Proceedings of the XIXth TELEMAC-MASCARET User Conference 2012, 18 to 19 October 2012, St Hugh's College, Oxford

Water Qualit

Vehicle and Traffic Safety

The book is devoted to contemporary issues regarding the safety of motor vehicles and road traffic. It presents the achievements of scientists, specialists, and industry representatives in the following selected areas of road transport safety and automotive engineering: active and passive vehicle safety, vehicle dynamics and stability, testing of vehicles (and their assemblies), including electric cars as well as autonomous vehicles. Selected issues from the area of accident analysis and reconstruction are discussed. The impact on road safety of aspects such as traffic control systems, road infrastructure, and human factors is also considered

The frail individual: uncovering the complexities in care and support across three common distinct settings.

Introduction By 2050, an estimated 2 billion people will be 65 years or older, bringing significant implications for health and social care. One implication – frailty – will affect patients, staff and healthcare settings. There is a need for improved recognition and care and support of frail individuals. Aims This thesis aims to uncover the complexities in the care and support of frail individuals across three distinct settings. A high-level study investigated the non-acute care setting, followed by investigating three distinct settings: community, acute hospital care and nursing homes. Methods A mixed-methods approach was used. Following a literature review, a survey (questionnaire) helped better understand ‘assessments for frailty’ used in the non-acute care setting. In the community setting, semi-structured interviews were undertaken with patients and healthcare professionals, using a participatory approach. In the acute care setting, a cross-sectional study of frail patients was conducted using patient data records. Regarding nursing homes, an online survey (questionnaire) helped investigate how frailty is assessed. Results Frailty is often understood and assessed as physical and mental health deficits. The perceptions of healthcare professionals and frail individuals regarding frail care and support networks overlap, but are distinct with different emphases. In acute care, variation in frail individuals’ living arrangement pre-admission and post-discharge was found, with a high proportion being discharged to a nursing home. Great variation in assessing for frailty was found in nursing homes. Conclusion Highlighted is the importance of family and friends in the care and support of frail individuals. Many hospital patients were discharged to settings with enhanced care and support availability, demonstrating the importance of care and support. ‘Assessing for frailty’ may require review to ensure holistic consideration of individuals and better frailty recognition. This may help improve the care and support of a frail individual and outcomes.Open Acces

Fuzzy Sets, Fuzzy Logic and Their Applications 2020

The present book contains the 24 total articles accepted and published in the Special Issue “Fuzzy Sets, Fuzzy Logic and Their Applications, 2020” of the MDPI Mathematics journal, which covers a wide range of topics connected to the theory and applications of fuzzy sets and systems of fuzzy logic and their extensions/generalizations. These topics include, among others, elements from fuzzy graphs; fuzzy numbers; fuzzy equations; fuzzy linear spaces; intuitionistic fuzzy sets; soft sets; type-2 fuzzy sets, bipolar fuzzy sets, plithogenic sets, fuzzy decision making, fuzzy governance, fuzzy models in mathematics of finance, a philosophical treatise on the connection of the scientific reasoning with fuzzy logic, etc. It is hoped that the book will be interesting and useful for those working in the area of fuzzy sets, fuzzy systems and fuzzy logic, as well as for those with the proper mathematical background and willing to become familiar with recent advances in fuzzy mathematics, which has become prevalent in almost all sectors of the human life and activity

