L’œstradiol (E2) représente une cible thérapeutique potentielle contre le déclin de la mémoire associé au vieillissement. En effet, l’E2 favorise des mécanismes de plasticité synaptique, altérés par le vieillissement, censés sous-tendre la rétention mnésique. Cependant, la littérature révèle un tableau plus complexe, qui invite à reconsidérer les relations entre E2 et mémoire. Dans ce contexte, le but de cette thèse était d’améliorer notre compréhension des effets mnésiques d’une supplémentation chronique en E2 chez la souris mâle, jeune et âgée. Chez les animaux âgés, l’E2 réduit les déficits de la mémoire à long-terme dite « déclarative » en améliorant la capacité à relier des évènements séparés dans le temps en améliorant le fonctionnement du CA1 de l’hippocampe. En revanche, cette supplémentation reste sans effet sur le déficit observé dans une tâche de mémoire à court-terme sollicitant la gestion des interférences.Chez les animaux jeunes, l’E2 peut avoir des effets délétères sur la fonction mnésique normale. En effet, un prolongement de la rétention mnésique s’avère paradoxalement dommageable sur la mémoire à court-terme en aggravant les effets d’interférence. Cet effet s’accompagne d’une altération fonctionnelle centrée sur le gyrus denté hippocampique.Nos résultats comportementaux montrent que l’E2 prolonge la rétention mnésique mais que selon l’âge du sujet et la forme de mémoire mise en jeu par la tâche, cet effet « promnésiant » ne se traduit pas forcément par une amélioration de la performance.Ce travail invite aussi à considérer davantage les conséquences d’une exposition croissante aux composés œstrogénique de l’environnement sur la santé publique. / Estradiol (E2) is a potential therapeutic target against age-related memory decline. Indeed, E2 promotes synaptic plasticity processes impaired in aging and thought to underlie mnemonic retention. However, the literature reveals a much more complex picture, leading to reconsider the relationships between E2 and memory. The aim of my PhD work was to improve our understanding of the mnemonic effects of a chronic supplementation of E2 in young and aged male mice. In aged animals, E2 supplementation reduces hippocampal-dependent memory deficits called declarative memory, by improving the capacity to link temporally distant event which depends on CA1 functionality. However, the supplementation had no effect on the severe deficits of short-term/working memory which solicits not only retention but also the organization of learned information and forgetting to avoid interference. In young animals, E2 can induce deleterious effects on regular mnemonic function. Indeed, the prolongation of mnemonic retention can paradoxically imapir working memory by aggravating interference effects. This effect was associated with a functional alteration centered on dentate gyrus. Our behavioral results show that E2 prolongs mnemonic retention but, in accordance with our hypotheses, but depending on the age of the subject and the type of memory involved in the task, this promnesic effect does not necessarily induce an improved performance.Our work confirms the therapeutic interest of E2 in the context of mnemonic aging and allows pinpointing its limits. This work also invites to carefully consider the consequences of a growing exposition to environmental estrogenic compounds on public health.

Student Number : 9102778K - MSc(Eng) dissertation - School of Chemical and Metallurgical Engineering - Faculty of Engineering and the Built Environment / Strain ageing anisotropy, a surprising property of iron, implies that interstitials, which are non-lattice obstacles, can give non-symmetrical opposition to glide. Al- though this has been investigated by others, it is shown that it is di±cult to eliminate extraneous residual stresses during testing. An Avery torsion machine was adapted for the study of strain ageing anisotropy through the design of a torque and twist measurement system. This required the optimization of sensitivity, stiffness and me- chanical stability criteria, while ensuring practicality. When a ¯ne-grained sample with circumferential groove was tested a sharp yield point and lack of yield after ageing in the reverse direction was observed. Although more testing is required, it con¯rms the results of other researchers. In testing it was found that the quality of the sample machining was critical in achieving an accurate yield, and the groove design must be reviewed and improved. While the system measured to the required torque resolution, the strain measurement system could be improved by redesign and better calibration statistics.

