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Screening is the first step in identifying and treating alcohol-related problems among the senior population. This study was designed with two purposes. The first was to cross-validate the Senior Alcohol Misuse Indicator (SAMI) with two commonly used screening tools - the CAGE and the Shortened Michigan Alcoholism Screening Test – Geriatric version (SMAST-G). The second purpose was to examine the feasibility of using these tools within a front-line health care worker’s clinical protocol. The effectiveness of each screening tool was assessed by calculating the sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) for each screening tool with a sample of seniors recruited from clinical and community sources (N=87). Participants were classified into different types of drinker with a structured clinical interview (i.e., the Structured Clinical Interview for the DSM-IV and a medical history, including medication list). Seven problem drinkers, 36 at-risk drinkers, 25 non-problem drinkers, and 19 non-drinkers were identified. Among the three screening tools, the SAMI had the highest sensitivity (83.72%) in identifying at-risk drinkers and problems drinkers and best overall performance with the greatest AUROC (0.710), whereas the SMAST-G had the highest specificity (95.45%) in ruling out an alcohol-related problem among participants classified as non-problem drinkers and non-drinkers. Six outreach mental health care workers tested each screening tool at least three times with their senior clientele and rated each tool on a number of characteristics. An ANOVA and post-hoc analyses using the Least Significant Difference (LSD) compared these ratings among the three screening tools. The SMAST-G and CAGE were cited as the easiest to score (p=0.002), while the SMAST-G was cited as the screening tool providing the most clinical information (p=0.047) and the most comprehensive (p=0.019) of the three tools. These results point to the overall effectiveness of the SAMI and the user-friendliness of the SMAST-G as appropriate screening tools for identifying alcohol-related problems among the senior population. Future studies may further examine these two screening tools among as-yet-untested clinical populations (i.e., geriatric mental health outreach patients, cognitively impaired, collateral informants) and how to improve screening tool usage among health care providers. / Thesis (Ph.D, Psychology) -- Queen's University, 2013-08-23 15:11:13.165

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Class of 2010 Abstract / OBJECTIVES: This is a selective systematic review of the methods used to monitor for the ocular adverse effects of chronic hydroxychloroquine use. This was done to describe the screening methods for detecting retinal toxicity and the recommendations for early detection of hydroxychloroquine associated retinopathy. METHODS: A literature search of OVID-MEDLINE and the Evidence Based Medicine (EBM) search database in the AHSL website were performed for the date range October 1999 to October 2009. Articles were selected based on content related to our purpose statement. Each article must have had at least one or more ophthalmic screening test including: fundus photography, Amsler grid, perimetry, color vision, and multifocal electroretinography. RESULTS: The search results returned a total of 67 articles. A total of twelve articles were selected for review. A total of 959 human subjects were studied and 22 patients had reported retinal changes attributed to hydroxychloroquine. Nine of the eleven studies that included mfERG recommended this specific test for monitoring for hydroxychloroquine induced retinopathy. Only six of the studies recommended the frequency of testing. The most common recommendation was to test at baseline and then at least annually. CONCLUSIONS: The results suggest the mfERG is the most sensitive and objective exam for early documentation of toxic retinopathy. In addition baseline and annual testing was suggested most often. The data also suggest that high risk patients be followed more closely as the most severe and irreversible damage occurs in this population.

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Universelles Neugeborenen Hörscreening ist die beste Methode frühestmöglich Kinder mit angeborenen Hörstörungen zu identifizieren. Es wird in der vorliegenden Arbeit das BERAphon® mit dem Echo-Screen TDA verglichen. Beide Geräte nutzen für das universelle Neugeborenen-Hörscreening die Hirnstammaudiometrie. Bei 5 von 226 Untersuchungsgängen war mit dem BERAphon® kein Screening möglich, bei 10 von 226 Untersuchungsgängen war mit dem Echo-Screen TDA kein Screening möglich. Der Unterschied ist bei einer Irrtumswahrscheinlichkeit von alpha < 0,05 statistisch nicht signifikant. Die Anzahl der auffälligen Untersuchungen zur Nachuntersuchung war mit 12 von 213 Untersuchungen bei beiden Geräten gleich. Die Gesamtscreeningdauer bei 85 gemessenen Untersuchungen lag als Median mit dem BERAphon® bei 2 Minuten 40 Sekunden, mit dem Echo-Screen TDA bei 6 Minuten 18 Sekunden. Bei 68 Untersuchungen lieferte das BERAphon® schneller ein Ergebnis als der Echo-Schreen TDA. Bei 17 Untersuchungen lieferte der Echo-Screen TDA schneller ein Ergebnis als das BERAphon®. Der Unterschied ist bei einer Irrtumswahrscheinlichkeit von alpha < 0,05 statistisch signifikant. Wesentliche Unterschiede gibt es in der Bedienungsfreundlichkeit der Geräte und beim Untersuchungskomfort für die Neugeborenen vor, während und nach dem Screening. / Universal newborn hearing screening is the best method for early identification of newborn children with kongenital hearing impaiment. This issue compares the BERAphon® to the Echo-Screen TDA, both using brainstem evoked response audiometry (BERA) for universal newborn hearing screening. In 5 out of 226 sreenings no result could be achieved with the BERAphon®, while in 10 out of 226 screenings no result could be achieved with the Echo-Screen TDA. The difference is not statistically significant (alpha < 0,05). The number of screenings to be looked after were 12 out of 213 in both devices. In 85 sreenings total screening time with the BERAphon® was 2 minutes 40 seconds and 6 minutes and 18 seconds with the Echo-Sreen TDA. In 68 out of 85 screenings the BERAphon® was first to deliver a result. In 17 out of 85 screenings the Echo-Screen TDA was first to deliver a result. This difference is statistically significant (alpha < 0,05). Substantially different were the easyness in using the devices und in comfort for the newborn child before, during and after the screening.

