This thesis derives and validates Performance Indicators for Safe Mobility for Older Road Users in Urban Areas. Performance Indicators are objective, auditable parameters, which when used as a set can provide additional information to decision-makers about the operation of the transport system. Great Britain, in common with many countries across Europe has an ageing population. The proportion of older people who hold a driving licence and have the use of a car is also expected to rise, with future generations of older people travelling further and more frequently than previous generations. Older road users are already over-represented in traffic fatalities, particularly in urban areas. Measures to protect older road users from risk in traffic will be of crucial importance as the population ages. However, against this background the need remains for them to access key facilities such as shops, leisure activities and health care. Maintaining independent mobility is essential in maintaining mental and physical health. Traditionally, outcomes-based measures such as accident or casualty figures have been used to monitor road safety. Techniques such as hotspot analysis have identified locations on the road network where accident numbers are high, allowing modifications to road infrastructure to be designed and implemented. Using outcomes measures alone however, it is difficult to ascribe improvements in accident or casualty figures to particular policy interventions. Moreover, the effect of road safety interventions on other related policy areas mobility being one is impossible to assess without access to detailed, disaggregated exposure data. To make fully informed policy decisions about infrastructure design and how it affects older users, a better understanding of the linkages between safety and mobility is required. Performance Indicators offer the possibility to look at these linked policy objectives within a single framework. Focus group data was used in conjunction with the results of previous studies to identify the infrastructure features which present a barrier to older users safe mobility in urban areas. These included factors which increased risk, such as wide carriageways, complex junctions and fast-moving traffic, and factors which hindered mobility, such as uneven or poorly maintained pavements, poor lighting and traffic intrusion. A thematic audit of infrastructure in a case study city (Coventry) was undertaken, in order that the incidence of such infrastructure could be recorded. It was found that in many areas of the city, safe mobility for older road users was not well provided for, with the majority of locations having barriers to safety and/or mobility for both drivers and pedestrians. The audit data was then used to calculate a set of Performance Indicators, presented via spider graphs, which describe the degree to which the infrastructure caters for the safety and mobility of older drivers and pedestrians. The spider graphs allow for easy comparisons between the different geographical areas, and also between the different policy areas, allowing policy priorities to be identified. The calculated Performance Indicators were validated using case studies collected from the focus group participants. The case studies identified features that affected travel habits by causing a change of route or change of mode, providing evidence of the link between infrastructure design and safe mobility for older users. The results of the Performance Indicator analysis were then compared to accident figures, in order to identify differences between the two approaches, and to understand what policy implications would result from a monitoring framework that used Performance Indicators for safe mobility, rather than outcomes-based measures alone. One implication of the Performance Indicator approach is that it may identify different areas for priority action from those identified by accident or casualty figures. A location which does not have high accident numbers may nevertheless perform poorly on a Safety Performance Indicator measure. This is because older users who feel at risk make different route or mode choices to avoid the infrastructure, the lower accident rate being explained by lower exposure to risk. Conversely, measures to promote independent mobility for older users may increase their accident involvement, not because the environment becomes more risky, but because the exposure of older users to risk increases, because they are willing and able to walk or drive in an area they previously avoided. The thesis concludes that infrastructure design does not currently cater well for the needs of older pedestrians and drivers, and that a framework which incorporated Performance Indicators could make more explicit the trade-offs between safety and mobility, and between different categories of user. This additional information would enable policy makers and practitioners to make more informed decisions about how to prioritise competing objectives in complex urban areas.

It is important to establish the role of age in face-processing since perceived-age is a dimension that may be used to encode faces within memory. While previous research has demonstrated faces can be categorised by age, a question that has not been addressed is how well people are able to do so. This study identifies the extent to which people can categorise faces on the basis of age and also explores the nature of the visual information used for this. The evidence suggests that age-perception is much more complex than has been previously suggested. Using realistic faces as stimuli, it becomes apparent that people are adept at using a wide variety of cues to age. Overall, this demonstrates that we have a sophisticated understanding of the changes that occur through ageing, that we can use with a high degree of subtlety and accuracy. Given the robust nature of information about age and the ability to which it can be used to differentiate faces, age must be influential at encoding. However, the ability to determine and encode a face's physical properties at one point in time can not be a full explanation for the way faces are represented simply because those physical properties do not stay the same over time. The ageing face can therefore be used as a tool to gain greater insight into what facial information is utilised for individual recognition. This was investigated using a recognition paradigm where the individual faces were of different ages to those initially presented and hence displayed different physical properties. The evidence shows that recognition despite age-induced changes is possible; this implies that there is not a one to one mapping between the physical properties at encoding and those that the memory system operates on to accomplish recognition.