Today in the United Kingdom (UK), ageing is considered to be an important aspect of social life in general and although overall South Asian Indians (SAIs) are relatively young compared to the indigenous white population, the number over the age of 60 is rapidly increasing. Over the last decade or so evidence-based practice within social work has been given a great deal of emphasis in public and professional life. This study is based in this spirit and emanates from personal and professional experience of working with an ageing population from a South Asian Indian background and focuses on the second and third generation of this settled minority. The aspect of co-residence within South Asian Indian cultures has been given little attention both within academic and professional studies. The key aims underpinning this work and of the research reported in this thesis were to illuminate and explicate the problematical and challenging expectations of ageing, co-residence and care within different generations of SAIs in Leicester. Thus this study investigates the expectations of co-residence and care amongst a cohort of second and third generation SAIs who have been settled in the UK for 30 or more years. Using interpretivist theoretical perspectives, 12 participants (8 from the second generation and 4 from the third generation of SAI ‘settlers’) were interviewed using in-depth semi-structured one-to-one interview techniques to collect data regarding their views and understandings of co-residence and care within the context of living in the UK. The data collected was thematically analysed and three themes, co-residence, expectations and acculturation/enculturation were identified for detailed exploration and analysis. Using interpretivist perspectives, these themes were used to identify meaningful patterns of behaviour and sentiment and to analyse the underlying symbolic sociocultural systems within the context of ageing within the SAI community in the United Kingdom. The research highlighted the onset of some enculturation processes and a rapid change in social attitudes, particularly in relation to altruism, concepts of family, a gap in understanding the expectations of co-residence between generations and the impact of these on second generation SAIs. The older participants yearned to be looked after by their adult children, feared being on their own and displayed anxiety at the prospect of not being looked after in their old age. They experienced and expressed concern at a loss of control in the decisions relating to co-residence for their current and future lives. The study points to the lack of wider scale academic and practice-based research studies focused on the impact of changes in culture and family expectations, particularly in relation to co-residence, and recommends that :(a) the academic and professional discourses and theories on ageing incorporate aspects and experiences of migration and diversity of cultures and (b) researchers, practitioners and policy makers examine the needs of the ageing SAI communities in the UK in order to explore policies, procedures and initiatives that could enhance various forms of family living and to develop relevant evidence - based practice. The outcomes of the research have implications for teaching and for practice. This is particularly so in cases where there has been a perceived failure to adopt understandings and practices in response to the identified changes. To this end a flow chart was developed that is recommended to be used as a guide and a tool for initial assessment for practitioners when working with this vulnerable group. It is hoped that this guide will have utility in terms of scope and reach when applied to the analysis and understanding of ageing in SAI communities in the UK.

The daily practice of bilingual language control has been argued to affect both lexical processing and non-verbal executive control in bilingual speakers. On the one hand, bilingualism may slow down lexical processing in both languages. On the other hand, bilinguals have been said to show cognitive advantages compared to monolinguals, for example on inhibition and switching tasks. However, this ‘bilingual advantage’ is hotly debated, can often not be replicated, and language groups have been poorly matched on background variables in previous studies. Furthermore, I examined the reliability of the literature and found evidence for the existence of a publication bias (Chapter 3). This over-representation of positive studies compared to studies with null or negative findings hinders a reliable interpretation of the actual effects of bilingualism. The current thesis therefore aimed to