An analysis of the immune and vascular systems in untreated hypertension

Background: Blood pressure regulation leads to hypertension through complex environmental and genetic interactions, mediated by cardiac, vascular, endocrine, and renal systems. The immune system interacts with all of these, and may have a role in hypertension and associated organ damage. Methods and Results: The Inflammatension study comprehensively assessed vascular function (endothelial function, arterial stiffness, intima-media thickness, and cardiovascular variability), the immune cell ‘signature’ (including B and T cell subsets, monocyte and dendritic cells, and intracellular stimulation studies), and circulating protein biomarkers, in an untreated hypertensive group compared to normotensive controls, and in consideration of phenotypic groups, as follows. Does cardiovascular function differ between incident hypertension versus healthy controls? Hypertensive disease progression involves early arterial stiffness. Carotid atherosclerosis and impairment in endothelial function were not detected. Measures of arterial stiffness strongly correlate with each other, with ambulatory and central BP, and with cardiovascular variability. Are phenotypic subgroups apparent in hypertension? White coat hypertension patients demonstrated arterial stiffening in excess of sustained hypertension; masked hypertension patients vascular characteristics were akin to normotension. Machine learning techniques generated three phenotypic groups of hypertension, ‘arterially stiffened’, ‘vaso-protected’, and ‘non-dipper’. Identifying immune cell ‘signature’ in patients: Flow cytometry demonstrated lower CD4+ naïve cells (CD45RA+CCR7+CD45RO+CD62L+) in hypertension. CD4+ T central memory cells were expanded in hypertension, along with CD62- T effector memory cells in an adjusted model. Hypertensive group had proportionally fewer CD28+ lymphocytes and CD8+ TEMRA cells, and T cells polarised towards Th1/Tc1 and Th17.1/Tc17.1. Intermediate monocytes demonstrated a differing pattern of CCR2 and CCR5 chemokine receptor expression, and alterations in STAT1 and STAT6 phosphorylation cascades. Increased NK cell CD56+Dim expression and reduced NKT and T lymphocytes CD122 expression was linked to hypertension. Nocturnal non-dipping was associated with similar immune cell signature changes as hypertension, and dendritic cell mannose receptor downregulation in addition. The circulating protein biomarker ‘signature’ of untreated hypertension and hypertensive phenotypes: Cytokines and chemokines dominated the 34 biomarkers differing between normotension and hypertension, though failed to meet Bonferroni-adjusted thresholds. Inflammatory biomarkers correlated with BP and arterial stiffness, but not endothelial function. Associations were concordant across systolic and diastolic BP; TPP1, CCL7, CCL11, and CCL21 positively correlating; IL18R1, and KYNU negatively. These relationships were more pronounced in the hypertensive subgroup, especially CD molecules and cytokines. HGF, AGE, and CCL21 showed greatest between-group differences and correlations across arterial parameters. Systolic nocturnal dipping demonstrated negative correlation with immune cell interaction and cellular adhesion biomarkers (CTRC, EPHA1, LGALS4, SIT1, SMOC, IL-18 and TNFSF11). Sixteen of the 85 correlating biomarkers also differed between the ‘arterially stiffened’, ‘vaso-protected’, and ‘non-dipper’ phenotypic groups. Conclusions: In untreated hypertension arterial stiffness is already detectable, and along with nocturnal dipping and estimates of central BP, categorise hypertensive phenotypes. The exploratory data support alterations of circulating immune biomarkers, and innate (monocytes) and adaptive (T cells) immune compartments. Nocturnal dipping and hypertension phenotypes especially demonstrate immune system variances

Imaging cerebrovascular alterations in experimental models of ageing and vascular cognitive impairment

