Amblyopia is the leading cause of monocular visual impairment in children. Therapy for amblyopia is extremely beneficial in some children but ineffective in others. It is critical that the reasons for this discrepancy are understood. Emerging evidence indicates that current clinical protocols for the diagnosis of amblyopia may not be sufficiently sensitive in identifying individuals who, on more detailed examination, exhibit subtle structural defects of the eye. Presently, the magnitude of this problem is unknown. The aim of this study was to establish the prevalence of subtle retinal/optic nerve head defects in eyes diagnosed with amblyopia, to distinguish between possible explanations for the origin of such defects and to investigate the relationship between quantitative measures of retinal structure, retinal nerve fibre layer thickness and optic nerve head dimensions. Using the imaging technique of Optical Coherence Tomography (OCT) retinal structure has been investigated in detail, following the visual pathway across the retina from the fovea, via the paramacular bundle to the optic disc, where peripapillary retinal nerve fibre thickness has been imaged and subjected to detailed measures along with optic disc size and shape. The study formed two phases, the first imaging the eyes of visually normal adults and children, comparing them to amblyopes, both adults and children who had completed their treatment. The second phase, a longitudinal study, investigated retinal structure of amblyopic children undertaking occlusion therapy for the first time. By relating pre-therapy quantitative measures to the visual outcome the second phase of the study aimed to examine whether OCT imaging could identify children achieving a poor final outcome. The results show a clear picture of inter-ocular symmetry structure in all individuals, visually normal and amblyopic. Optic disc characteristics revealed no structural abnormalities in amblyopes, in any of the measured parameters, nor was there any association between the level of visual acuity and the measured structure. At the fovea differences were shown to occur in the presence of amblyopia, with thickening of the fovea and reduction of the foveal pit depth. The structural changes were found to be both bilateral and symmetrical with the fellow eye also affected. In the longitudinal phase of the study these changes were demonstrated to a greater extent in children who ¿failed¿ to respond to treatment. This bilateral, symmetrical structural change found at the fovea, which has not been previously reported, cannot therefore be the primary cause of the visual loss which has been diagnosed as amblyopia.

<p>A detailed analysis of coupled cavity semiconductor lasers with asymmetric multiple quantum well (AMQW) active regions is presented in this thesis. The analysis involved design, fabrication, characterization, and simulation of these devices. Although the coupled cavity devices can be multi sectioned, the devices discussed in this thesis are two sectioned.</p><p> A below threshold model for an AMQW coupled cavity device is developed. Non-linear fits of the below threshold spectral data to that obtained from the model were used to extract optimized device parameters. These fits helped to create an understanding of the operation of the devices and paved the way for improved device performance. Optimized device parameters obtained from the below threshold model were later used as input parameters in the development of an above threshold model. This model verified the wavelength selection mechanism employed by coupled cavity diode lasers and predicted the longitudinal modes for sets of injection currents.</p><p> Optical coherence tomography (OCT) is an application where much interest has recently been drawn. The coupled cavity devices fabricated in this work applied with proper modulation of the injection currents and followed by subsequent time averaging have demonstrated short coherence length (-15 μm) and can be an excellent source for synthesized OCT. Rapid wavelength switching (-70 ns, the measurement was limited by detector response time) over the whole range has also been experimentally shown. Because of the high speed (relative to mechanical) wavelength switching ability, AMQW coupled cavity devices have the potential for applications requiring real time measurements including real time synthesized OCT.</p> / Thesis / Doctor of Philosophy (PhD)