examine possible effects of bilingualism on both lexical processing and executive control. Specifically, I investigated the effects of an understudied, but important feature of bilingualism: language use. Effects of bilingualism have been argued to be largest in older adults. Chapter 4 presents a study discussing inhibition and possible effects of age across various tasks. I show that inhibitory control and age effects depend on task-specific features, including the type of interference, type of stimuli, and processing speed. Next, I present a study (Chapter 5 and 6) examining the relation between bilingualism and both lexical processing and executive control in older adults. Importantly, bilingual and monolingual groups were matched on background variables including immigrant status. I furthermore compared a group of active to inactive bilinguals to assess effects of language use. On a lexical processing task, bilinguals had a disadvantage compared to monolinguals. This effect was modulated by language use, implying that not only language proficiency but also actual language use are needed to explain lexical effects of bilingualism. However, the non-verbal executive control tasks showed no consistent effects of bilingualism or language use on inhibition or task switching. Thus, this study did not replicate positive effects on executive control in older adults. Between-subject comparisons remain problematic as groups can never be matched perfectly. Furthermore, these designs cannot assess a causal effect of bilingualism. Therefore, I conducted another study using behavioural and EEG measurements to test for causal effects of language switching on task switching (Chapter 7). When young bilinguals completed a language-switching task prior to a verbal task-switching paradigm, they showed larger switching costs than after a monolingual naming task. However, this effect of language switching was not found for non-verbal task switching. Language switching may thus have a negative impact on verbal switching, but these effects did not extend to non-verbal executive control. Together, these studies suggest that bilingualism and language use affect lexical processing, but there was no evidence for effects of bilingualism and language use on non-verbal executive control in younger or older adults. In combination with other failed replications and the biased literature, this questions the reliability of cognitive benefits associated with bilingualism. However, executive control is not a unity and its manifestation depends on task-specific features. This task impurity, together with the degree to which participant groups are matched, may explain the inconsistency with which effects of bilingualism on executive control have been observed.

Ageing and diabetes are two major healthcare concerns that used to be regarded as problems of the Western world but are now of increasing concern in developing nations. Treating elderly patients with diabetes poses issues for clinicians due to often complex, preexisting drug regimes. Research targeted at the development of novel drugs that have multiple effects on diabetes could go some way towards reducing polypharmacy in these patients. Here I present evidence that the oral Jak1/3 inhibitor, baricitinib, has effects on multiple aspects of diabetes. Baricitinib has been suggested to be a strong anti-inflammatory given the role Jak plays in transducing cytokine signals to elicit immune cell activation and maturation. Baricitinib was found to reduce urinary albumin to creatinine ratio and mesangial expansion in mice on an experimental high-fat diet with a diabetic metabolic profile when compared with naïve, non-diabetic mice. This reduction in renal impairment from diabetes was not found with a large reduction in proinflammatory cytokines and instead appears to be as a result of a direct effect on the cells of the mesangium. Baricitinib also reduced the circulating levels of cholesterol with a positive effect on the LDL: HDL ratio of diabetic mice. This reduction in cholesterol appears to be because of the abolition of GLP- 1 signalling, initiating an increase in blood insulin, preventing lipid flux and inhibiting LDL formation. Both of these changes in key diabetic complications were not accompanied by an increase in sensitivity to insulin compared with vehicle treated diabetic mice. These results show that baricitinib has a beneficial effect on two key aspects of the diabetic condition but that it does not modify insulin sensitivity itself. Baricitinib may represent a potential treatment for these diabetes-associated pathologies but only in combination with traditional anti-diabetic treatments.

