Alzheimer's disease~(AD) is the most frequent neurodegenerative dementia and a growing health problem. Early and accurate diagnosis and prediction of AD is crucial because treatment may be most efficacious if introduced as early as possible. Neuropsychological testing, which is clinically used, sometimes fails to recognize probable dementia, especially to recognize the disease at an early time point such as the mild cognitive impairment~(MCI), which is the prodromal stage of AD. Recently, there has been a realization that magnetic resonance imaging~(MRI) may help diagnoses of AD and MCI. In this dissertation, we introduce an MRI-analysis based algorithm to help diagnose the illness before irreversible neuronal loss has set in, and to help detect brain changes between MCI patients who may convert and may not convert to AD. Given a set of brain MR images, the algorithm first calculates the distance between each pair of images via a registration process. Then images are projected from a high dimensional Euclidean space to a low dimensional Euclidean subspace based on the calculated distances, with a dimension reduction method. Finally classical supervised classification approaches are employed to assign images to appropriate groups in the low dimensional space. The classification accuracy rates we obtained in our experiments are higher than, or at least comparable to, those reported in recently published papers. Moreover, this algorithm can be extended to explore the pathology distribution of AD. Exploring the distribution of AD pathology is of great importance to reveal AD related regional atrophy at specific stages of the disease and provide insight into longitudinal sequence of disease progression. Calculating distances between different brain structures produces different classification accuracy. Those structures yielding higher classification accuracy are considered as pathological regions. Our experimental results on pathology localization are also compared with the reproduced results using other existing popular algorithms; the observations are consistent. / Ph. D.

This study explores experiential access to outdoor environments. This qualitative thesis presents the results of open-ended interviews with four people who have severe visual impairment. The interviews gathered information about the participants leisure activities in outdoor settings. The purpose of the study was to discover the factors in the environment that contribute to a positive recreation experience for people with visual impairment. Experiential qualities of the environment for both people who are sighted and those who are blind were compared through the analysis of eight contemporary authors' writings related to environmental understanding and the transcripts of the four interviews. The overlap of experience in outdoor environments between these two user groups was explored. Two areas of significant influence on the participants' experience was discovered; (a) wayfinding and making sense, and (b) affective response. The specific factors in the environment that influenced the quality of experience for these participants, other than those that contribute to making sense, were found to include: (a) interaction with nature, (b) awareness of enclosure & openness of the setting, (c) intellectual and physical stimulation and challenge, and (d) direct physical interaction with the surrounding environment. This study provides some of the specific benefits and advantages of incorporation of multi-sensory stimulation in design for people of all abilities. / Master of Landscape Architecture