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No description available.

Safe and efficient swallowing requires integrity of both motor and sensory systems. Prior studies have established that motor impairment in individuals with PD frequently manifests as abnormalities in swallowing biomechanics. In contrast, very few studies have investigated the contribution of sensory impairment towards pharyngeal biomechanics and airway protection in this patient cohort. This area should be addressed in light of evidence that the severity of limb motor dysfunction in PD does not reliably predict severity of dysphagia. Emerging data suggests that dysphagia in PD cannot be solely attributed to motor impairment, but may also be influenced by deficits in sensory aspects of airway protection. As an example, silent aspiration in up to 100% has been reported in individuals with PD due to laryngopharyngeal sensory deficits have. Even so, current research lacks information on the integration of both motor and sensory components that make up the swallowing process. The aim of this study was to document changes in airway protection with age, in PD and across severity levels of PD. The project was comprised of two parts. In part one, three parallel studies were conducted to assess a series of both motor and sensory airway mechanism (Chapters 4 to 9). In the first study, 16 young (8 males, age range 21.3 - 32.4) and 16 elder adults (8 males, age range 61.5 - 84.7), were assessed to investigate changes in airway protection that accompany ageing. In the second study, data from individuals diagnosed with PD across severity levels (Hoehn-Yahr 1 - 4, age range 64.2 - 84.5) were age and gender-matched to 16 healthy elders in order to examine the effects of PD on airway protection. In the third, the impact of disease severity was studied with data from 16 individuals in the earlier stages (Hoehn-Yahr ≤ 2, 13 males, age range 51.3 - 82.5, ) compared to 16 individuals in the later stages (Hoehn-Yahr ≥ 2.5, 10 males, age range 61.5 - 78.9). In part two of this project, two smaller, pilot studies were completed to probe the influence of pharmacologic and behavioural treatments on airway protection mechanisms. In the first pilot study, the effect of pharmacotherapy on airway protection was investigated in 10 patients 'on' and 'off' levodopa (Chapter 10). In the second study, 5 patients were assessed before and after completing the Lee Silverman Voice Treatment (LSVT) to document effects of speech rehabilitation on airway protection (Chapter 11). Multimodality assessment elicited data from all participants on both motor and sensory components of airway protection (Chapter 3). Specifically, breathing-swallowing coordination (BSC) and swallowing apnoea (SA) were captured using simultaneous directional nasal airflow and surface electromyography (sEMG). Standard, closed-loop spirometry was used to assess pulmonary function. Swallowing biomechanics were screened using a validated timed test of swallowing efficiency and further evaluated using fibreoptic endoscopic evaluation of swallowing (FEES). Finally, chemo-sensation of the laryngopharynx was determined with the administration of the inhalation cough challenge while mechanosensation was examined using FEES. Results suggest that motor control for airway protection is reasonably robust in PD, although sensory response is impaired. The predominant pattern for swallowing respiratory coordination was mid-expiration for all participants regardless of age and disease severity (Chapter 4). Individuals with PD demonstrated a reduction in average time and volume per swallow, leading to an overall decrease in swallowing capacity (Chapter 5). No difference was found for swallowing efficiency between those in early and later stages of PD. Pulmonary function measures were not significantly different as a function of age, PD or PD severity (Chapter 6). In summary, results from motor assessments contributing to airway protection support the robustness of breathing-swallowing coordination (BSC) and pulmonary function across research groups, but identify a reduction in overall swallowing efficiency in PD. Results from sensory assessments contributing to airway protection revealed that chemosensation was not different between age groups but base of tongue mechano-sensation was diminished in individuals with PD. Natural cough thresholds did not differ between young adults and elders but when asked to stifle coughing, elders were less able to do so compared to young adults (Chapter 7). For the first time, a reduction in mechano-reception at the base of tongue was recorded in individuals with PD (Chapter 8). These patients also demonstrated increased post swallow residual (Chapter 5), which offers an explanation for the complaint of globus in this population. These assessments highlight some compromise to sensory aspects of airway protection in PD. Overall, dysphagia had a negative impact on the quality of life of individuals with PD and even more as disease severity progresses (Chapter 9). Results from part two of the study looking at the effects of therapeutic interventions on airway protection revealed some unexpected findings. In chapter 10, results showed a reduction in pulmonary function when 