O uso do cianeto em processos de eletrodeposição proporciona à prática industrial risco ambiental e ocupacional. Com isso, estudos têm buscado alternativas para a substituição desse agente nocivo. O Instituto de Pesquisas Tecnológicas (IPT) desenvolveu um banho de cobre alcalino sem cianeto, que utilizou como substituinte o HEDP (1-hidroxietano-1,1-difosfônico). Para a recuperação desse ácido a eletrodiálise foi avaliada, que consiste no uso de um sistema de membranas trocadoras de íons (MTI) e de corrente elétrica como força motriz. Meios oxidantes, corrosivos e com materiais orgânicos favorecem a degradação da membrana, inibindo sua capacidade em separação. Alternativas de manutenção têm sido estudadas para o aumento da vida útil das membranas, como o uso de agentes de limpeza. O estudo do envelhecimento proporciona a avaliação de um material em condições específicas, a fim de monitorar alterações em função do tempo de contato com o meio. O presente estudo propõe o envelhecimento de membranas aniônicas comerciais em soluções diluídas, provenientes do banho sintético de cobre à base de HEDP. Como objeto de estudo, foram selecionadas duas membranas, sendo uma heterogênea e uma membrana homogênea. Essas foram envelhecidas em três concentrações distintas (CuHEDP 1%, 5%, 10% v/v), por 400h de contato, sob agitação. As possíveis modificações estruturais foram avaliadas por meio de técnicas como a microscopia eletrônica de varredura acoplada à espectroscopia de energia dispersiva de raios-X (MEV-EDS), a análise termogravimétrica (TGA) e espectroscopia por infravermelho com transformada de Fourier (FTIR-ATR). As propriedades intrínsecas das membranas estão diretamente relacionadas ao seu caráter seletivo e morfológico. Para avaliar tais propriedades, foram utilizados ensaios cronopotenciométricos e a titulação potenciométrica. As propriedades investigadas foram o grau de inchamento, a capacidade de troca, a resistência elétrica, a densidade de corrente limite e a permeseletividade. Paralelamente, submeteu-se a membrana heterogênea ao envelhecimento em um sistema de eletrodiálise por 400h, monitorando-se as alterações em sua densidade de corrente e resistência elétrica a cada 100h de ensaio. Em adição, realizou-se a avaliação de agentes de limpeza de caráter ácido e básico, em concentrações distintas. O agente que atingiu melhor desempenho em remover a incorporação iônica foi aplicado às membranas envelhecidas em 100h de envelhecimento. Em seguida, essas foram reavaliadas a partir de ensaios eletroquímicos. Observou-se que houve interação entre os íons em solução e as membranas estudadas, que proporcionaram alterações em sua estrutura e propriedades, porém sem causar modificações que indicassem o descarte para ambas membranas. / The use of cyanide in electrodeposition processes provides industrial practice environmental and occupational risk. Thereby, studies have looked for alternatives for the substitution of this noxious agent. The Institute of Technological Research (ITR) developed an alkaline copper bath cyanide-free, which used HEDP (1-hydroxyethane- 1,1-diphosphonic) as a substitute. For the recovery of this acid the electrodialysis was evaluated, which consists of the use of an ion-exchange membrane (IEM) system and electric current as the driving force. Oxidizing, corrosive and organic materials favor membrane degradation, inhibiting their separation ability. Maintenance alternatives have been studied to increase the shelf life of membranes, such as the use of cleaning agents. The ageing study provides the evaluation of a material under specific conditions, in order to monitor changes as a function of the time of contact with the medium. The present study proposes the ageing of commercial anionic membranes in dilute solutions from the synthetic copper bath with HEDP. The purpose of the study was selected two membranes, being a heterogeneous and homogeneous membrane. These were aged in three distinct concentrations (CuHEDP 1%, 5%, 10% v/v) for 400 hours of contact, under stirring. The possible structural modifications were evaluated by techniques such as scanning electron microscopy coupled to X-ray dispersive energy spectroscopy (SEM-EDS), thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FTIR-ATR). The intrinsic properties of the membranes are directly related to their selective and morphological character. To evaluate such properties, chronopotentiometric assays and potentiometric titration were used. The investigated properties were swelling degree, ion-exchange capacity, electrical resistance, current density, and permselectivity. In parallel, the heterogeneous membrane was subjected to ageing in an electrodialysis system for 400h, monitoring the changes in its current density and electrical resistance every 100h of the test. In addition, acid and basic cleaning agents were evaluated in different concentrations. The agent that achieved the best performance in removing the ionic incorporation was applied to the membranes aged in 100h of ageing. These were then reevaluated from electrochemical tests. It was observed that there was interaction between the ions in solution and the membranes studied, which provided alterations in its structure and properties, but without provide modifications that indicated the need of disposal for both membranes.

