One in nine North American women will be diagnosed with breast cancer in their lifetime and most will receive chemotherapy as part of their treatment. Although advances in treatment have increased survivorship, some research suggests chemotherapy results in cognitive deficits in a subset of recipients, a condition known as chemo-fog, thereby compromising quality of life. However, inconsistencies in methodology and neuropsychological assessment have complicated comparison of findings. The first objective of this thesis was to review the methodological issues with an emphasis on the quantitative techniques typically employed. A comparison of group and individual based analyses found negligible effects for both univariate and multivariate approaches while individual based analyses identified severe declines in function in a subset of participants. A standardized-regression based (SRB) approach was recommended as the method of choice. Furthermore, it was recommended that the number of tests be limited since comprehensive batteries can complicate identification due to increased risk of misclassification. Therefore, the second goal of the thesis was to evaluate the sensitivity of a reduced battery to the declines associated with chemo-fog. A comprehensive neuropsychological battery comprising 23 tests was compared to a subset of nine tests. SRB analyses demonstrated that a more selective battery was equally useful and may be appropriate for identification of chemo-fog. Given the variability in the composition of neuropsychological test batteries, the final aim of this thesis was to compare the structure of the theoretical cognitive domains with ones identified through exploratory factor analyses (principle axis factoring) to evaluate the convergence between the two. The results demonstrated there is statistical support for the conceptual framework that underlies the composition of the domains. The contributions of this thesis include providing methodological guidelines for those conducting future research in this area to ensure that results are comparable across studies and are meaningful, and evaluating the utility of a screening battery to facilitate identification of chemo-fog. In addition, it was demonstrated that despite the lack of professional guidelines informing the selection and construction of neuropsychological test batteries, there is statistical evidence to support the practice of grouping tests into domains based on theoretical grounds.

This dissertation describes separate but related studies that explore the prospective memory abilities of older adults and individuals with Mild Cognitive Impairment/Early Alzheimer’s disease. Prospective memory (PM) refers to the type of memory utilized to execute planned actions in accordance with a specific event. PM is critical to maintaining functional independence in older adults, as it can refer to such basic acts as remembering to turn off a stove or taking one’s medication. Research suggests PM abilities decline within normal aging and to a greater extent in Mild Cognitive Impairment (MCI) and early Alzheimer’s Disease (AD). Together, the studies assessed and compared the PM abilities across healthy younger and older adults, individuals with MCI, and individuals with early AD while exploring two major theories that seek to explain PM retrieval. The preparatory attentional and memory process theory of PM (PAM) assumes that PM retrieval requires resource-demanding preparatory attentional processes, whereas the Dynamic Multiprocess theory (DMPT) assumes that retrieval can also occur spontaneously (Scullin, McDaniel, & Shelton, 2013; Smith & Bayen, 2006). Study 1 used a novel laboratory PM task in which the focality and the frequency of PM cues were manipulated to compare the PM abilities of cognitively healthy younger and older adults. The results revealed significant differences in the patterns of performance between the younger and older adults based on the focality and frequency of cues which indicated different attentional allocation strategies. Study 2 examined the impact of cognitive impairment on PM abilities by using the same paradigm to compare the performance of cognitively healthy older adults to individuals with MCI and early AD. The results again revealed significant differences in the patterns of performance which indicated that these groups may have used different strategies of attentional allocation depending on the focality and cue frequency. Taken together, the findings in Studies 1 and 2 were mixed with respect to the predictions of the DMPT and PAM. The MCI group, in particular, demonstrated a unique performance profile that suggests the neuropathophysiological changes associated with this diagnosis may lead to the reliance on different PM retrieval processes compared to healthy older adults. Finally, Study 3 explored the use of a more naturalistic and ecologically valid PM task to compare the PM performance of individuals with MCI and early AD to healthy older adults without cognitive impairment. The results showed that, after taking the learning and retrospective memory scores into account, the significant differences between groups in PM accuracy on this task can mostly be accounted for by these factors. Nevertheless, the AD group was found to display significantly lower PM accuracy with event-based cues with a weak association between cue and action compared to the older adult and MCI groups after controlling for these factors. These findings provide valuable theoretical, methodological, and clinical contributions which will be discussed.

The thesis is concerned with prudence principle in accounting - especially with provisions and impairment of assets. The thesis focuses on comparison of IAS/IFRS requirements and the czech legislation.