'on' levodopa, but no differences in swallowing efficiency, BSC, or laryngopharyngeal chemo- and mechano-reception were observed. These results suggested a reduction in pulmonary function with levodopa without any increase in risk of airway protection compromise1. Unexpectedly and documented for the first time, the percentage of post swallow inspiration increased after LSVT (Chapter 11) but as with the levodopa study, this was also not accompanied by any apparent increase in aspiration risk. An increase in submental surface electromyography (sEMG) amplitude across all 5 participants may serve as a proxy measure of improvement in hyolaryngeal excursion. Finally, participants reported an overall improvement in social functioning and communication after LSVT. In conclusion, this study provided evidence that mechano-sensory aspect of airway protection is diminished in individuals with PD, possibly compromising airway protection. Patients not only demonstrated increased residue but the lack of sensation may prevent clearing or spontaneous multiple swallows. Overall, airway protection is maintained in ageing but swallowing efficiency declines in the presence of PD. This study contributes significantly to current research efforts in PD by expanding on existing reports regarding motor aspects of airway protection. Specifically, BSC, swallowing efficiency and evaluation of biomechanics using FEES research have never before been investigated exclusively in the PD population. Finally, the chemo- and mechano-sensation evaluated in this study are an important addition to the limited evidence that sensory impairment in individuals with PD potentially compromises airway protection. Results of the present study will serve as a platform upon which future studies may compare and expand.

The age structure of populations is an important and often unresolved factor in ecology and wildlife management. Parameters like onset of reproduction and senescence, reproductive success and survival rate are tightly correlated with age. Unfortunately, age information of wild animals is not easy to obtain, especially for birds, where few anatomical markers of age exist. Longitudinal age data from birds banded as chicks are rare, particularly in long lived species. Age estimation in such species would be extremely useful as their long life span typically indicates slow population growth and potentially the need for protection and conservation. Telomere length change has been suggested as a universal marker for ageing vertebrates and potentially other animals. This method, termed molecular ageing, is based on a shortening of telomeres with each cell division. In birds, the telomere length of erythrocytes has been reported to decline with age, as the founder cells (haematopoietic stem cells) divide to renew circulating red blood cells. I measured telomere length in kakapo, the world largest parrot and four other bird species (Buller’s albatross, kea, New Zealand robin and saddleback) using telomere restriction fragment analysis (TRF) to assess the potential for molecular ageing in these species. After providing an overview of methods to measure telomere length, I describe how one of them (TRF) measures telomere length by quantifying the size distribution of terminal restriction fragments using southern blot of in-gel hybridization (Chapter 2). Although TRF is currently the ‘gold standard’ to measure telomere length, it suffers from various technical problems that can compromise precision and accuracy of telomere length estimation. In addition, there are many variations of the protocol, complicating comparisons between publications. I focused on TRF analysis using a non-radioactive probe, because it does not require special precautions associated with handling and disposing of radioactive material and therefore is more suitable for ecology laboratories that typically do not have a strong molecular biology infrastructure. However, most of my findings can be applied to both, radioactive and nonradioactive TRF variants. I tested how sample storage, choice of restriction enzyme, gel Abstract II electrophoresis and choice of hybridization buffer can influence the results. Finally, I show how image analysis (e.g. background correction, gel calibration, formula to calculate telomere length and the analysis window) can not only change the magnitude of estimated telomere length, but also their correlation to each other. Based on these findings, I present and discuss an extensive list of methodological difficulties associated with TRF and present a protocol to obtain reliable and reproducible results. Using this optimized protocol, I then measured telomere length of 68 kakapo (Chapter 3). Almost half of the current kakapo population consists of birds that were captured as adults, hence only their minimum age is known (i.e. time from when they were found +5 years to reach adulthood). Although molecular ageing might not be able to predict chronological age accurately, as calibrated with minimum age of some birds, it should be able to compare relative age between birds. Recently, the oldest kakapo (Richard Henry) was found to show signs of reproductive senescence. The age (or telomere length) difference to Richard Henry could have been used to