanced comprehension

Does Co-Creation of Service Recovery Create Value for Customers? The Underlying Mechanism of Motivation and the Role of Operant Resources

International audienceThis study focuses on the underlying mechanism that leads to co‐recovery behaviour and favourable co‐created value as response to a service failure. It argues that consumers’ ability to integrate their operant resources (e.g., knowledge and skills) to co‐recover from a service failure motivates them to express higher value co‐recovery in‐role behaviour and hence enjoy higher hedonic and utilitarian values. To test this claim, our study investigates the impact of consumers’ ability to co‐recover on value co‐recovery in‐role behaviour by taking into account extrinsic and intrinsic motivation as mediators. The results reveal that extrinsic motivation only partially mediates the relationship between ability to co‐recover and value co‐recovery in‐role behaviour. Furthermore, the outcomes demonstrate that value co‐recovery in‐role behaviour increases utilitarian value but decreases hedonic valu

Muscle biopsies in clinical trials for Duchenne muscular dystrophy - Patients' and caregivers' perspective

The number of clinical trials for Duchenne muscular dystrophy is increasing. Many trials require muscle biopsies, which involve an invasive surgical procedure. Little is known about short- and long-term impacts of muscle biopsies as perceived by patients and caregivers. Therefore a survey was held among patients and their caregivers who participated in trials involving muscle biopsies, in seven countries. Seventy-eight responses were received. Analysis revealed that many patients and parents had significant anxiety before the biopsy. The main concern of caregivers was the required general anaesthesia. In most cases biopsies caused pain and temporarily hampered daily activities. The main long-term impact was scarring, although large variation in size was reported. Seventy-nine percent of caregivers were little bothered and 21% were moderately or severely bothered by the scar. Willingness to consider another biopsy in future protocols was higher for open-label studies than for placebo-controlled trials. Caregivers stressed the importance of knowing the results of biopsy analyses; only a minority actually received this information. Recommendations are made on the informed consent procedure regarding risks and consequences of muscle biopsies, and communication of results. Furthermore, efforts should be made to minimise the impact of biopsies through pain management and by considering plastic surgery

Guidance in social and ethical issues related to clinical, diagnostic care and novel therapies for hereditary neuromuscular rare diseases: "translating" the translational.

Drug trials in children engage with many ethical issues, from drug-related safety concerns to communication with patients and parents, and recruitment and informed consent procedures. This paper addresses the field of neuromuscular disorders where the possibility of genetic, mutation-specific treatments, has added new complexity. Not only must trial design address issues of equity of access, but researchers must also think through the implications of adopting a personalised medicine approach, which requires a precise molecular diagnosis, in addition to other implications of developing orphan drugs. It is against this background of change and complexity that the Project Ethics Council (PEC) was established within the TREAT-NMD EU Network of Excellence. The PEC is a high level advisory group that draws upon the expertise of its interdisciplinary membership which includes clinicians, lawyers, scientists, parents, representatives of patient organisations, social scientists and ethicists. In this paper we describe the establishment and terms of reference of the PEC, give an indication of the range and depth of its work and provide some analysis of the kinds of complex questions encountered. The paper describes how the PEC has responded to substantive ethical issues raised within the TREAT-NMD consortium and how it has provided a wider resource for any concerned parent, patient, or clinician to ask a question of ethical concern. Issues raised range from science related ethical issues, issues related to hereditary neuromuscular diseases and the new therapeutic approaches and questions concerning patients rights in the context of patient registries and bio-banks. We conclude by recommending the PEC as a model for similar research contexts in rare diseases

Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels compared to protease inhibitor-based therapy

Background: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Methods: CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART. Results: In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (padj = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (padj = 0.048 and padj = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals. Conclusions: All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size

Nose to Tail: Using the Whole Employment Relationship to Link Worker Participation to Operational Performance

Although many employers continue to adopt various forms of worker participation or employee involvement, expected positive gains often fail to materialize. One explanation for the weak or altogether missing performance effects is that researchers rely on frameworks that focus almost exclusively on contingencies related to the workers themselves or to the set of tasks subject to participatory processes. This study is premised on the notion that a broader examination of the employment relationship within which a worker participation program is embedded reveals a wider array of factors impinging upon its success. I integrate labor relations theory into existing insights from the strategic human resource management literature to advance an alternative framework that additionally accounts for structures and processes above the workplace level — namely, the (potentially implicit) contract linking employees to the organization and the business strategies enacted by the latter. The resulting propositions suggest that the performance-enhancing impact of worker participation hinges on the presence of participatory or participation-supporting structures at all three levels of the employment relationship. I conclude with implications for participation research

Moving beyond the 2018 minimum international care considerations for osteoporosis management in duchenne muscular dystrophy (DMD): Meeting report from the 3rd International Muscle-Bone Interactions Meeting 7th and 14th November 2022

This current manuscript summarizes the proceedings of the “Third Muscle-bone interactions in Duchenne Muscular Dystrophy Symposium: Moving Beyond the 2018 Minimum International Standards of Care for Osteoporosis Management”, an event co-organized by the World Duchenne Organization (www.worldduchenne.org) and the International Conference on Children’s Bone Health (www.theiscbh.org). This virtual symposium, held on November 7th and 14th 2022, brought together a total of 385 delegates representing 55 countries registered for the symposium, which included 239 clinicians, 70 researchers, 40 patient representatives and others from pharmaceutical companies and regulators. This symposium aimed to review the evidence base that informed the 2018 international minimum Care Considerations, best practices for implementation of these Care Considerations, and emerging knowledge that has arisen from research since the 2018 Care Considerations that shines light on the path forward. The online symposium and this report cover the following areas: 1. Current understanding of the bone morbidity in DMD, especially in relation to conventional glucocorticoid therapy. 2. The published, 2018 minimum international Care Considerations for osteoporosis monitoring and management in DMD. 3. Real world initiatives and challenges in the implementation of the 2018 minimum international Care Considerations for osteoporosis monitoring and management in DMD. 4. The need to consider strategies to move beyond the 2018 minimum international Care Considerations to prevent first fractures in DMD. 5. New therapies in DMD with potential impact on skeletal outcomes