Browsing by Author "Aspinall, Richard"

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    The design and evaluation of discrete wearable medical devices for vital signs monitoring
    (Cranfield University, 2015) Pitts, David Geoffrey; Cellek, Selim; Aspinall, Richard; Sinclair, Alan
    The observation, recording and appraisal of an individual’s vital signs, namely temperature, heart rate, blood pressure, respiratory rate and blood oxygen saturation (SpO2), are key components in the assessment of their health and wellbeing. Measurements provide valuable diagnostic data, facilitating clinical diagnosis, management and monitoring. Respiratory rate sensing is perhaps the most under-utilised of all the vital signs, being routinely assessed by observation or estimated algorithmically from respiratory-induced beat-to-beat variation in heart rate. Moreover there is an unmet need for wearable devices that can measure all or most of the vital signs. This project therefore aims to a) develop a device that can measure respiratory rate and b) develop a wearable device that can measure all or most of the vital signs. An accelerometer-based clavicular respiratory motion sensor was developed and compared with a similar thoracic motion sensor and reference using exhalatory flow. Pilot study results established that the clavicle sensor accurately tracked the reference in monitoring respiratory rate and outperformed the thoracic device. An Ear-worn Patient Monitoring System (EPMS) was also developed, providing a discrete telemonitoring device capable of rapidly measuring tympanic temperature, heart rate, SpO2 and activity level. The results of a comparative pilot study against reference instruments revealed that heart rate matched the reference for accuracy, while temperature under read (< 1°C) and SpO2 was inconsistent with poor correlation. In conclusion, both of the prototype devices require further development. The respiratory sensor would benefit from product engineering and larger scale testing to fully exploit the technology, but could find use in both hospital and community-based The design and evaluation of discrete wearable medical devices for vital signs monitoring DG Pitts ii Cranfield University monitoring. The EPMS has potential for clinical and community use, having demonstrated its capability of rapidly capturing and wirelessly transmitting vital signs readings. Further development is nevertheless required to improve the thermometer probe and resolve outstanding issues with SpO2 readings.
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    Effectiveness of influenza vaccine in aging and older adults: comprehensive analysis of the evidence
    (Dove Medical Press, 2012-02-23T00:00:00Z) Lang, Pierre-Olivier; Mendes, Aline; Socquet, Jennifer; Assir, Noémie; Govind, Sheila; Aspinall, Richard
    Foremost amongst the diseases preventable by vaccination is influenza. Worldwide, influenza virus infection is associated with serious adverse events leading to hospitalization, debilitating complications, and death in elderly individuals. Immunization is considered to be the cornerstone for preventing these adverse health outcomes, and vaccination programs are timed to optimize protection during the annual influenza season. Trivalent inactivated influenza virus vaccines are believed to be both effective and cost-saving; however, in spite of widespread influenza vaccination programs, rates of hospitalization for acute respiratory illness and cardiovascular diseases have been increasing in this population during recent annual influenza seasons. From meta-analyses summarizing estimates of influenza vaccine effectiveness from available observational clinical studies, this review aims to examine how effective current influenza vaccine strategies are in the aging and older adult population and to analyze which are the most important biases that interfere with measurements of influenza vaccine effectiveness. Furthermore, consideration is given to strategies that should be adopted in order to optimize influenza vaccine effectiveness in the face of immune exhaustion.
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    Immunotherapy of immunosenesence; who, how and when?
    (Bentham open, 2012-12-31T00:00:00Z) Govind, Sheila; Lapenna, Antonio; Lang, Pierre-Olivier; Aspinall, Richard
    Major changes in social welfare, economic conditions and medical knowledge over the last 60 years have pro-duced a demographic shift in the population. More individuals are living longer, and in a decade there will be more people over 65 than infants under 5 for the first time in history. Taking the analysis beyond mere numbers reveals that older indi-viduals are now physically more active than their forebears and travel more widely. This provides a greater opportunity for encountering infectious agents which could present a considerable problem. Older individuals are more susceptible to infection and do not respond as well as younger people to vaccination because of an age related decline in immunity, a state which has been termed immunosenesence. This decline is not uniform and some older individuals show a greater de-cline in their immune response than others. In this review we have sought to consider who are the ‘at risk' individuals, how they might best be treated and when.
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    Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring
    (Public Library of Science (PLoS), 2011-06-30T00:00:00Z) Aspinall, Richard; Prentice, A. M.; Ngom, P. T.
    Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue.
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    Protection versus pathology in aviremic and high viral load HIV-2 infection—The pivotal role of immune activation and T-cell kinetics
    (University of Chicago Press / Oxford University Press, 2014-05-05) Hegedus, Andrea; Nyamweya, Samuel; Zhang, Yan; Govind, Sheila; Aspinall, Richard; Mashanova, Alla; Jansen, Vincent A. A.; Whittle, Hilton; Jaye, Assan; Flanagan, Katie L.; Macallan, Derek C.