It was 12:51pm on Tuesday the 22nd of February when a 6.2 magnitude earthquake struck the Canterbury region in New Zealand’s South Island. This earthquake devastatingly took the lives of 185 people and caused widespread damage across Christchurch and the Canterbury region. Since the February earthquake there has been 15,832 quakes in the Canterbury region. The impact of the earthquakes has resulted in ongoing social, material and political change which has shaped how everyday life is experienced. While the Christchurch earthquakes have been investigated in relation to a number of different angles and agendas, to date there has been a notable absence on how older people in Christchurch are experiencing post-disaster recovery. This PhD research attends to this omission and by drawing upon geographical scholarship on disasters and ageing to better understand the everyday experiences of post-disaster recovery for older people. This thesis identifies a lack of geographical attention to the emotional, affective and embodied experience of disaster. In response to this the thesis draws upon qualitative material collected from a six months fieldwork period to better understand the ways in which everyday life is lived out in an environment which has been social and materially altered. This thesis identifies three main interrelated themes which are productive for advancing understandings of how older people are situated in a post-disaster context. The first is that the concepts of emotion, affect and embodiment matter as they help inform how disasters are experienced and negotiated and the implication this has on various social and spatial relations. The second is that the disruption of the disaster to everyday places has implications on senses of belonging which is illustrated in highly temporal and affective dimensions. The third theme highlights the importance of recognising mundane and everyday practices as a means of coping and persisting with ongoing impacts of the disaster. This thesis argues that older people should not be seen as passive or homogenous agents in a disaster context but, in fact, are experiencing highly emotional impacts of disaster.

Visual function degrades with increasing age, in absence of frank disease, and affects both photopic and scotopic sensitivity. The mechanisms underlying these impairments may be related to biological (e.g., neural, optical) and environmental (e.g., smoking, dietary) factors. Recent evidence suggests that visual function may be improved following retinal carotenoid supplementation, both, in healthy and diseased eyes. Retinal carotenoids accumulate within the retina to form the macular pigment (MP) - a biomarker of antioxidant status of the eye and retinal disease risk. The objectives of this thesis were manyfold. First, the extent of vision loss (particularly scotopic sensitivity) in healthy ageing was examined. The results of this investigation showed that dark adaptation recovery slows with increasing age despite no significant change in visual acuity or fundus appearance. The technique described had excellent repeatability and correlated well with previous research. The potential link between MP and dark adaptation was also examined. The results showed that macular pigment optical density (MPOD) was correlated with a specific parameter of dark adaptation (S2) - a sensitive marker of functional degradation in normal ageing and retinal disease. The main part of this thesis sought to investigate the effect of MP augmentation on visual function in a large group of observers aged between 50 and 90 years old. The baseline data from this clinical trial revealed very interesting findings with regards to unhealthy lifestyle behaviours, health status and statin use. Subjects taking statins were identified (n = 25) and matched with 25 participants not using statins for age and body mass index. It was found that statin users had a higher proportion of males, higher prevalence of current smoking status and poorer general health (e.g. hypertension, high cholesterol and heart disease). Statin users also had significantly reduced MPOD, prolonged photostress recovery time, and deficits in a number of dark adaptation parameters. In a separate analysis of the whole group (n= 74, mean age 65.51), smokers were found to have reduced MPOD, slower S2, higher prevalence of high cholesterol and lower fruit and vegetable intake. MPOD was also reduced among obese subjects. The impact of MP augmentation on visual function in normal older subjects was assessed (n = 74, mean age 65.51) in a 12 month, randomized, double-blind, placebo-controlled study. Active formulation consisted of 20 mg lutein combined with vitamins and minerals. Data were collected at baseline, 6 months and 12 months. The results showed that, despite a 24% MPOD increase in the active group, there were no significant differences between the two groups over the three visits for any of the visual parameters. Given the increasing size of the older adult population in developed countries, research aimed at slowing or reversing age-related declines in vision is much needed both from an economical and psycho-social perspective. The results of the studies presented in this thesis show that lifestyle, health status and certain medications can adversely affect visual function in normal ageing. MP augmentation, however, had no effect on visual function. Further research is warranted, particularly paying close attention to subjects engaging in several unhealthy lifestyle/dietary behaviours, statin users and those with low MPOD and suboptimal visual function.

