Effect of management structure and organisational process on decisions in industrial design

This thesis is divided into three sections. Section 1 provides the background and historical context for the study. Section 2 consists of four chapters presenting the research project and its findings, and Section 3 contains of two concluding chapters. This thesis considers the structure and organisational processes surrounding industrial design in manufacturing and service industries in Britain, and identifies and categorises the many decisions taken by managers that directly impact upon design development. The thesis differentiates between the acknowledged decision-making of designers and the unacknowledged decision-making of non-designers. These are called respectively "seen" and "silent" design, and the thesis concludes that design development is at its most effective when these processes act in tandem. Many organisations suffer from a corrupted process of design which at worst prevents new product development and at best slows and complicates it. In many cases this appears to be associated with a failure to give voice to the silent design activities of managers. The thesis uses primary data from representative case studies to trace the design process in organisations which can be shown to have used design "well" or "badly". The first step in this process is to understand the origins of any mistakes made in the categorisation of design. The second step is to recognise the way in which design, defined as a planning process to put ideas into action, has or has not been integral to new product development. The third step is to identify to what extent, at each stage of the process, there has been effective use of the deep knowledge vested in management and workforce. This deep, or "tacit" knowledge is also related to the idea of core competencies. The thesis suggests that utilisation of the deep knowledge in an organisation, changing it from passive to active, becomes sustainable as the two design processes are re-integrated in design development

Elaboration de nouveaux procédés de synthèse et caractérisation de talcs sub-microniques : de la recherche fondamentale vers des applications industrielles

Cette thèse s'inscrit dans le processus général d'innovation dans le domaine des matériaux composites. Financée par le projet ANR NANOTALC, elle a permis de réaliser des avancées considérables dans la procédure de production de nouvelles nanocharges minérales de type talc. Le procédé de synthèse du talc a été revisité dans le but de le rendre compatible avec des exigences industrielles en termes de rendement et d'efficacité. Ce procédé supplante les précédents en ce qu'il permet l'obtention d'un produit 100% talc avec un gain de temps et un gain de cristallinité tout en respectant quelques principes de la chimie verte. La caractérisation cristallochimique du nouveau talc synthétique a permis l'obtention de nouvelles signatures spectrales liées aux dimensions submicroniques, qui permettent par ailleurs de comprendre désormais certains comportements énigmatiques de poudres naturelles. Le talc synthétique issu de ce nouveau procédé se distingue de son homologue naturel par sa taille submicronique, sa pureté chimique et minérale mais aussi par son caractère hydrophile, caractère amplifié par l'abondance de bordures latérales porteuses de fonction silanols. Cette thèse retrace aussi les différentes techniques testées pour optimiser ce procédé et propose une nouvelle solution technique pour transposer la synthèse à une échelle semi-industrielle.This thesis takes part of the general process of innovation in the domain of composite materials. The funding by the ANR NANOTALC project allowed significant progress in the process of production of new talc-like mineral nanofillers. The talc synthesis process has been revised in order to achieve compatibility with industrial requirements in terms of performance and efficiency. This new process replaces the previous ones since it saves time, leads to a 100% talc product having a high crystallinity, in the respect of few principles of the green chemistry. The crystal-chemistry characterization of the new synthetic talc shows new spectral signatures related to nanoscale dimensions, which allow also understanding of some until now unexplained behavior of natural powders. The synthetic talc derived from this new process differs from its natural counterpart in its submicron size, its chemical and mineral purity and also in its hydrophilic character, which is enhanced by the abundance of particle edges bearing silanol functions. This thesis also describes the various techniques tested to optimize this process and provides a new technical solution for the implementation of the synthesis on a semi-industrial scale

Predictors of Engagement in a Parenting Intervention Designed to Prevent Child Maltreatment