Despite advancements in percutaneous coronary intervention, stents are still limited by a 2% annual rate of in-stent restenosis (ISR) related to neointimal (NI) tissue proliferation. Efforts to prevent ISR formation remain the focus of ongoing work. Adenosine (ADO) is a purine nucleoside with integral roles in vascular homeostasis, though it has limited clinical application. ADO signals primarily via four receptors with ADO receptor-A2B (ADOR-A2B) considered to play an integral role in vascular healing. Dipyridamole (DP) is a commercially approved therapy known to improve vascular events and modulate adenosine biology. Our objectives with this study included (i) assessing whether ADO could serve as a biomarker of cardiac events; (ii) determine if DP could mitigate NI formation in a pre-clinical stent model; and, (iii) quantify the mechanisms of DP-related vasculoprotection, specifically related to ADOR-A2B. We assessed the analytic and biologic variability of circulating ADO levels in humans and demonstrated that circulating ADO was not predictive of cardiac events at one year following invasive coronary angiography. We then assessed whether modulation of adenosine biology with DP had therapeutic efficacy in a pre-clinical model. Utilizing meta-analysis, we confirmed the sustained effects of DP on vascular patency rates in both pre-clinical and clinical studies. We refined a pre-clinical rabbit model of stent implantation with assessment of stent healing by intravascular optical coherence tomography – with excellent translation to clinical observations. We then assessed DP in a pre-clinical model, demonstrating reduction in ISR and improved stent healing with DP compared to control. Last, we sought to elucidate the mechanisms behind the observed DP effects, specifically related to ADOR-A2B. In vivo, DP therapy demonstrated reduced NI smooth muscle cell (SMC) content. In vitro assessment of DP demonstrated dose-dependent inhibition of SMC proliferation and migration with alteration of SMC phenotypic switching, while selective modulation of ADOR-A2B and ADOR-A2B knockdown support an ADOR-A2B-mediated component to the observed DP effects. Adenosine biology is integral to vascular homeostasis. In humans, circulating adenosine levels in humans are not predictive of one year cardiovascular events. However, DP may improve vascular healing post stent implantation and warrants clinical evaluation for stent healing. The observed DP benefits may, in part, stem from ADOR-A2B modulation. ADOR-A2B is a viable target for assessment of small molecule modulation as a novel therapeutic target to improve vascular outcomes.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24877号 / 医博第5011号 / 新制||医||1068(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川上 浩司, 教授 森田 智視, 教授 長船 健二 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Sensory adaptation to blur improves visual acuity under defocused conditions. This phenomenon has been successfully demonstrated using subjective measures of acuity and is known as blur adaptation. This study investigates aspects of the mechanism of blur adaptation in human vision using subjective and objective methods. Parafoveal visual acuity measured under defocused conditions demonstrates that blur adaptation is not limited to the fovea. The presence of the adaptive mechanism in the parafovea also suggests that the neural compensation that takes places under defocused conditions acts across a spatial range and is not limited to specific frequency bands. An evaluation of the contrast sensitivity function under defocus provides further evidence. Electrophysiological methods measure the effect of blur adaptation at the retina and at the visual cortex to provide objective evidence for the presence of the blur adaptation mechanism. Finally enhanced-depth imaging optical coherence tomography examines whether a period of prolonged defocus triggers any short-term changes in choroidal thickness in a similar manner to that reported in animal emmetropisation. / Engineering and Physical Sciences Research Council

Glaucoma is a leading cause of irreversible vision loss globally, and demands early and accurate diagnosis. OCT has become a key investigative technique in glaucoma, and, although it provides invaluable clinical support, detection of early glaucoma remains imperfect. Recent OCT developments enabled direct assessment of retinal nerve fibre bundle (RNFB) reflectance in en face OCT images. The technique has considerable potential in the assessment of glaucoma, yet it has limited clinical usability due to an incomplete understanding of RNFB features in healthy and glaucoma eyes and the lack of accepted methods to identify reflectance defects. This thesis aimed to better understand characteristics of RNFB reflectance in en face OCT imaging and to develop objective methods to extract defects in this domain. Structural and functional measures of glaucoma changes were collected in eyes with established glaucoma and age-similar controls. Results showed that the healthy configuration of RNFB varies across the retina and between different eyes. We developed a method for automated and objective examination of reflectivity changes in en face images. This method considers individual anatomy and varying RNFB configuration, and found more abnormalities than previous approaches. Measures of en face reflectance and conventional retinal nerve fibre layer thickness were strongly related. The agreement between changes of reflectance and visual function was moderate-to-good, and both testing domains presented concordant abnormalities in all tested eyes. Following further minimisation of artefacts in en face images, direct use of reflectance analysis or its combination with perimetry appear viable and with significant potential for clinical examination of glaucoma.

