Design characteristics of a workload manager to aid drivers in safety-critical situations

The objective of this study was to evaluate a workload manager designed to supervise the presentation of in-vehicle information for two age groups of drivers during safety-critical situations. The benefits of a workload manager were compared in various dual-task conditions involving a preceding or a concurrent in-vehicle alert during critical traffic situations. Objective measures such as drivers’ brake response times and secondary task response times as well as subjective measures of driver workload were used. Although older drivers performed worse in the dual task scenario with longer response times and poorer performance on the secondary task in comparison to the younger drivers, results indicated that both age groups benefited from the implementation of a workload manager. There was a consistent trend of improved driving and secondary task performance when the workload manager delayed non-critical information during safety-critical situations, indicating benefits for some otherwise distracted drivers. Implications for the design of a workload manager are discussed

The rise of inconspicuous consumption

Ever since Veblen and Simmel, luxury has been synonymous with conspicuous consumption. In this conceptual paper we demonstrate the rise of inconspicuous consumption via a wide-ranging synthesis of the literature. We attribute this rise to the signalling ability of traditional luxury goods being diluted, a preference for not standing out as ostentatious during times of economic hardship, and an increased desire for sophistication and subtlety in design in order to further distinguish oneself for a narrow group of peers. We decouple the constructs of luxury and conspicuousness, which allows us to reconceptualise the signalling quality of brands and the construct of luxury. This also has implications for understanding consumer behaviour practices such as counterfeiting and suggests that consumption trends in emerging markets may take a different path from the past

Stress Adaptation

We thank our numerous friends and colleagues for stimulating discussions about stress adaptation. We are also grateful to the following institutions for generously supporting our research. A.J.P.B was funded by the European Research Council (STRIFE, ERC-2009-AdG-249793), the UK Medical Research Council (MR/M026663/1 and MR/N006364/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), and the Wellcome Trust (080088; 097377). L.E.C. is supported by the Canadian Institutes of Health Research Operating Grants (MOP-86452 and MOP-119520), the Natural Sciences and Engineering Research Council (NSERC) of Canada Discovery Grants (06261 and 462167), an NSERC E.W.R. Steacie Memorial Fellowship (477598), a National Institutes of Health R01 Grant (R01AI120958), and a Canada Research Chair in Microbial Genomics and Infectious Disease. Work in the A.D.P. laboratory is funded by grants from the Spanish Ministerio de Innovación y Competitividad (BIO2013-47870-R), the European Commission (Marie Curie ITN FUNGIBRAIN; FP7-PEOPLE-ITN-607963), and the Junta de Andalucia (BIO296). J.Q. is funded by the UK Biotechnology and Biological Research Council (BB/K016939/1) and the Wellcome Trust (097377).Peer reviewedPostprin

The drivers of Corporate Social Responsibility in the supply chain. A case study.

Purpose: The paper studies the way in which a SME integrates CSR into its corporate strategy, the practices it puts in place and how its CSR strategies reflect on its suppliers and customers relations. Methodology/Research limitations: A qualitative case study methodology is used. The use of a single case study limits the generalizing capacity of these findings. Findings: The entrepreneur’s ethical beliefs and value system play a fundamental role in shaping sustainable corporate strategy. Furthermore, the type of competitive strategy selected based on innovation, quality and responsibility clearly emerges both in terms of well defined management procedures and supply chain relations as a whole aimed at involving partners in the process of sustainable innovation. Originality/value: The paper presents a SME that has devised an original innovative business model. The study pivots on the issues of innovation and eco-sustainability in a context of drivers for CRS and business ethics. These values are considered fundamental at International level; the United Nations has declared 2011 the “International Year of Forestry”

Investigating cardiac metabolism and the effect of novel metabolic modulation therapy on cardiac physiology and exercise capacity in aortic stenosis: a multi-parametric cardiac magnetic resonance study