Objective: The objectives of this analysis were to: 1) assess the impact of sociodemographic factors, and perceived costs and benefits on engagement in a parenting program designed to prevent child maltreatment, 2) determine if perceived costs and benefits mediated the association between sociodemographic factors and engagement, and 3) assess whether or not race/ethnicity moderated the relationship between sociodemographic factors, perceived costs and benefits, and engagement.Methods: Perceived costs and benefits of the intervention were assessed from parents providing self-reports, including satisfaction/ usefulness of the program (benefits), and time/difficulty associated with the program (costs). Engagement was defined as attendance at both the mid-point and then the number of visits attended throughout the remainder of the intervention. To investigate the direct and indirect effects (through perceived costs and benefits) of parental sociodemographic factors (education, age, gender, number of children, household income) on program engagement, data were analyzed with structural equation modeling (SEM). To assess the potential moderating effect of race/ethnicity, separate models were tested for White and African-American parents.Results: Perceived benefits positively impacted attendance for both White (n=227) and African-American (n=141) parents, whereas perceived costs negatively influenced attendance only for White parents. Parent education and age directly impacted attendance for White parents, but no sociodemographic factor directly impacted attendance for African-American parents. The indirect impact of sociodemographic characteristics on attendance through perceived costs and perceived benefits differed by race/ethnicity.Conclusions: Results suggest that White parents participate in a parenting program designed to prevent child maltreatment differently based upon their perceived benefits and costs of the program, and based on benefits only for African-American parents. Parental perception of costs and/or benefits of a program may threaten the effectiveness of interventions to prevent child maltreatment for certain racial/ethnic groups, as it keeps them from fully engaging in empirically validated programs. Different methods may be required to retain participation in violence prevention programs depending upon race/ethnicity

Pre‐screening models for patient engagement: The MOPEAD project

AbstractBackgroundAlzheimer's disease (AD) is a devastating condition that not only impacts greatly on the patient's health but also poses an important burden on the patient's immediate family circle. Early detection of AD allows patients to have an active role in managing their condition, and to plan how to minimize the strain on their dear ones. Despite known benefits, a large proportion of dementia cases remains undiagnosed or receives a late stage diagnosis. The MOPEAD project aims to address this issue by exploring innovative strategies to emerge "hidden" cases of cognitive impairment.MethodMemory clinics located in five different European countries participated in the project. Four innovative pre‐screening strategies were implemented to detect cognitive decline among individuals aged 65‐85 years who had never received a dementia related diagnosis: a) a web‐based pre‐screening tool along with an online marketing campaign, b) open house initiatives where people with memory complaints were invited to receive a quick evaluation at participating memory clinics, c) a primary care‐based protocol for early detection of cognitive decline using easily administered tools, and d) a tertiary care‐based pre‐screening at diabetologist clinics specifically designed to assess risk of dementia among patients with diabetes. A positive pre‐screening result implied that individuals were at high risk of having mild cognitive impairment or AD.ResultThe number of individuals enrolled, and the proportion of those with positive pre‐screening results varied across strategies. The web‐based tool evaluated the largest number of individuals (n=1487) and yielded 547 positive results (36.8%). The Open house initiative pre‐screened 661 subjects of whom 235 (35.6%) obtained a positive result. A total of 435 patients were pre‐screened in the primary care‐based strategy and 193 of them (44.4%) were found to have a positive result. Finally, 264 patients from diabetes clinics underwent pre‐screening and 154 (58.3%) showed a positive result.ConclusionUsing innovative pre‐screening strategies, we were able to identify 1129 individuals at high risk of having dementia who had otherwise remained unnoticed. Initiatives like this, show us the way to go in order to shift the paradigm of AD towards an earlier diagnosis

Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin

Variation in cellular gene expression levels has been shown to be inherited. Expression is controlled at transcriptional and post-transcriptional levels. Internal ribosome entry sites (IRES) are used by viruses to bypass inhibition of cap-dependent translation, and by eukaryotic cells to control translation under conditions when protein synthesis is inhibited. We aimed at identifying genomic determinants of variability in IRES-mediated translation of viral [Encephalomyocarditis virus (EMCV)] and cellular IRES [X-linked inhibitor-of-apoptosis (XIAP) and c-myc]. Bicistronic lentiviral constructs expressing two fluorescent reporters were used to transduce laboratory and B lymphoblastoid cell lines [15 CEPH pedigrees (n = 205) and 50 unrelated individuals]. IRES efficiency varied according to cell type and among individuals. Control of IRES activity has a significant genetic component (h2 of 0.47 and 0.36 for EMCV and XIAP, respectively). Quantitative linkage analysis identified a suggestive locus (LOD 2.35) on chromosome 18q21.2, and genome-wide association analysis revealed of a cluster of SNPs on chromosome 3, intronic to the FHIT gene, marginally associated (P = 5.9E-7) with XIAP IRES function. This study illustrates the in vitro generation of intermediate phenotypes by using cell lines for the evaluation of genetic determinants of control of elements such as IRES

