Modelling Apoptotic cell clearance within the atherosclerotic plaque

The aged population have an increased susceptibility to infection, therefore function of the innate immune system may be impaired as we age. Macrophages, and their precursors monocytes, play an important role in host defence in the form of phagocytosis, and also link the innate and adaptive immune system via antigen presentation. Classically-activated 'M1' macrophages are pro-inflammatory, which can be induced by encountering pathogenic material or pro-inflammatory mediators. Alternatively activated 'M2' macrophages have a largely reparative role, including clearance of apoptotic bodies and debris from tissues. Despite some innate immune receptors being implicated in the clearance of apoptotic cells, the process has been observed to have a dominant anti-inflammatory phenotype with cytokines such as IL-10 and TGF-ß being implicated. The atherosclerotic plaque contains recruited monocytes and macrophages, and is a highly inflammatory environment despite high levels of apoptosis. At these sites, monocytes differentiate into macrophages and gorge on lipoproteins, resulting in formation of 'foam cells' which then undergo apoptosis, recruiting further monocytes. This project seeks to understand why, given high levels of apoptosis, the plaque is a pro-inflammatory environment. This phenomenon may be the result of the aged environment or an inability of foam cells to elicit an anti-inflammatory effect in response to dying cells. Here we demonstrate that lipoprotein treatment of macrophages in culture results in reduced capacity to clear apoptotic cells. The effect of lipoprotein treatment on apoptotic cell-mediated immune modulation of macrophage function is currently under study.

Reduced transferrin binding in Down syndrome:a route to senile plaque formation and dementia

Plasma transferrin binding in Down syndrome and Alzheimer's disease is significantly reduced compared with age matched controls and it was thought this may help elucidate a pathological time sequence for the onset of dementia in Down syndrome. In Down syndrome, there was a reduction in gallium and aluminium transferrin binding both with age and the onset of dementia. Non-transferrin bound gallium species were identified as non-transportable phosphate or silicate. Thus, the route of entry of metals into the brain must be via a transferrin mediated complex only. A clear sequence of pathological events has been demonstrated in Down syndrome which shows the pathway to development of plaques and dementia and this is believed to have an immunological origin.

Between safety and vulnerability:the exiled other of international relations

Inspired by the idea of safe citizenship this article queries the possibilities of safety in an age of securitization. It challenges the cosmopolitan worldview and its iteration of a global cosmopolitan citizen. It champions an account of affective citizenship, narration and attends to the trauma of exile. It offers an account of exile before suggesting an institutional design premised on politicization. This design, it is argued, facilitates moments of storytelling fostering individual empowerment. This unorthodox rendering of agency allows the traumatized exile to negotiate the world as it is, not as it could be, as a potential ‘safe’ citizen.

Relationships between morphological types of plaque in Alzheimer’s disease as revealed in silver and immunostained preparations

The objective of this study was to determine the possible relationships between the morphological types of plaque revealed in silver and immunostained sections of Alzheimer’s disease (AD) tissue. The density of cored and uncored senile plaques in Glees and Marsland preparations, and of diffuse, primitive, classic and compact beta/A4 deposits in immunostained preparations were estimated. A principal components analysis (PCA) of the data suggested that three uncorrelated principal components accounted for 80% of the variation in lesion density in the tissues. This suggested that thee processes lead independently to the formation of: (1) the uncored Glees plaques; (2) the primitive beta/A4 deposits and most of the classic beta/A4 deposits and (3) the compact beta/A4 deposits and the remaining classic deposits. Hence, the uncored plaques revealed by the Glees stain and the primitive beta/A4 deposits represented distinct plaque populations. In addition, the classic beta/A4 deposits did not appear to represent a uniform plaque population but to originate from at least two pathological processes. The uncored Glees plaques appeared to the only plaque population closely related to the diffuse beta/A4 deposits.