Second language (L2) writing is a subfield within the field of applied linguistics concerned with applying knowledge and insights from linguistics, psychology, and education to develop teaching approaches for those who need to acquire L2 writing skills for academic or work purposes (Belcher, 2012). Much research on L2 writers over the past five decades has been focused on students in university contexts (Ferris, 2018) in part because universities are often not equipped to meet students’ needs for academic writing support in writing courses (Cimasko & Reichelt, 2011; Kubota & Abels, 2006). One student need pertains to the learning of discourse organization to create coherent text. This issue is of particular concern to EFL undergraduates who often experience difficulty with organizational patterns when writing in English (Tang, 2012).In response to this student need, the current study investigated the effectiveness of the explicit teaching of coherence in EFL undergraduates’ research writing in English with a pre- and post-intervention embedded mixed-methods design of three study groups of Japanese undergraduate students. More specifically, the study involved two experimental groups—a process-genre group and process-writing group—and a comparison group. The teaching program for these three groups differed in the combination of classroom instruction (i.e., coherence-focused process-genre approach or process writing) and written teacher feedback (i.e., coherence-focused or meaning-focused) they received. A total of 36 third-year female undergraduate English majors participated in this study. Writing samples were collected at three points throughout one semester and analyzed based on three measures of writing coherence: reader-based logical development, reader-based cohesion, and text-based coherence. The reader-based measures of an analytic rubric were used by human raters in evaluating reader-based coherence in the writing samples. Rasch measurement was used to assess the rubric’s functioning via a Rasch principal components analysis (Linacre, 2019). In addition, the Rasch model was used to identify raters who were too lenient or too severe and calculate fair average measures of the ratings using Many-Facets Rasch analysis (Linacre, 2014). These ratings were then analyzed and investigated for changes across time and between groups. The text-based coherence measure for each writing sample was obtained via a form of textual analysis called topical structure analysis. Mixed-design ANOVAs were used to analyze the three measures to investigate statistical differences within-group and between-groups differences. In addition, a Pearson’s correlation analysis was conducted to investigate if raters’ assessment of logicality correlates with their assessment of cohesion usage in student samples of research writing. Results from the statistical analyses revealed that the process-genre group was the only group out of all three groups in this study to have made statistically significant improvements on coherence in their research writing during the course of study. To help explain the results of the statistical analyses, qualitative data collected from background questionnaires, rater’s questionnaires, reflective journals, and student interviews were coded and analyzed. The findings indicated that the process-genre group was able to develop coherence at the sentence, paragraph, and discourse levels. Further, a comparison of the results from both the reader-based and text-based perspectives of coherence suggested that coherence development achieved by the process-genre group (i.e., improvement in both logical development and cohesion) was due to the treatment they received as observations from their background questionnaire reflective journal responses and interview data suggested that they appeared to be unaware of the concept of coherence prior to the study. However, as the treatment started, they gradually acquired knowledge and skills for creating coherence, first at the sentence level, then at the paragraph level, and toward the end of the study, at the discourse level. The improvements made by the process-genre group appeared to be related to the changes observed in their perception of coherence throughout the treatment period. The qualitative findings indicated that their perceptions changed from a focus on the relevance of information included in their writing in the beginning of the treatment period to an expanded understanding of coherence as a genre-specific concept that is important in making their writing reader-friendly by using both local and global cohesion and coherence devices. As to the other two groups in this study, the qualitative findings from the background questionnaire responses and interview data suggested that unlike the process-genre group, the process writing group’s coherence development was limited to the sentence and paragraph levels, and that of the comparison group only at the sentence level. The fact that these two groups failed to develop their knowledge and skills in writing coherently at the discourse level might explain the non-significant statistical results for the within-group and between-group analyses conducted with those groups. In sum, the findings showed that the development of coherence in EFL undergraduate research writing is influenced by writing program design. Particularly, the program needs to explicitly teach coherence through a systematically designed curriculum that includes the teaching of both useful genre knowledge and skills for writing coherently. In addition to teaching the textual construction of coherence, because coherence is a reader-based concept, its crucial role in producing research writing that is logical in the eyes of readers also needs to be reinforced in the teacher feedback given to learners. Such a program where both the instruction and the teacher feedback are focused on form (i.e., coherence in research writing) enables learners to improve coherence in their writing as they progress through the drafting cycle of writing and revising in the program. / Teaching & Learning

Arbetsrelaterad känsla av sammanhang (KASAM), empowerment och psykosocial arbetsmiljö (PSAM) är väletablerade begrepp. Det finns begränsad forskning om deras inbördes relation, dock har tidigare forskning konstaterat att höga nivåer av KASAM och empowerment är relaterad till god upplevelse av anställdas PSAM. Studiens syfte var att undersöka relationen och variationen mellan PSAM, KASAM och empowerment. Detta besvarades genom fyra frågeställningar och tre hypoteser. I studien ingick 130 deltagare (74 kvinnor och 56 män). Datainsamlingen skedde på två separata arbetsplatser. Enkäten inkluderade fem bakgrundvariabler och tre skalor. Materialet analyserades med korrelationer och regressionsanalyser. Analyserna visade att KASAM och empowerment kompletterar varandra med att förklara variationen i PSAM. Korrelationerna indikerade att högre upplevelse av KASAM och empowerment är kopplade till en högre skattning av PSAM. Utöver detta korrelerade KASAM och empowerment med varandra. Slutsatsen som drogs var att arbetsplatser måste undersöka dessa tre delar tillsammans för att få en överblick över hur anställda upplever sin PSAM.