The concept of resilience, which indicates people's capability of using resources in difficult circumstances in order to reduce or prevent negative effects and achieve positive outcomes, has given a new perspective to the scientific literature on the experience of late-life memory loss and the experience of caring for persons with memory loss. The current research was guided by incorporation of resilience into the stress process model for assessing personal and caregiver burden associated with mild and more severe memory loss. I conducted two studies to investigate the association of protective factors with the well-being of people with dementia or mild cognitive impairment and their caregivers. The first study focused on the well-being of older persons with dementia (PwDs). I employed data from a large national sample of older adults to examine how the perceived social cohesion of neighborhoods affects quality of life among people with and without cognitive impairment in conjunction with their engagement in valued leisure activities. Findings revealed that, regardless of cognitive health status, all participants who perceived high neighborhood social cohesion reported better quality of life along with more participation in valued activities. However, PwDs reported significantly lower perceived neighborhood social cohesion, less involvement in valued activities, and poorer quality of life than persons without cognitive impairment. The second study focused on the well-being of caregivers for older persons with mild cognitive impairment (PwMCIs). I used dyadic data from families dealing with mild cognitive impairment to examine how well-being of caregivers for PwMCIs differed according to whether PwMCI-caregiver dyads had similar or different perceptions of the PwMCIs' cognitive impairment severity. Caregivers reported lower caregiving burden when they and PwMCIs had a similar cognitive impairment representation, or when caregivers rated the PwMCIs’ cognitive functioning more positively than the PwMCIs rated themselves. Also, PwMCIs’ and caregivers' perceptions, and their concordance or discrepancy in those perceptions, varied across the multiple domains related to MCI symptoms. These findings demonstrate that care dyads' perception of MCI-related deficits is not a unitary construct, and that the context of PwMCIs’ and caregivers’ dyadic illness appraisals is significantly associated with the caregivers' well-being. Taken together, the results of these two studies illustrate the value of considering resilience processes in people with cognitive impairment and their caregivers. Examining dimensions of resilience, in association with assessment of the intersecting effects of personal, interpersonal, and environmental factors, provides additional information about the effects of cognitive impairment on older adults’ well-being and the effects of assisting someone with cognitive impairment on caregiver well-being. / Ph. D. / Resilience indicates people's ability to successfully adapt to or bounce back from life adversity by using personal, social, and environmental resources. Resilience helps explain what makes some people with dementia and their caregivers tolerant of changes in memory functioning and able to adapt to difficulties associated with dementia. I conducted two studies to investigate the role of protective resources in buffering negative effects of memory loss on people with dementia and their caregivers. The first study compared people with and without dementia to find out how their sense of belonging to the community and their participation in valued leisure activities influenced their quality of life. Regardless of whether they had memory loss or not, all the people with a stronger sense of belonging in the community participated in more leisure and valued activities and, in turn, had better quality of life. However, compared to cognitively healthy people, those with dementia had lower sense of belonging, less participation in leisure activities, and poorer quality of life. These findings indicate that people with dementia may feel excluded from their community and experience barriers to participation in valued activities. Nevertheless, feeling that one belongs in the neighborhood and participating in valued leisure activities is important for well-being of older adults both with and without cognitive impairment. The second study examined how the well-being of caregivers for persons with mild cognitive impairment (MCI) differed according to whether caregivers and their care recipients had similar or different views on the care recipients’ memory problems. When they both had similar views or the caregivers had a more positive view than their care recipients did, the caregivers reported higher well-being. This finding suggests that some caregivers for people with MCI understand how the person with MCI views their own memory loss, and others either are not aware of all the memory loss symptoms or choose to ignore some of them. In either case, these caregivers feel less burdened than those who think their loved one’s symptoms are worse than the person with memory loss believes. Support for these caregivers is needed to help them cope better with the memory loss in their loved one. The results from these two studies provided valuable evidence about resilience in older adults facing memory loss and their caregivers. Being resilient can help people with dementia and their caregivers manage or overcome the difficulties associated with dementia.

Architecturally, my thesis project is a new type of design for children who have visual impairments. Most of the children who have visual impairments need more attention to receive a full education. With a proper education they will be able to start living by themselves without any assistance. I decided to design a school which would support the needs of the children and the aspirations of their parents; a place of safety and ambition that would free instructors and inspire the children. Then, I began to seek an architectural site program where I could locate my design. Old town Alexandria is an excellent location for the planned education center. Old town has its own urban context with boundaries like  the Potomac River,  trees, old railroad ways,  a  tunnel,  and other landmarks  like churches,  libraries, museums,  etc.  The children  in  the education  center  have  an  opportunity  to  learn  more  and  show  their  life  skills  easily  in  the  old town.  Also the site selection and location was important due to the history of the town, easy transportation and connections with surroundings, being right next to the Potomac River and minutes away from the Washington DC. / Master of Architecture / As far as I remember, what do we understand by visual impairments? This disability is not just limitations for a few people; actually it is a part of human life which everyone would experience at some point, temporarily or permanently. You might wonder what disabilities have in common with architectural writing, but isn’t architecture for human comfort? And clearly what does architecture & design for the disabled stand for? However, education is important because it’s the base of our life. Disability (student who has autism, physical disability or down syndrome) is one of the problems which exist in all countries of the world. Of course, hundreds of millions of people with special needs don’t have opportunities and resources to fulfill their basic human. Designing an inclusive environment in schools is the best possible option to enroll maximum number of children with disability in education. Therefore, it is an environment where they can receive real attention, the right support, specialist attention as well as excellent education from primary to secondary education, side by side with their classmates.