Vascular cognitive impairment describes a heterogeneous condition in which cognitive decline is precipitated by underlying cerebrovascular dysfunction. Ageing, as well as vascular diseases such as hypertension, stroke, cerebral small vessel disease and cerebral amyloid angiopathy, are risk factors for vascular cognitive impairment. The precise mechanisms by which these conditions impact the cerebral vasculature to drive cognitive decline, however, are unknown. Previous research has indicated that vascular risk factors can lead to microvascular oxidative stress, inflammation and endothelial dysfunction that can lead to tissue hypoperfusion, the development of white and grey matter vascular lesions (microinfarcts and microbleeds) and cognitive impairment. It was hypothesised that ageing, a prominent risk factor for cognitive decline, would induce impairments on neurovascular coupling resulting from neurovascular unit disruption. It was further hypothesised that induction of chronic cerebral hypoperfusion would mediate neurovascular dysfunction and vascular lesion development through increased oxidative stress, resulting in cognitive decline. Finally, it was also hypothesised that neurovascular impairments resulting from ageing and chronic cerebral hypoperfusion would be exacerbated in the presence of amyloid deposition. Four studies were performed in order to test these hypotheses. Vascular risk factors can be reproduced using experimental mouse models and provide a valuable basis in which to test hypotheses and therapeutic interventions. As such, a primary aim of this thesis was to develop and validate sensitive MRI approaches that would allow the detection of vascular alterations in vivo. In the first series of studies, MRI techniques to assess resting cerebral blood flow, vessel number, vascular lesions and inflammation in experimental mice were validated using established in vivo and ex vivo techniques, so that these techniques could be used in subsequent studies for vascular assessments in vivo. Arterial spin labelling was developed to assess resting cerebral blood flow, and was able to detect reductions in blood flow following cerebral hypoperfusion that correlated well with those obtained from laser speckle imaging. Q-map imaging was able to detect reductions in vessel number in acute lesions, and in non-lesioned mice measures of vessel number correlated well with histopathological measures. Structural T2 imaging was performed in order to detect ischaemic and haemorrhagic lesions in chronically hypoperfused mice, and was validated using H&E and Perls’ staining. Finally, contrast-enhanced T2* imaging was used to detect iron oxide uptake by macrophages in the brains of hypoperfused mice, which was further validated by the identification of iron-containing macrophages in immunostained brain sections. The second study was conducted to test the hypothesis that ageing would impair neurovascular unit function and structure, and that these impairments would be exacerbated in the presence of amyloid pathology. The aim of the study was to incorporate previously developed in vivo imaging approaches in the assessment of vascular function and alterations in neurovascular unit structure in both wild type and TgSwDI mice. As predicted, ageing caused a pronounced deficit on measures of neurovascular coupling, however this was not exacerbated by accumulation of amyloid in TgSwDI mice and was not associated with alterations in baseline blood flow measured by arterial spin labelling. Structural assessment of the neurovascular unit revealed a loss of contact between astrocytic endfeet and vasculature, which was significantly associated with the impairment on neurovascular coupling, in addition to other markers of breakdown of the neurovascular unit such as loss of pericyte coverage and microglial activation. Age and thalamic vascular amyloid accumulation were also associated with an increase in the NADPH oxidase (NOX) subunit p47, indicative of increased oxidative stress. Data from this experiment indicate that ageing can profoundly impair neurovascular coupling, mediated by gliosis and loss of astrocytic contacts with vasculature. The third study aimed to test the hypothesis that chronic cerebral hypoperfusion (a prominent early feature of vascular cognitive impairment) would impair vascular function and induce the development of vascular lesions and cognitive decline. The impact of hypoperfusion on neurovascular coupling, ischaemic and haemorrhagic lesion burden and cognition was investigated in wild type and TgSwDI mice. Hypoperfusion induced deficits on neurovascular coupling, increased lesion burden and inflammation assessed with T2 and contrast-enhanced T2* imaging, and caused impairment on measures of learning and memory. Hypoperfusion was also associated with an increase in the levels of NOX2, NOX4 and 3-NT at 3 months following surgery, indicating persistent reactive oxygen species production and oxidative damage in hypoperfused mice. The findings from this study indicate that vascular dysfunction and cognitive impairment following hypoperfusion may be mediated by increased NADPH oxidase activity and resulting oxidative stress. The previous studies indicated that markers of oxidative stress were induced in response to ageing, vascular amyloid accumulation and cerebral hypoperfusion. The final study sought to determine whether increased NOX activity mediates downstream pathological effects on vascular function, vascular lesion development and cognitive decline following hypoperfusion. NOX activity was inhibited pharmacologically by administration of apocynin to hypoperfused TgSwDI mice for 3 months following surgery. Treatment with apocynin significantly restored neurovascular coupling to a level similar to sham-operated mice, and there was a trend toward reduction of ischaemic vascular lesions. However, it was unable to rescue the prominent inflammatory response or decline in cognitive ability, as apocynin-treated mice were no different on these measures to non-treated hypoperfused mice. The data indicate that whilst inhibiting NOX may have potential therapeutic value in improving vascular function, additional interventions, for example to reduce inflammation, may also be required in order to prevent cognitive decline. Overall, the work outlined within the thesis indicate that vascular risk factors of ageing, cerebral amyloid angiopathy and cerebral hypoperfusion may converge on common pathways involving oxidative stress and increased inflammation in order to drive vascular dysfunction and lead to cognitive decline. Inhibition of NOX activity was able to rescue vascular function, however the results indicate that this was not sufficient to protect against cognitive impairment, suggesting additional therapeutic targets may need to be sought in order to fully preserve vascular health and prevent cognitive decline