approximate the remaining reproductive time span for other birds. Unfortunately, there was no change of telomere length with age in cross sectional and longitudinal samples. Analysis of fitness data available for kakapo yielded correlations between telomere length and fledging success, but they were weak and disappeared when the most influential bird was excluded from analysis. The heavy management and small numbers of kakapo make conclusions about fitness and telomere length difficult and highly speculative. However, telomere length of mothers and their chicks were significantly correlated, a phenomena not previously observed in any bird. To test if the lack of telomere loss with age is specific to kakapo, I measured telomere length of one of its closest relatives: the kea (Chapter 4). Like kakapo, telomere length did not show any correlation with age. I then further assessed the usefulness of molecular ageing in birds using only chicks and very old birds to estimate the maximum TL range in an additional long lived (Buller’s albatross) and two shorter lived species (NZ robin and saddleback). In these Abstract III species, telomere length was on average higher in chicks than in adults. However, age matched individuals showed high variations in telomere length, such that age dependent and independent telomere length could not be distinguished. These data and published results from other bird species, coupled with the limitations of methodology I have identified (Chapter 2), indicate that molecular ageing does not work in most (if not all) birds in its current suggested form. Another way to measure telomere length is telomere Q-PCR, a real-time PCR based method. Measurement of the same kakapo samples with TRF and Q-PCR did not result in comparable results (Chapter 4). Through experimentation I found that differences in amplification efficiency between samples lead to unreliable estimation of telomere length using telomere Q-PCR. These differences were caused by inhibitors present in the samples. The problem of differential amplification efficiency in Q-PCR, while known, is largely ignored by the scientific community. Although some methods have been suggested to correct for differing efficiency, most of these introduce more error than they eliminate. I developed and applied an assay based on internal standard oligonucleotides that was able to corrected EDTA induced quantification errors of up to 70% with high precision and accuracy (Chapter 5). The method, however, failed when tested with other inhibitors commonly found in DNA samples extracted from blood (i.e. SDS, heparin, urea and FeCl3). PCR inhibition was highly selective in the probe-polymerase system I used, inhibiting amplification of genomic DNA, but not amplification of internal oligonucleotide or plasmid standards in the same reaction. Internal standards are a key feature of most diagnostic PCR assays to identify false negatives arising from amplification inhibition. The differential response to inhibition I identified greatly compromises the accuracy of these assays. Consequently, I strongly recommend that researchers using PCR assays with internal standards should verify that the target DNA and internal standard actually respond similarly to common inhibitors.

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Mobile data traffic is growing exponentially due to the popularization of smart phones, tablets and other data traffic appliances. One way of handling the increased data traffic is to deploy large antenna arrays at the base station, also known as Massive MIMO. In Massive MIMO, the base station having excessive number of transmit antennas, can achieve increased data rate by spatial-multiplexing terminals into the same time-frequency resource. This thesis investigates Massive MIMO in LTE in a single-cell deployment with up to 100 base station antennas. The benefits of more antennas are investigated with single-antenna terminals in a typical urban environment. The terminal transmitted sounding reference signals (SRS) are used at the base station to calculate channel state information (CSI) in order to generate an MRT precoder. With perfect CSI, the results showed that the expected terminal SINR depends on the antenna-terminal ratio. It was also showed that with spatial-multiplexed terminals and 100 base station antennas, the maximum cell throughput increased 13 times compared with no spatial-multiplexed terminals. Channel ageing causes inaccuracy in the CSI, the thesis showed that the variation in terminal SINR increased rapidly with less frequent SRS transmissions. When having moving terminals at 3 km/h, the difference between the 10th and 90th SINR percentile is 1 dB with an SRS transmission periodicity of 20 ms, and 17 dB with an SRS transmission periodicity of 80 ms. With 100 base station antennas and moving terminals at 3 km/h with an SRS periodicity of 20 ms, the maximum cell throughput decreased with 13% compared to when the base station has perfect CSI. The result showed that the maximum cell throughput scaled linearly with the number of base station antennas. It also showed that having the number of spatial-multiplexed terminals equal to the number of antennas is a reasonable assumption when maximizing the cell throughput.

