Exploring customer trust and relationships in the online environment

This thesis presents eleven selected publications concerning trust and relationships in the online environment. The evolution of the research over ten years showcases the author’s dedication to the practical application of marketing for the benefit of organisations and individuals alongside contribution to academic knowledge. The advent of new technology by way of the internet has added a new dimension to the complexity of marketing strategy and, from a practical point of view, marketers need to incorporate cutting edge technology into their strategic thinking. Existing literature at the time that the author started this research was at the nascent stage and over the period of the research, it became obvious that technology could be used as a tool to help build relationships. Conversely, customers demonstrated varying degrees of trust in both the technologies and the organisations using online-based tools. It became essential, therefore, for organisations to appear trustworthy in order for customers to engage with online marketing platforms and subsequently entrust their purchasing activities to the online environment. The research appraised in this thesis makes a significant contribution to knowledge about marketing in the online environment and the implications of engendering consumer trust. Six key contributions to knowledge are claimed as a result of this work. Firstly, a framework for using online marketing strategically has been developed. Secondly, an analysis of how online marketing fits into the traditional marketing framework is provided. Thirdly, the author introduces the notion that trust in a brand influences online behaviour by reducing perceived risk, leading to consumers committing to online purchasing. Fourthly, online brand elements used to create credibility of a B2B brand are identified. Fifthly, the author presents an identification of how structural elements of websites can be utilized to differentiate online brands from competitors’ offerings. Finally, the author puts forward the proposition that marketers can learn from relatiaonships between contributors to online social networks. The researcher has utilised a variety of deliberately chosen methodologies, most of which are qualitative. The thesis also contains three secondary contributions related to research design. These are the use of a bought-in, permission-based email list, the innovative use of netnography to elicit rich data from online discussion forums and, finally, content analysis of websites. The work concludes by offering eight recommendations for future research directions

Understanding age-related modifications of motor control strategies

ISSN:1743-000

Ret function in muscle stem cells points to tyrosine kinase inhibitor therapy for facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) involves sporadic expression of DUX4, which inhibits myogenesis and is pro-apoptotic. To identify target genes, we over-expressed DUX4 in myoblasts and found that the receptor tyrosine kinase Ret was significantly up-regulated, suggesting a role in FSHD. RET is dynamically expressed during myogenic progression in mouse and human myoblasts. Constitutive expression of either RET9 or RET51 increased myoblast proliferation, whereas siRNA-mediated knockdown of Ret induced myogenic differentiation. Suppressing RET activity using Sunitinib, a clinically- approved tyrosine kinase inhibitor, rescued differentiation in both DUX4-expressing murine myoblasts and in FSHD patient-derived myoblasts. Importantly, Sunitinib also increased engraftment and differentiation of FSHD myoblasts in regenerating mouse muscle. Thus, DUX4-mediated activation of Ret prevents myogenic differentiation and could contribute to FSHD pathology by preventing satellite cell-mediated repair. Rescue of DUX4-induced pathology by Sunitinib highlights the therapeutic potential of tyrosine kinase inhibitors for treatment of FSHD

Active GSK3β and an intact β-catenin TCF complex are essential for the differentiation of human myogenic progenitor cells

CA was in receipt of a KCL studentship. The work was part funded by the BBSRC ref BB/L009943/1

Metabolomic and lipidomic plasma profile changes in human participants ascending to Everest Base Camp.

At high altitude oxygen delivery to the tissues is impaired leading to oxygen insufficiency (hypoxia). Acclimatisation requires adjustment to tissue metabolism, the details of which remain incompletely understood. Here, metabolic responses to progressive environmental hypoxia were assessed through metabolomic and lipidomic profiling of human plasma taken from 198 human participants before and during an ascent to Everest Base Camp (5,300 m). Aqueous and lipid fractions of plasma were separated and analysed using proton (1H)-nuclear magnetic resonance spectroscopy and direct infusion mass spectrometry, respectively. Bayesian robust hierarchical regression revealed decreasing isoleucine with ascent alongside increasing lactate and decreasing glucose, which may point towards increased glycolytic rate. Changes in the lipid profile with ascent included a decrease in triglycerides (48-50 carbons) associated with de novo lipogenesis, alongside increases in circulating levels of the most abundant free fatty acids (palmitic, linoleic and oleic acids). Together, this may be indicative of fat store mobilisation. This study provides the first broad metabolomic account of progressive exposure to environmental hypobaric hypoxia in healthy humans. Decreased isoleucine is of particular interest as a potential contributor to muscle catabolism observed with exposure to hypoxia at altitude. Substantial changes in lipid metabolism may represent important metabolic responses to sub-acute exposure to environmental hypoxia.King's College London, National Institute of Health Researc

The contributions of fibre atrophy, fibre loss, in situ specific force and voluntary activation to weakness in sarcopenia

The contributions of fibre atrophy, fibre loss, in situ specific force and voluntary activation to weakness in sarcopenia remain unclear. To investigate, forty older (20 women; age 72±4yrs) and 31 younger adults (15 women, age 22±3yrs) completed measurements. The knee extensor maximal voluntary torque (MVC) was measured as well as voluntary activation, patella tendon moment arm length, muscle volume and fascicle architecture to estimate in situ specific force. Fibre cross-sectional area (FCSA), fibre numbers and connective tissue contents were also estimated from vastus lateralis biopsies. The MVC, quadriceps volume and specific force were 39%, 28% and 17% lower, respectively, in old compared with young, but voluntary activation was not different. The difference in muscle size was due in almost equal proportions to lower type II FCSA and fewer fibres. Five years later (n=23) the MVC, muscle volume and voluntary activation in old decreased an additional 12%, 6% and 4%, respectively, but there was no further change in specific force. Conclusions: in situ specific force declines relatively early in older age and reduced voluntary activation occurs later, but the overall weakness in sarcopenia is mainly related to loss of both type I and II fibres and type II fibre atrophy

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent

Rapid Determination of Myosin Heavy Chain Expression in Rat, Mouse, and Human Skeletal Muscle Using Multicolor Immunofluorescence Analysis

Skeletal muscle is a heterogeneous tissue comprised of fibers with different morphological, functional, and metabolic properties. Different muscles contain varying proportions of fiber types; therefore, accurate identification is important. A number of histochemical methods are used to determine muscle fiber type; however, these techniques have several disadvantages. Immunofluorescence analysis is a sensitive method that allows for simultaneous evaluation of multiple MHC isoforms on a large number of fibers on a single cross-section, and offers a more precise means of identifying fiber types. In this investigation we characterized pure and hybrid fiber type distribution in 10 rat and 10 mouse skeletal muscles, as well as human vastus lateralis (VL) using multicolor immunofluorescence analysis. In addition, we determined fiber type-specific cross-sectional area (CSA), succinate dehydrogenase (SDH) activity, and α-glycerophosphate dehydrogenase (GPD) activity. Using this procedure we were able to easily identify pure and hybrid fiber populations in rat, mouse, and human muscle. Hybrid fibers were identified in all species and made up a significant portion of the total population in some rat and mouse muscles. For example, rat mixed gastrocnemius (MG) contained 12.2% hybrid fibers whereas mouse white tibialis anterior (WTA) contained 12.1% hybrid fibers. Collectively, we outline a simple and time-efficient method for determining MHC expression in skeletal muscle of multiple species. In addition, we provide a useful resource of the pure and hybrid fiber type distribution, fiber CSA, and relative fiber type-specific SDH and GPD activity in a number of rat and mouse muscles