The research reported was inspired by the Perfect and Maylor (2000) chapter ‘Rejecting the Dull Hypothesis’. This suggested that cognitive ageing research should not focus purely on whether younger adults outperform older adults on a given task. Hartley, Speer, Jonides, Reuter-Lorez and Smith (2001) showed that older adults do not maintain the dissociability of naming identity, visual identity, and spatial location abilities that is seen in younger adults. Away from the ageing literature, Brown, Forbes and McConnell (2006) demonstrated improvement in visual task performance when the availability of verbal coding was increased. The hypothesis that older adults are less likely to use task specific cognitive mechanisms during short-term visual memory tasks was explored. This was carried out by means of a series of 8 experiments (outlined below), which broadly looked at differences in verbal interference effects on visual task performance, differences in Visual Patterns Task performance based on the availability of verbal encoding, and assessed for age-related differences in interference from an executive task in Visual Patterns Task performance. Data was interpreted through the prism of the Scaffolding Theory of Aging (Park & Reuter-Lorenz, 2009), which suggests that compensatory recruitment is employed both young and older adults in response to extrinsic challenges such as task difficulty, and intrinsic challenges, such as declining performance with age. Experiments 1-3 focused on differential effects of articulatory suppression on visual task performance between young (18-25) and older (60-75) adults. Older adults showed negative effects of suppression in short-term maintenance tasks that were not present in younger adults. Both age groups showed negative effects in a mental image rotation task. This suggested a level of verbal activation in visual tasks for both age groups, but that this activation was more common in older adults. Experiments 4-5 assessed differences in Visual Patterns Task performance between both age-groups depending on the availability of verbal encoding. Younger adults displayed the benefit of available verbal encoding with simultaneous but not sequential presentation of information. Older adults showed a benefit of verbal coding in the simultaneous task if the sequential task featured ordered, not randomised presentation pathways. This suggested that older adult task performance may be affected by all conditions within an experiment, not just the current manipulation condition. Experiments 6-7 demonstrated that older adults’ performance in the simultaneous presentation version of the Visual Patterns Task is affected by the availability of verbal encoding in the first task presented to them. Mean performance on subsequent conditions was higher when ‘high verbal coding’ patterns were seen in the first instance. This was not the case for younger adults. The demonstration of a benefit to performance from the ‘high-verbal coding’ pattern set compared to the ‘low-verbal coding’ set was a marker of higher overall performance across all task conditions for younger adults, but not for the older group. This suggested that even if verbal activation during visual task performance was an occurrence for older adults, it was not necessarily a marker for improved performance. Experiment 8 demonstrated that there were no age-related differences in the level of interference from an executive task (Random Month Generation) on Visual Patterns Task performance. This suggested that older adults do not try to actively recruit executive processes during Visual Patterns Task performance to any greater extent than younger adults do. It is suggested that older adults do use specialised task mechanisms to a lesser extent than younger adults in visual memory task performance. It is likely that this is a passive outcome of a decreased inhibition of verbal coding mechanisms, rather than an active attempt to maintain performance through the recruitment of executive cognitive resources. This is seen by the lack of age-group effects from executive interference tasks.

The aim of this research was to contribute to the growing body of academic literature regarding older women's stories of ageing. The initial impetus for the thesis came out of the disparity I observed between the way old women were often portrayed and the way older ageing was being lived by women I knew. Six women were recruited using an age range of 65 years and over and an association with a particular community organisation as recruitment guides. Two methods of data collection were used: diaries and semi-structured interviews. A qualitative narrative approach was taken to the data collection and analysis. The analysis revealed that the women viewed their ageing in a positive light. They constructed themselves as family orientated, as being and having friends and as active, independent participants within their own lives. Participants had clear ideas and expectations surrounding what they wanted from community participation and life in general. They spoke of the expectations of others and how these expectations sometimes lead to ageism and discrimination. Despite this it was apparent that being older had brought with it, for them, confidence, freedom, self-awareness and assertiveness. In short, these women required, actively sought, and usually accomplished, control of their own lives which involved places to go, people to see, things to do and most importantly the right to make their own choices.