The usefulness of spatial pattern analysis in understanding the pathogenesis of neurodegenerative disorders, with particular reference to plaque formation in Alzheimer's disease

Discrete, microscopic lesions are developed in the brain in a number of neurodegenerative diseases. These lesions may not be randomly distributed in the tissue but exhibit a spatial pattern, i.e., a departure from randomness towards regularlity or clustering. The spatial pattern of a lesion may reflect its development in relation to other brain lesions or to neuroanatomical structures. Hence, a study of spatial pattern may help to elucidate the pathogenesis of a lesion. A number of statistical methods can be used to study the spatial patterns of brain lesions. They range from simple tests of whether the distribution of a lesion departs from random to more complex methods which can detect clustering and the size, distribution and spacing of clusters. This paper reviews the uses and limitations of these methods as applied to neurodegenerative disorders, and in particular to senile plaque formation in Alzheimer's disease.

Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces:state versus trait vulnerability markers of depression in bipolar disorder

Background - Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD). Methods - Thirty-one BD (type I; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined. Results - The BD versus HC showed significantly greater right amygdala-OFC FC (p = .001) in the sad experiment and significantly reduced bilateral amygdala-OFC FC (p = .007) in the happy experiment. Depressed but not remitted female BD versus female HC showed significantly greater left amygdala-OFC FC (p = .001) to all faces in the sad experiment and reduced bilateral amygdala-OFC FC to intense happy faces (p = .01). There was a significant nonlinear relationship (p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001). Conclusions - In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC–FA relationships in BD and HC require further study.

Perception of risk, feelings of vulnerability and effects on driving behaviour in women drivers across the lifespan.

Sustained driving in older age has implications for quality of life and mental health. Studies have shown that despite the recognised importance of driving in maintaining health and social engagement, many women give up driving prematurely or adopt self-imposed restrictive driving practices. Emotional responses to driving have been implicated in these decisions. This research examined the effect of risk perception and feelings of vulnerability on women’s driving behaviour across the lifespan. It also developed and tested a modified theory of planned behaviour intervention to positively affect driving habits. The first two studies (N=395) used quantitative analysis to model driving behaviours affected by risk perception and feelings of vulnerability, and established that feelings of vulnerability do indeed affect women’s driving behaviour, specifically resulting in increases in driving avoidance and the adoption of maladaptive driving styles. Further, that self-regulation, conceptualised as avoidance, is used by drivers across the lifespan. Qualitative analysis of focus group data (N=48) in the third study provided a deeper understanding of the variations in coping behaviours adopted by sub-groups of drivers and extended the definition of self-regulation to incorporate adaptive coping strategies. The next study (N=64) reported the construction and preliminary validation of the novel self-regulation index (SRI) to measure wider self-regulation behaviours using an objective measure of driving behaviour, a simulated driving task. The understanding gained from the formative research was used in the final study, an extended theory of planned behaviour intervention to promote wider self-regulation behaviour, measured using the previously validated self-regulation index. The intervention achieved moderate success with changes in affective attitude and normative beliefs as well as self-reported behaviour. The results offer promise for self-regulation, incorporating a spectrum of planning and coping behaviours, to be used as a mechanism to assist drivers in achieving their personal mobility goals whilst promoting safe driving.

Watermark-only security attack on DM-QIM watermarking:vulnerability to guided key guessing

This paper addresses the security of a specific class of common watermarking methods based on Dither modulation-quantisation index modulation (DM-QIM) and focusing on watermark-only attacks (WOA). The vulnerabilities of and probable attacks on lattice structure based watermark embedding methods have been presented in the literature. DM-QIM is one of the best known lattice structure based watermarking techniques. In this paper, the authors discuss a watermark-only attack scenario (the attacker has access to a single watermarked content only). In the literature it is an assumption that DM-QIM methods are secure to WOA. However, the authors show that the DM-QIM based embedding method is vulnerable against a guided key guessing attack by exploiting subtle statistical regularities in the feature space embeddings for time series and images. Using a distribution-free algorithm, this paper presents an analysis of the attack and numerical results for multiple examples of image and time series data.