Two established methods, Electrochemical Impedance Spectroscopy (EIS) and extracellular recording, were implemented into a technology platform for non-invasive whole-cell biosensing. Electrical activity of cardiomyocytes and cell-substrate interaction of human ovarian cancer cells was monitored on electrode array chips. The performance of cells inside a microfluidic or closed low volume environment was investigated. Prior to the development of the entire microfluidic platform the two transducing methods were evaluated in single experiments. Processes as cellular attachment and detachment were monitored using EIS and single frequency impedance sensing. Electrodes of different size and structure were employed and compared for their impedance response. It was shown that small electrodes (A = 9·10-6 cm²) are more sensitive to cell-substrate interaction than larger ones (A = 9·10-5 cm²) and that the frequency used for analysis has a profound influence on the sensitivity. Data were modelled using a common equivalent circuit that represents a cell layer on an electrode resulting in an increase of the impedance magnitude by <170 % due to cell attachment. In order to demonstrate the potential of this method for biomedical applications, experiments related to anti-cancer strategies were performed. Cell detachment was induced by addition of synthetic integrin ligands and by hypericin mediated photodynamic therapy and monitored with impedance-based biosensing. Electrical activity of cardiomyocytes cultured on microelectrode arrays was monitored inside a microfluidic system. The chronotropic drug isoproterenol was applied using a robotic dispensing machine, and the resulting changes in spike rate and duration were compared with results gained by experiments with a large scale MEA chip. The experimental findings inspired the development of a technology platform that was finally evaluated by monitoring extracellular signals from myocytes in response to Isoproterenol. Another topic was the comparison of cell-substrate interaction monitored on various electrode structures.

Myelin is critical for the operation of a functional vertebrate nervous system, allowing for rapid saltatory conduction and providing trophic support to axons. In multiple sclerosis (MS), the immune system attacks myelin sheaths, leading to de-myelination of axons. De-myelinated axons not only lose their ability to conduct rapid nerve impulses, but are themselves susceptible to damage and loss. Long term demyelination leads to neuronal loss and the devastating symptoms of secondary stages of MS. One therapeutic approach which has been suggested is to improve the ability of oligodendrocyte precursor cells (OPCs) to differentiate into mature re-myelinating oligodendrocytes. This process is known to occur in vivo, however, the myelin produced appears reduced and the efficiency with which OPCs differentiate into myelinating oligodendrocytes (OLs) varies greatly. For example, the ability of OPCs from older mice to differentiate is reduced compared to those from young mice. This fact taken alongside the presence of many OPCs in some MS lesions which have failed to re-myelinate makes identifying compounds which can increase OPC differentiation into OLs a key goal for MS drug development. In this work, I use OPC to OL differentiation during zebrafish development as a model for differentiation of OLs more generally. Zebrafish are widely used for chemical screening, with recent developments in genetic manipulation, such as CRISPR/Cas9 gene editing and Tol2 transgenesis, allowing for production of targeted mutations and fluorescent reporter lines respectively. Retinoid X receptor-γ (RXRγ) has previously been identified as being transcriptionally upregulated during re-myelination. Moreover, treatment with 9-cis-retinoic acid, an agonist for the receptor, has been shown to improve remyelination in vivo in rats with toxin induced focal demyelination. I first present a manual chemical screen of a library of compounds designed to target RXRγ, from which I identify several compounds which reproducibly increase OLs in zebrafish. In order to assess whether any of the hit compounds could be acting as agonists for RXRγ, I have created a double knockout zebrafish lacking both genes coding for the zebrafish RXRγ homologues (rxrga and rxrgb). This line has been used to test the activity of hit compounds in a RXRγ loss of function background. Following this first chemical screen, it was clear that great improvements could be made to both throughput and robustness if the screen was automated. Using a commercially available fish handling robot which automates the imaging of plates of zebrafish embryos, known as the VAST BioImager, the throughput of our assay was increased from ~40 fish per day to up to around 300 to 400. We combined the VAST BioImager with a state of the art spinning disk confocal microscope, giving us (to the best of our knowledge) the world's fastest in vivo vertebrate screening system capable of orienting fish and imaging at sub-cellular resolution. This significant increase in rate of fish processing led to the need for an increase in the rate of image analysis. Much of the gains in throughput would be lost to time counting cells, and so I developed software to automate the image processing and analysis. The software developed is shown to closely match the abilities of a human to identify compounds which give significant increases in OLs, with very little human intervention required. In the final section of this work I present an example screen performed using the VAST BioImager in combination with the automated cell counting software, which I developed. The hits from this screen highlight our ability to automatically identify compounds that increase the number of OLs in the developing zebrafish. This method is broadly applicable to other central nervous system cell types and other methods of analysis can be integrated into the presented screening software.