Syfte: Syftet med denna studie var att undersöka hur upplevd stress korrelerade med känsla av sammanhang och personlighetsdrag och vidare att även undersöka om känsla av sammanhang och personlighetsdrag kunde predicera upplevelsen av stress hos universitetsstudenter, i Sverige. Metod: Studien använde ett kvantitativt tillvägagångssätt och genomfördes utifrån ett bekvämlighetsurval och med en digital enkät (n=111). Mätinstrumenten i enkäten bestod avPSS-10, för att mäta upplevd stress, SOC-13 för att mäta känsla av sammanhang och TIPI, för att mäta personlighetsdrag. Korrelationsanalys genomfördes för att undersöka korrelationen mellan variablerna och multipel regressionsanalys genomfördes för att undersöka om känsla av sammanhang och personlighetsdrag kunde predicera stress. Resultat: Korrelationsanalysen visade att upplevd stress korrelerade negativt med känsla avsammanhang (r=-0.77, p&lt;.001) samt personlighetsdragen samvetsgrann (r=-0.32, p&lt;.001) och emotionell stabilitet (r=-0.62, p&lt;.001). Multipla regressionsanalysen visade att känsla avsammanhang och emotionell stabilitet predicerade nivåerna av upplevd stress (R2=0,68,p&lt;.001). Slutsats: Statistisk signifikant samband fanns mellan upplevd stress, känsla av sammanhang och personlighetsdrag. Framtida longitudinella studier skulle kunna utföras för att vidareundersöka relationen dem emellan. / Aim: The aim of this study was to examine how perceived stress correlated with sense of coherence and personality traits and further to examine whether sense of coherence and personality traits could predict the experience of stress in university students, in Sweden. Method: The study used a quantitative approach and was conducted based on a convenience sample and with a digital survey (n=111). The measuring instruments in the survey consisted of PSS-10, to measure perceived stress, SOC-13 to measure sense of coherence and TIPI, to measure personality traits. Correlations analysis was conducted to examine the relationship between the variables and multiple regression analysis was conducted to examine whether sense of coherence and personality traits could predict stress. Result: The correlation analysis showed that perceived stress correlated negatively with KASAM (r=-0.77, p&lt;.001) and the personality traits conscientiousness (r=-0.32, p&lt;.001) and emotional stability (r=-0.62, p&lt;.001). The multiple regression analysis showed that sense ofcoherence and emotional stability predicted the levels of perceived stress (R2=0,68, p&lt;.001). Conclusion: Statistically significant relationship where found between perceived stress, sense of coherence and personality traits. Future longitudinal studies may be conducted to further examine the relationship between them. / Nej

Retinitis pigmentosa (RP) is the most common form of inherited retinal degeneration, heterogenous in its clinical presentation and genetic cause. Understanding the short-term disease mechanisms is pivotal for the development of new therapies. Upcoming clinical trials will take genotype-agnostic approaches; therefore, a comprehensive analysis of progression that encompasses many genetic factors will be needed. In this 10-year retrospective cohort study, rates of progression were measured, structurally and functionally, in 85 RP patients seen at the Ottawa Eye Institute. Parameters examined were the ellipsoid zone (EZ) length on an optical coherence tomography (OCT) image, Humphrey and Goldmann visual fields (VF), and full-field and multifocal electroretinograms (ERGs). RP is revealed to have a 1st order exponential decay pattern of loss, with mean rates of decline of 7.65 %/year for ellipsoid zone (EZ) length, 6.35%/year, 4.39%/year, and 1.57%/year for the Humphrey VF 30-2, 24-2, and 10-2 mean deviation (MD) respectively, and 5.22%/year, 7.77%/year, 6.77%/year, 6.80%/year, and 12.45%/year for Goldmann V4e, III4e, I4e, I3e, and I2e isopter lengths, respectively. In cases where different diagnostic tests were conducted within 3 months of each other, the data was analysed to determine if there was a positive correlation between the diagnostic tests. Ellipsoid zone length and Humphrey 24-2 mean deviation exhibited the strongest association with a coefficient of 0.99. The study reveals structural and functional changes in advanced retinitis pigmentosa and presents a protocol for assessing short-term progression.