Watermark-only security attack on DM-QIM watermarking:vulnerability to guided key guessing

This paper addresses the security of a specific class of common watermarking methods based on Dither modulation-quantisation index modulation (DM-QIM) and focusing on watermark-only attacks (WOA). The vulnerabilities of and probable attacks on lattice structure based watermark embedding methods have been presented in the literature. DM-QIM is one of the best known lattice structure based watermarking techniques. In this paper, the authors discuss a watermark-only attack scenario (the attacker has access to a single watermarked content only). In the literature it is an assumption that DM-QIM methods are secure to WOA. However, the authors show that the DM-QIM based embedding method is vulnerable against a guided key guessing attack by exploiting subtle statistical regularities in the feature space embeddings for time series and images. Using a distribution-free algorithm, this paper presents an analysis of the attack and numerical results for multiple examples of image and time series data.

Agency as vulnerability:accounting for children's movement to the streets of Accra

This paper considers the agency of children moving to the streets of Accra, Ghana's capital city. A much used but largely unexamined concept, agency is nevertheless commonly deployed in childhood studies as a means to stress the capacity of children to choose to do things. In the literature on street and working children, and a cognate area of study concerned with children's independent migration, this has involved accounts of children's agency made meaningful by reference to theories of rational choice or to the normative force of childhood. It is our argument that both approaches leave unanswered important questions and to counter these omissions we draw upon the arguments of social realists and, in particular, the stress they place on vulnerability as the basis for human agency. We develop this argument further by reference to our research with street children. By drawing upon the children's accounts of leaving their households and heading for Accra's streets, it is our contention that these children do frame their departures as matters of individual choice and self-determination, and that in doing so they speak of a considerable capacity for action. Nevertheless, a deeper reading of their testimonies also points to the children's understandings of their own vulnerability. By examining what we see as their inability to be dependent upon family and kin, we stress the importance of the children's perceptions of their vulnerability, frailty and need as the basis for a fuller understanding of their agency in leaving their households. © 2013 The Author. The Sociological Review © 2013 The Editorial Board of The Sociological Review.

Characterisation of staphylococci associated with atopic eczema and chronic plaque psoriasis

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Feelings of vulnerability and effects on driving behaviour:a qualitative study

Feelings of vulnerability in driving can be considered an emotional response to risk perception and the coping strategies adopted could have implications for continued mobility. In a series of focus groups with 48 licensed drivers aged 18-75 years, expressions of vulnerability in driver coping behaviours were examined. Despite feelings of vulnerability appearing low, qualitative thematic analysis revealed a complex array of coping strategies in everyday driving including planning, use of 'co-pilots', self-regulation, avoidance and confrontive coping, i.e. intentional aggression toward other road users. The findings inform future intervention studies to enable appropriate coping strategy selection and prolong independent mobility in older adults. © 2014 Elsevier Ltd. All rights reserved.

Evaluation of vulnerability factors for cyclones : the case of Patuakhali, Bangladesh

Tropical cyclones are considered as the most severe natural disasters in Bangladesh; they cause extensive damage, create losses in the country׳s economy, and affect social settings. The impact of natural disasters has been further intensified due to various vulnerability factors within the Bangladeshi community such as low income; shortages of food; lack of assets such as land and permanent housing; dense population, illiteracy. This study evaluates the vulnerability factors for cyclones in the community based in the Patuakhali region of south western Bangladesh. The bottom-up research approach was adopted for the study, whereby the local community was consulted for their viewpoints by using focus group interviews and semi-structured interviews. Different community groups and social categories including both men and women, from different age groups and livelihoods, participated in the study. The study revealed how the community׳s vulnerability to cyclones has been further aggravated by socio-economic factors such as social status, political influences and economic conditions. The majority of the community in Patuakhali has been “knowingly” vulnerable to cyclone disaster as a result of the lack of alternatives especially in terms of their livelihood patterns. The vulnerability of women, due to their lack of authority, domestic work, and fear of exposure within the society was also highlighted. The study revealed how vulnerability factors are interlinked with each other making them further difficult to manage. This calls for multi-faceted disaster risk reduction strategies that targets vulnerability factors deriving from different origins and root causes.