The main goal of this thesis is to create a comprehensive view of the measurement of assets in accordance with International Financial Reporting Standards with closer focus on the impaiment tests of assets in accordance with IAS 36 Impairment of Assets. The thesis is divided into several parts the first of which is general and deals with the definition of assets, the conditions for their dislosure in the statement of financial position and methods of their valuation. This part is followed by the third chapter, which at first approaches the valuation models applicable on current and non-current assets, which are excluded from the scope of IAS 36, and then describes the principles of impairment tests of individual assets. The fourth chapter deals with impairment tests of cash-generation units, including goodwill and the allocation of corporate assets. The last part of this thesis contains examples from real financial statements, aim of which is to approach demands of IAS 36 concerning disclosure.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22732号 / 医博第4650号 / 新制||医||1046(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 髙橋 良輔, 教授 中山 健夫, 教授 川上 浩司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The purpose of my study is to investigate the treatment of individuals with a visual impairment in their work and studies based on constructs of femininity and masculinity. The method used in this study is qualitative, and it is a study based on interviews in which 7 informants with a visual impairment who have been interviewed as it is their perceived experiences that are the focus area of the study. The results that I have obtained in my study are that people with a visual impairment are treated differently by the environment and it depends on the gender to which one belongs, and in this study I have also concluded that the environmental assessments of the ability to work and learning ability of the visually impaired vary depending on the gender. This study shows how people with a visual impairment are assessed on the basis of their visual impairment, and not on the basis of their qualifications or competences in the work they have applied for or are working with. However, as these people become marginalized in the labor market, it is difficult for them to become involved in society, based on the perspective of the visually impaired, you feel that the environment assesses one's ability to work or learning ability before you even have the opportunity to show what you are able to do. This is assessed on the basis of the ignorance, fears and misunderstandings that society likes to attach to people with a visual impairment. / <p>2021-06-16</p>

京都大学 / 新制・課程博士 / 博士(人間健康科学) / 甲第23129号 / 人健博第91号 / 新制||人健||6(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 澤本 伸克, 教授 十一 元三, 教授 髙橋 良輔 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

BACKGROUND: It has long been accepted that the environment we experience can impact our well-being; throughout recorded history, the greatest prevalence and severity of disease has been experienced by marginalized and underserved populations. However, the translation of such nontangible influences into biological changes in our health has been elusive until the recent advent of epigenetic studies. Modifications outside of the genome play a critical role in regulating transcription as well as subsequent gene expression without altering DNA sequencing by controlling the accessibility of the DNA for interaction with key initiation proteins and enzymes. These modifications, which include DNA methylation, histone acetylation, and small noncoding microRNA regulation, have increasingly been found to have a fluid, adaptive response to experiences throughout life. Based on the literature supporting societal stressors negatively impacting neurologic outcome, as well as elucidating an association between epigenetic changes and adverse neurologic outcome, we hypothesize that alterations in CpG methylation sites associated with socioeconomic adversity will also be correlated with the incidence of Neurodevelopmental Disorders. METHODS: 889 of the 1,506 neonates initially recruited from 14 medical centers throughout the United States at their time of birth qualified to participate in this study. Placental samples were taken immediately following delivery and neonatal blood samples were taken within the first month of life. Children that survived were followed at 2 years old and 10 years old to evaluate for the presence of four possible Neurodevelopmental Disorders: cognitive impairment, Cerebral Palsy, Autism Spectrum Disorder, and epilepsy. Taking this data as well as demographic information into consideration, the entire cohort included in this study was first evaluated for aberrant methylation levels at 33 CpG sites previously associated with socioeconomic adversity to analyze the degree of significant correlation between altered methylation status and Neurodevelopmental Disorder prevalence. A secondary Epigenome-Wide Association Study was conducted for each of our 889 participants to pinpoint significant changes in CpG methylation in order to evaluate the relationship between altered methylation of particular genes and incidence of Neurodevelopmental Disorders. Taking the previous finding that cognitive impairment imposes a greater burden on both the individual and society than non-cognitive impairment into consideration, both analyses were categorized based on this measure of impairment severity: No Impairment, Non-Cognitive Impairment (diagnosed with Cerebral Palsy, Autism Spectrum Disorder, and/or epilepsy without cognitive deficit), and Cognitive Impairment (cognitive deficit with or without other neurodevelopmental disorders present). RESULTS: Primary analysis of the 33 CpG sites previously associated with socioeconomic adversity did not reveal any significant associations with Non-Cognitive or Cognitive Impairment. However, cg15519318 and cg10613063 (located in the PCCB gene) were marginally associated with Non-Cognitive Impairment while cg02765535 (located in the NTN4 gene) was marginally associated with Cognitive Impairment. Secondary analysis of the entire epigenome found 4 CpG sites significantly associated with Non-Cognitive Impairment (cg07322235, cg13592565, cg13723879, and cg24387818) as well as 4 CpG sites significantly associated with Cognitive Impairment (cg23081580, cg14134658, cg00762003, and cg08546514). DISCUSSION: We were not able to define a significant relationship between the CpG methylation sites related to socioeconomic adversity and adverse neurodevelopmental outcomes. This could stem from several causes, including insufficient power as well as limiting our evaluation of the extensive list of environmental influences to the four measures of societal stress focused on in this study (low educational attainment, single relationship status, public health insurance, and receiving supplemental nutrition assistance). Investigating the epigenome for differential methylation that was significantly associated with the incidence of Neurodevelopmental Disorders identified CpGs associated with several important genes, including genes coding for Neuregulin-3 (NRG3) and Premature Ovarian Failure Actin Binding Protein 1B (POF1B) region with Non-Cognitive Impairment as well as genes coding for Six-Transmembrane Epithelial Antigen of Prostate 2 Metalloreductase (STEAP2), Ly1 Antibody Reactive (LYAR), 1-Acylglycerol-3-Phosphate O-Acyltransferase 3 (AGPAT3), and Ninein-like protein (NINL) with Cognitive Impairment.