No / Within the academic career literature, disabled academics are under-researched, despite calls for career theory development through the exploration of marginalized groups' career experiences and the boundaries which shape these experiences. Here, boundaries refer to the symbolic resources which become reified to construct social boundaries shaping what is and is not possible in career contexts. This article contributes to the advancement of academic career theory by enabling insights into impairment effects as an embodied career boundary for disabled academics and outlining how experiences of impairment effects and disabled academics' agency are entangled with their career context and organizational members' responses. Impairment effects shape career choices and opportunities, by being negated, and/or influencing expectations of employers to provide inclusive contexts which acknowledge impairment effects as a legitimate organizing principle. However this recognition of impairment as a legitimate organizing principle is not always reciprocated, with implications for disabled academics' careers.

Yes / Importance: Myopia is a leading cause of untreatable visual impairment and is increasing in prevalence worldwide. Interventions for slowing childhood myopia progression have shown success in randomized clinical trials; hence, there is a need to identify which children would benefit most from treatment intervention. Objectives: To examine whether genetic information alone can identify children at risk of myopia development and whether including a child’s genetic predisposition to educational attainment is associated with improved genetic prediction of the risk of myopia. Design, Setting, and Participants: Meta-analysis of 3 genome-wide association studies (GWAS) including a total of 711 984 individuals. These were a published GWAS for educational attainment and 2 GWAS for refractive error in the UK Biobank, which is a multisite cohort study that recruited participants between January 2006 and October 2010. A polygenic risk score was applied in a population-based validation sample examined between September 1998 and September 2000 (Avon Longitudinal Study of Parents and Children [ALSPAC] mothers). Data analysis was performed from February 2018 to May 2019. Main Outcomes and Measures: The primary outcome was the area under the receiver operating characteristic curve (AUROC) in analyses for predicting myopia, using noncycloplegic autorefraction measurements for myopia severity levels of less than or equal to −0.75 diopter (D) (any), less than or equal to -3.00 D (moderate), or less than or equal to −5.00 D (high). The predictor variable was a polygenic risk score (PRS) derived from genome-wide association study data for refractive error (n = 95 619), age of onset of spectacle wear (n = 287 448), and educational attainment (n = 328 917). Results: A total of 383 067 adults aged 40 to 69 years from the UK Biobank were included in the new GWAS analyses. The PRS was evaluated in 1516 adults aged 24 to 51 years from the ALSPAC mothers cohort. The PRS had an AUROC of 0.67 (95% CI, 0.65-0.70) for myopia, 0.75 (95% CI, 0.70-0.79) for moderate myopia, and 0.73 (95% CI, 0.66-0.80) for high myopia. Inclusion in the PRS of information associated with genetic predisposition to educational attainment marginally improved the AUROC for myopia (AUROC, 0.674 vs 0.668; P = .02), but not those for moderate and high myopia. Individuals with a PRS in the top 10% were at 6.1-fold higher risk (95% CI, 3.4–10.9) of high myopia. Conclusions and Relevance: A personalized medicine approach may be feasible for detecting very young children at risk of myopia. However, accuracy must improve further to merit uptake in clinical practice; currently, cycloplegic autorefraction remains a better indicator of myopia risk (AUROC, 0.87). / PhD studentship grant from the College of Optometrists (Drs Guggenheim and Williams; supporting Mr Mojarrad) entitled Genetic prediction of individuals at-risk for myopia development) and National Institute for Health Research (NIHR) Senior Research Fellowship award SRF-2015-08-005 (Dr Williams). The UK Medical Research Council and Wellcome grant 102215/2/13/2 and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was conducted using the UK Biobank Resource (application 17351). The UK Biobank was established by the Wellcome Trust, the UK Medical Research Council, the Department for Health (London, England), the Scottish government (Edinburgh, Scotland), and the Northwest Regional Development Agency (Warrington, England). It also received funding from the Welsh Assembly Government (Cardiff, Wales), the British Heart Foundation, and Diabetes UK.