    Background. Many human immunodeficiency virus (HIV)–2-infected individuals remain aviremic and behave as long-term non-progressors but some progress to AIDS. We hypothesized that immune activation and T-cell turnover would be critical determinants of non-progressor/progressor status. Methods. We studied 37 subjects in The Gambia, West Africa: 10 HIV-negative controls, 10 HIV-2-infected subjects with low viral loads (HIV-2-LV), 7 HIV-2-infected subjects with high viral loads (HIV-2-HV), and 10 with HIV-1 infection. We measured in vivo T-cell turnover using deuterium-glucose labeling, and correlated results with T-cell phenotype (by flow cytometry) and T-cell receptor excision circle (TREC) abundance. Results. Immune activation (HLA-DR/CD38 coexpression) differed between groups with a significant trend: controls
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    A Simple Model System Enabling Human CD34+ Cells to Undertake Differentiation Towards T Cells
    (Public Library of Science (PLoS), 2013-07-23T00:00:00Z) Lapenna, Antonio; B-Lynch, C.; Kapeni, C.; Aspinall, Richard
    Channelling the development of haematopoietic progenitor cells into T lymphocytes is dependent upon a series of extrinsic prompts whose temporal and spatial sequence is critical for a productive outcome. Simple models of human progenitor cells development depend in the main on the use of xenogeneic systems which may provide some limitations to development. Here we provide evidence that a simple model system which utilises both human keratinocyte and fibroblast cell lines arrayed on a synthetic tantalum coated matrix provides a permissive environment for the development of human CD34⁺ haematopoietic cells into mature CD4⁺ or CD8⁺ T lymphocytes in the presence of Interleukin 7 (IL-7), Interleukin 15 (IL-15) and the Fms-like tyrosine kinase 3 ligand (Flt-3L). This system was used to compare the ability of CD34(+) cells to produce mature thymocytes and showed that whilst these cells derived from cord blood were able to productively differentiate into thymocytes the system was not permissive for the development of CD34(+) cells from adult peripheral blood. Our study provides direct evidence for the capacity of human cord blood CD34(+) cells to differentiate along the T lineage in a simple human model system. Productive commitment of the CD34⁺ cells to generate T cells was found to be dependent on a three-dimensional matrix which induced the up-regulation of the Notch delta-like ligand 4 (Dll-4) by epithelial cells.
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    T cells development in vitro : a minimalist approach
    (Cranfield University, 2012-04) Lapenna, Antonio; Aspinall, Richard
    T lymphocytes are considered an essential and advanced component of the immune system, since these cells are able to discriminate self from non-self, start up an immune reaction and further develop into memory cells. However, therapies based on the use of patient derived newly generated T cells reinoculated into humans do not exist. This is due to difficulties in replicating the peculiar conditions required for T cell development in vitro. The systems developed so far are based on the use of animal or unrelated human thymic tissue and therefore they would not be adequate to be used in any clinical application. Having conjectured that human skin cells, rearranged in a threedimensional fashion, would be able to support the development of human T lymphocytes from hematopoietic stem cells, we developed a model consisting of human skin keratinocytes and fibroblasts arrayed on a synthetic matrix so to create a prototype suitable to be translated into the clinic. In this way we were able to induce few hundred cord blood CD34⁺ haematopoietic stem cells to entirely develop into mature CD4⁺ or CD8⁺ T lymphocytes in vitro. However, circulating adult peripheral CD34⁺ precursors failed to survive in the same conditions. Finally we were able to explain our success as consequence of strong induction of the Notch delta ligand Dll-4 by the keratinocytes cultured in the construct. In synthesis, we report here for the first time that skin keratinocytes, in the presence of fibroblasts and reconfigured in a three-dimensional arrangement, are able to induce the differentiation of a minimal amount of cord but not adult blood stem cells into fully differentiated T cells by acting through the Dll-4 Notch signaling pathway in vitro.
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    Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden
    (S. Karger AG / BioMed Central, 2011-06-15T00:00:00Z) Ngom, P. T.; Solon, J.; Moore, S. E.; Morgan, G.; Prentice, A. M.; Aspinall, Richard
    BACKGROUND:The study exploits a natural human experimental model of subsistence farmers experiencing chronic and seasonally modified food shortages and infectious burden. Two seasons existed, one of increased deprivation and infections (Jul-Dec), another of abundance and low infections (Jan-Jun); referred to as the hungry/high infection and harvest/low infection seasons respectively. Prior analysis showed a 10-fold excess in infectious disease associated mortality in young adults born in the hungry/high infection versus harvest/low infection season, and reduced thymic output and T cell counts in infancy. Here we report findings on the role of early life stressors as contributors to the onset of T cell immunological defects in later life. METHODS:We hypothesised that season of birth effects on thymic function and T cell immunity would be detectable in young adults since Kaplan-Meier survival curves indicated this to be the time of greatest mortality divergence. T cell subset analyses by flow-cytometry, sjTRECs, TCRVβ repertoire and telomere length by PCR, were performed on samples from 60 males (18-23 y) selected to represent births in the hungry/high infection and harvest/low infection RESULTS:Total lymphocyte counts were normal and did not differ by birth season. CD3+ and CD4+ but not CD8+ counts were lower for those born during the hungry/high infection season. CD8+ telomere length also tended to be shorter. Overall, CD8+ TCRVβ repertoire skewing was observed with 'public' expressions and deletions seen in TCRVβ12/22 and TCRVβ24, respectively but no apparent effect of birth season. CONCLUSIONS:We conclude that, although thymic function was unchanged, the CD4+ and CD3+ counts, and CD8+ telomere length results suggested that aspects of adult T cell immunity were under the influence of early life stressors. The endemicity of CMV and HBV suggested that chronic infections may modulate immunity through T cell repertoire development. The overall implications being that, this population is at an elevated risk of premature immunosenescence possibly driven by a combination of nutritional and infectious bur