Δ9-Tetrahydrocannabinol (THC) is the most psychoactive substance out of the over 80 active cannabinoids. Due to its psychoactive and impairing properties, detection and quantitation is important to determine impairment levels of individuals. With an increased use of recreational marijuana, the risk of Driving Under the Influence of Drugs (DUID) is steadily increasing. Current legislation outlaws driving under the influence of Marijuana however there exists limitations with current methods of detection of drug analyte. Δ9-Tetrahydrocannabinol, 11-Hydroxy- THC, and 11-nor-carboxy-THC, were used in detection because these analytes are produced in the metabolism of THC. Since THC is very lipid soluble, it is present in lipid rich environments in the body. Due to the lipid rich nature of meibomian fluid, a component of tears, and the presence of Fatty Acid Binding Protein (5) FAPB5, a protein known to bind to cannabinoids, tear fluid could be used as a less-invasive biological matrix to test for the presence of THC and its metabolites. This project optimized a collection of tear fluid, along with a simple buffer extraction, to create a method suitable for direct injection using LC-MS/MS. Collection was completed by BVI Weck-Cel® Sterile Cellulose strips, measuring approximately 2 x 20 mm, and placed in Thompson eXtreme PVDF 0.2 𝜇m, pre-slit, red cap, filter vials containing Quantisal buffer solution for extraction. All analysis and calibrations were completed with fortified matrix standards with concentrations ranging from 0.25 - 250 ng/mL. Validation was consistent with American Academy of Forensic Sciences Academy Standards Board (ASB) Standards of Forensic Toxicology Standard 036, First Edition 2018. Tear samples were collected from volunteer patients according to Institutional Review Board (IRB) standards before and after administration of Marijuana. Samples were collected approximately 30 minutes post administration in order to capture tears when the analyte is most potent in the body. Samples and calibration standards were analyzed using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) with the QSight® 220 CR LC-MS/MS and the Halo® C18 3.0x50 mm (2.7 µm) column. Limit of Detection (LOD) and Limit of Quantitation (LOQ) for THC was calculated at 0.25 ng/mL. Limit of Detection of THCOOH was detected at 0.25 ng/mL and Limit of Quantitation was calculated at 1 ng/mL. Upon analysis of Patient Samples, it was determined that THC and metabolites could be detected and quantitated in tear fluid. However, it is noted that insufficient sample volume in collection of this type of sample is an issue that leads to poor quantitation and should be optimized in future research.

Individuals with mild neurocognitive disorder complete many activities of daily living independently; however, they may require the use of compensatory strategies while performing everyday tasks. Compensatory strategies, such as external memory aids, incorporate a strengths-based approach to enhance the functional needs of individuals. Although external memory aids have a strong evidence-base, limited assessment tools and interventions are available to facilitate the development of individualized treatment plans that promote sustained strategy use. To better support the everyday needs of individuals with mild neurocognitive disorder and to inform clinicians who are developing interventions, the current dissertation includes four paper that examine a functional framework for external memory aid assessment and intervention. The first paper examined a group intervention teaching three types of external memory aids on functional strategy use, perceived strategy use, and cognitive skills. The second paper identified individual preferences for experiences with external memory aids during and following intervention. The third paper examined individual changes in functional and perceived strategy use following a group-based intervention teaching external memory aids. Lastly, the fourth paper examined the content validity and internal structure of the Functional External Memory Aid Tool: a measure that explores external memory aid use with simulated everyday tasks. By understanding the weaknesses in currently used assessment and intervention practices and the unique preferences of clients, this multi-manuscript dissertation aims to enhance the immediate and long-term needs of individuals with mild neurocognitive disorder.