IL-1-induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation

The features that define autoreactive T helper (Th) cell pathogenicity remain obscure. We have previously shown that Th cells require the transcription factor Bhlhe40 to mediate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Here, using Bhlhe40 reporter mice and analyzing both polyclonal and TCR transgenic Th cells, we found that Bhlhe40 expression was heterogeneous after EAE induction, with Bhlhe40-expressing cells displaying marked production of IFN-γ, IL-17A, and granulocyte-macrophage colony-stimulating factor. In adoptive transfer EAE models, Bhlhe40-deficient Th1 and Th17 cells were both nonencephalitogenic. Pertussis toxin (PTX), a classical co-adjuvant for actively induced EAE, promoted IL-1β production by myeloid cells in the draining lymph node and served as a strong stimulus for Bhlhe40 expression in Th cells. Furthermore, PTX co-adjuvanticity was Bhlhe40 dependent. IL-1β induced Bhlhe40 expression in polarized Th17 cells, and Bhlhe40-expressing cells exhibited an encephalitogenic transcriptional signature. In vivo, IL-1R signaling was required for full Bhlhe40 expression by Th cells after immunization. Overall, we demonstrate that Bhlhe40 expression identifies encephalitogenic Th cells and defines a PTX–IL-1–Bhlhe40 pathway active in EAE

Body Fat Free Mass Is Associated with the Serum Metabolite Profile in a Population-Based Study

To characterise the influence of the fat free mass on the metabolite profile in serum samples from participants of the population-based KORA (Cooperative Health Research in the Region of Augsburg) S4 study. Analyses were based on metabolite profile from 965 participants of the S4 and 890 weight-stable subjects of its seven-year follow-up study (KORA F4). 190 different serum metabolites were quantified in a targeted approach including amino acids, acylcarnitines, phosphatidylcholines (PCs), sphingomyelins and hexose. Associations between metabolite concentrations and the fat free mass index (FFMI) were analysed using adjusted linear regression models. To draw conclusions on enzymatic reactions, intra-metabolite class ratios were explored. Pairwise relationships among metabolites were investigated and illustrated by means of Gaussian graphical models (GGMs). We found 339 significant associations between FFMI and various metabolites in KORA S4. Among the most prominent associations (p-values 4.75 × 10(-16)-8.95 × 10(-06)) with higher FFMI were increasing concentrations of the branched chained amino acids (BCAAs), ratios of BCAAs to glucogenic amino acids, and carnitine concentrations. For various PCs, a decrease in chain length or in saturation of the fatty acid moieties could be observed with increasing FFMI, as well as an overall shift from acyl-alkyl PCs to diacyl PCs. These findings were reproduced in KORA F4. The established GGMs supported the regression results and provided a comprehensive picture of the relationships between metabolites. In a sub-analysis, most of the discovered associations did not exist in obese subjects in contrast to non-obese subjects, possibly indicating derangements in skeletal muscle metabolism. A set of serum metabolites strongly associated with FFMI was identified and a network explaining the relationships among metabolites was established. These results offer a novel and more complete picture of the FFMI effects on serum metabolites in a data-driven network

Phasic-to-tonic shift in trunk muscle activity relative to walking during low-impact weight bearing exercise

The aim of this study was to investigate the influence of an exercise device, designed to improve the function of lumbopelvic muscles via low-impact weight-bearing exercise, on electromyographic (EMG) activity of lumbopelvic, including abdominal muscles. Surface EMG activity was collected from lumbar multifidus (LM), erector spinae (ES), internal oblique (IO), external oblique (EO) and rectus abdominis (RA) during overground walking (OW) and exercise device (EX) conditions. During walking, most muscles showed peaks in activity which were not seen during EX. Spinal extensors (LM, ES) were more active in EX. Internal oblique and RA were less active in EX. In EX, LM and ES were active for longer than during OW. Conversely, EO and RA were active for a shorter duration in EX than OW. The exercise device showed a phasic-to-tonic shift in activation of both local and global lumbopelvic muscles and promoted increased activation of spinal extensors in relation to walking. These features could make the exercise device a useful rehabilitative tool for populations with lumbopelvic muscle atrophy and dysfunction, including those recovering from deconditioning due to long-term bed rest and microgravity in astronauts

EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis

Objective To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). Methods An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A–D: A typically consistent level 1 studies and D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0–10: 0 completely disagree and 10 completely agree) of the PtCs were determined by the Task Force members. Results Two overarching principles and 11 PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and non-pharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to level D. The mean LoA with the overarching principles and PtCs was generally high (8.4–9.6). Conclusions These PtCs for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council