Yes / Unlike many other sports, Rugby Union has not permitted players to wear spectacles or eye protection. With an industrial partner, World Rugby developed goggles suitable for use while playing rugby for the purposes of growing participation amongst those that need to wear corrective lenses. This study reports on the profile and experiences of goggle wearers. 387 players received the goggles. Data were obtained from 188 (49 %) using an online, 75-item questionnaire. 87 % “strongly agreed/agreed” that goggles are beneficial and 75 % are happy with goggle performance. Common problems reported by 49.7 and 32.6 % of respondents were issues with fogging-up and getting dirty. 15 (8 %) players stopped wearing the goggles because of fogging-up, limits to peripheral vision and poor comfort/fit. Injuries were reported in 3 % of respondents. In none of these cases did the player stop wearing the goggles. From the positive experience of players in the trial, the goggles were adopted into the Laws of the game on July 1, 2019. As the need to correct vision with spectacles is common, and contact lenses are not worn by 80 % + of spectacle wearers, the new Rugby goggles will widen participation for those that need to wear refractive correction, or have an existing/increased risk of uniocular visual impairment.

Yes / THIS PAPER INVESTIGATES physical impairment and disability in the c 5th to 6th centuries ad in England through a combination of osteological and funerary analyses. A total of 1,261 individuals, 33 of whom had osteologically identifiable physical impairment, from nine early medieval cemeteries were included. The funerary data for all individuals in each cemetery was collected, and the individuals with physical impairment were analysed palaeopathologically. The burial treatment of individuals with and without physical impairment was compared both quantitatively and qualitatively, and patterns within and between cemeteries were explored to investigate contemporary perceptions and understandings of impairment and disability. The results suggest that some people with physical impairment and potential disability were buried with treatment that was arguably positive, while others were buried with treatment that was either normative or potentially negative. This suggests that, in the same way as the rest of the community, individuals with physical impairment and potential disability had a variety of identities (that may or may not have been influenced by their impairment or disability) and could occupy different social spaces/statuses.

Glaucoma is a degenerative disease that contributes greatly to vision loss and blindness worldwide. There are several treatments that focus on alleviating its symptoms, but few address the underlying pathophysiology, the blockage of aqueous outflow, and the onset of neuroretinal damage. Novel drugs under investigation have aimed to address this deficiency. Two of these Rho kinase inhibitors have been approved by national health agencies, and several are in clinical trials. This work investigates the promise of inhibitors of the Rho kinase signaling pathway to treat primary open-angle glaucoma.

This work identifies and describes pathological skeletal changes associated with and attributable to acquired syphilis and which potentially caused functional impairment within eleven skeletal individuals recovered from five industrial-era London cemeteries. In eight (72.73%), functional impairment was likely or very likely, based on type and distribution of lesions across their skeleton. These impairments likely impacted the individuals’ ability to engage in various forms of physical activity, potentially limiting their economic potential. These results expand our still highly limited understanding of syphilis’s functional impacts within past populations, especially within industrial-era societies, querying longstanding characterizations of tertiary gummatous involvement as benign, while encouraging paleopathological investigations of the functional impacts of syphilis in past populations in which the disease was endemic, such as industrial-era England. Further, with syphilis rates on the rise globally, this information may be informative prognostically for present-day clinical cases of primary to tertiary stage undiagnosed and/or untreated syphilis.