Aortic stenosis is a major cause of morbidity and mortality in the western world. Whilst symptomatic patients with severe AS are treated with valve replacement surgery, there remains uncertainty about the best treatment for asymptomatic severe AS. Current guidelines recommend wait and watch strategy and offer surgery on occurrence of symptoms or evidence of systolic dysfunction. The annual rate of sudden cardiac death in asymptomatic severe AS remains close to 1%. Aortic disease is both a disease of the valve and myocardium. The valve mechanisms and structural LV changes secondary to pressure overload have been extensively studied before, but no medical therapy directed at the valve processes has so far shown beneficial effect on cardiac physiology or disease progression. Changes in cardiac metabolism in pressure overload hypertrophy seem to play an important role in pathophysiology of AS and transition to decompensation. The healthy human heart uses fatty acids as the main energy source ~70% of adenosine triphosphate (ATP) requirements. In AS, there is substrate shift with downregulation of fatty acid oxidation (FAO) and increased reliance on glycolysis, with evidence of myocardial lipid accumulation and impairment of myocardial energetics. Peroxisome proliferator activated receptor-alpha (PPAR-a) plays a central role in FAO signalling and controlling lipid homeostasis in the heart. Downregulation of this transcriptional factor is associated with the metabolic alterations and subsequent lipotoxicity in AS, which ultimately causes reduced ATP production and heart failure. However, it is unclear whether these metabolic changes have a cause or effect relationship with the two main pathological features of AS, left ventricular (LV) pressure loading and LV hypertrophy, and their relationship with myocardial fibrosis (which is commonly seen in AS), is unclear. Furthermore, it is yet unknown whether modulating cardiac metabolism would have any beneficial effect on disease progression or outcomes in AS. This thesis set out to establish the relationship between metabolic remodelling and cardiac structure and physiology in AS. It then evaluates the role of novel metabolic modulator therapy in asymptomatic moderate-severe AS. In Chapter 3 and 4, patients across the spectrum of AS were studied with advanced CMR imaging and phosphorus-31 magnetic resonance spectroscopy (31P-MRS) and cardiopulmonary exercise testing (CPET) respectively. It is demonstrated that metabolic changes, specifically myocardial lipid accumulation (steatosis) and impaired cardiac energetics appear to occur early in the disease process. In addition, whilst impairment in cardiac energetics is related to degree of LV hypertrophy, steatosis appears to be more related to the degree of LV pressure loading from valve obstruction. Furthermore, these patients despite being asymptomatic with normal LVEF have evidence of subclinical LV dysfunction which occurs early in the disease process. Moreover, these patients though able to exercise to volitional exhaustion without developing symptoms have reduced average peak VO2 and VE/VCO2, both of which are predictors of outcome in cardiac disease. In Chapter 4 and 5, the effect of the PPARa agonist Fenofibrate was evaluated on cardiac metabolism and physiology in a randomised double-blind placebo-controlled study. Fenofibrate reduced myocardial triglyceride content significantly after 6 months’ treatment with evidence of in vivo fatty acid oxidation upregulation. It also caused a modest improvement in cardiac energetics. However, this modulation did not show any measurable improvement in cardiac physiology or exercise capacity. Together, these data show that myocardial metabolic remodelling plays an important role in pathophysiology and progression of AS. The novel finding from this research is that metabolic changes occur early in the AS disease process and are associated with early subclinical systolic and diastolic dysfunction. This highlights that metabolic remodelling may play a causal role in disease progression. This research has also shown, for the first time, that metabolic alterations in AS are amenable to modulation with a PPARa agonist, with some improvement in cardiac physiology but the benefit of such modulation in advanced disease remains questionable. Whether targeting earlier disease would yield different results remains unanswered

Defining determinants of viral membrane protein immunogenicity

Acquired immunity to the delivery vector for in vivo gene transfer or expression applications limits therapy efficacy upon repeat vector administration. However, a controlled comparison of vector immunogenicity, comparing immune responses to different viral vectors at comparable doses through the same delivery route, is yet to be carried out. In this thesis, antibody assays were used to study the humoral response to repeat dosing of lentiviral (LV) vectors of variable pseudotype (Sendai Virus Fusion protein/Hemagglutinin Neuraminidase protein and Vesicular Stomatitis Virus glycoprotein). The effects of antigen dose and delivery method were assessed. Through this, the envelope:gag ratio was identified as an important determinant for vector immunogenicity. Upon the emergence of SARS-CoV-2 in the United Kingdom in early 2020, the focus of this thesis shifted to studying the human antibody response to this pandemic virus. Antibody assays previously used to study anti-vector pseudotype antibodies to gene transfer vectors were used to study the kinetics and magnitude of antibody responses to SARS-CoV-2 variants. Interestingly, SARSCoV-2 Spike (S) S2 domain-specific IgG antibodies, derived from previous heterotypic human coronavirus (HCoV) infection, were identified in individuals uninfected and unexposed to SARS-CoV-2, and these S2-specific cross-reactive antibodies showed neutralising activity to SARS-CoV-2 S-pseudotyped LV vectors in vitro with comparable efficacy to sera from COVID-19 patients. Sera from patients infected with SARS-CoV-2 variants D614G or Alpha were able to recognise and neutralise homotypic and heterotypic variant S proteins with variable efficacy. Surprisingly, in some cases, a reduction in efficacy of binding and neutralisation occurred in a unidirectional and asymmetric pattern. Together, this thesis explores the many factors which determine antibody induction and duration, and suggests ways in which we can use this information to design better therapeutics involving LV gene transfer, such as gene therapy and vaccination.Open Acces