This thesis is composed of an ethnography of the Women’s Running Network (WRN) – a non-elite women’s-only running group – and explores participant’s lived experiences of health and ageing (and the intersection of these) in this physical context. In-depth interviews (n = 25), inclusive of case studies (n = 3), with women between the ages of 29 and 66 allowed insight into the subjective contours of participant’s lives, and their particular biographical trajectories culminating in WRN participation. Several types of narrative analyses were applied to the emergent data, and results from these revealed insights into if, why, how, and when women engaged with health and ‘active ageing’ messages across the life course. Despite a prevalence of health knowledge, participants tended to report long periods of inactivity throughout their lives – citing the often documented barriers to physical activity such as a lack of time and caregiving responsibilities. However, a vast majority of participants also cited an utter lack of confidence with respect to physical activity, often stemming from highly influential poor early experiences. Embodying a perceived ‘non-sporting’ identity for as long as they had, they were foreclosed to the idea of physical activity despite simultaneously feeling pressure to participate. For many, it was particular life events - or ‘critical moments’ – that brought participation in physical activity to the forefront (i.e., birthdays, relationship issues, bereavement, and health scares). A consideration of these within this thesis explores the complex link that exists between health consciousness and action. In addition, alternative narratives about who could be a runner (within WRN advertising and by word of mouth) ‘hailed’ participants to reconsider their foreclosed narratives, by offering a ‘fun and non-competitive’ atmosphere for people ‘of all ages, sizes, and abilities’. Once pushed to action and within the WRN setting, participants described learning about themselves and their bodies, and thus developed the capacity to tell new stories. As such, through a narrative lens, this thesis introduces the stories that participants responded to (or not), and the stories that they used to tell, felt able to tell, and – in some cases – learned how to tell about health, about ageing, and about running/physical activity. Conclusions from this work have implications for both policy and practice, advocating for the necessity of comprehensive insight into people’s perceptions and lived experiences of (active) ageing within the context of life history, current life stage, and the everyday.

Astrocytes, the most abundant glial cell type in the brain, undergo a number of roles in brain physiology; among them, the energetic support of neurons is the best characterized. Contained within astrocytes is the brain’s obligate energy store, glycogen. Through glycogenolysis, glycogen, a storage form of glucose, is converted to pyruvate that is further reduced to lactate and transferred to neurons as an energy source via MCTs. Glycogen is a multi-branched polysaccharide synthesized from the glucose uptaken in astrocytes. It has been shown that glycogen accumulates with age and contributes to the physiological ageing process in the brain. In this study, we compared glycogen distribution between young adults and geriatric mice to understand the energy consumption of synaptic terminals during ageing using computational tools. We segmented and densely reconstructed neuropil and glycogen granules within six (three 4 month old old and three 24 month old) volumes of Layer 1 somatosensory cortex mice brains from FIB-SEM stacks, using a combination of semi-automated and manual tools, ilastik and TrakEM2. Finally, the 3D visualization software, Blender, was used to analyze the dataset using the DBSCAN and KDTree Nearest neighbor algorithms to study the distribution of glycogen granules compared to synapses, using a plugin that was developed for this purpose. The Nearest Neighbors and clustering results of 6 datasets show that glycogen clusters around excitatory synapses more than inhibitory synapses and that, in general, glycogen is found around axonal boutons more than dendritic spines. There was no significant accumulation of glycogen with ageing within our admittedly small dataset. However, there was a homogenization of glycogen distribution with age and that is consistent with published literature. We conclude that glycogen distribution in the brain is not a random process but follows a function distribution.