A novel fluorophotometer for measuring concentration and diffusion of autofluorescent ophthalmic medication in the human eye

As society is aging, the frequency of age-related diseases is increasing. An area of age-related diseases that requires special attention is that of ocular diseases as they eventually cause blindness and therefore have a huge impact on the quality of life of the patient. Understanding the underlying cause of the disease and being able to treat it effectively is thus becoming increasingly important. To evaluate the effectiveness of a treatment, the behaviour of the medication in the body needs to be known or estimated. Monitoring the diffusion of medication is commonly referred to as pharmacokinetics, and the pharmacokinetics of ophthalmic medication are currently assessed by sacrificing animal eyes at given points in time after the application of the drug. This procedure does not allow for a high enough temporal resolution and incorporates a number of disadvantages such as the fact that the eyes are non-human and that the behaviour of the drug has to be extrapolated from the data obtained from different eyes. An instrument that can measure the pharmacokinetics of ophthalmic medication in a non-invasive manner will therefore increase the knowledge about the behaviour of the compound of interest considerably. This thesis presents a novel ocular fluorophotometer which can measure the diffusion of inherently ophthalmic drugs with high temporal and axial resolution (0.6 s and 124 μm, respectively) and a sensitivity of 2 nM in terms of Fluorescein concentration. The design process of the instrument and its performance in terms of resolution and noise are discussed. Thorough consideration of the eye safety of the instrument is presented. The instrument is calibrated for both a fluorescence standard (Fluorescein sodium salt) and an ophthalmic drug for treating open angle glaucoma (Brimonidine) and it is shown that the concentration of a sample with high signal to noise ratio can be accurately recovered with an error below 20%. It is however found that for samples with less good signal to noise ratios the accuracy decreases significantly. The repeatability of the measurements is also assessed and found to be slightly worse than the accuracy with an error of below 23% within one week. The calibration in in vitro porcine eyes is also discussed and suggestions made for its improvement. Further measurements of diffusing fluorescent compounds are then presented and discussed. It is found that the diffusion can be monitored with high temporal resolution and that the concentration after complete diffusion is measured correctly. Finally, measurements of in vivo eyes of human volunteers are presented and discussed. The instrument is shown to be of a similar standard to a commercially available instrument, and it is believed that the instrument presented here has the potential to become the new gold standard ocular fluorophotometer

Nonlinear dynamics of mode-locking optical fiber ring lasers

We consider a model of a mode-locked fiber ring laser for which the evolution of a propagating pulse in a birefringent optical fiber is periodically perturbed by rotation of the polarization state owing to the presence of a passive polarizer. The stable modes of operation of this laser that correspond to pulse trains with uniform amplitudes are fully classified. Four parameters, i.e., polarization, phase, amplitude, and chirp, are essential for an understanding of the resultant pulse-train uniformity. A reduced set of four coupled nonlinear differential equations that describe the leading-order pulse dynamics is found by use of the variational nature of the governing equations. Pulse-train uniformity is achieved in three parameter regimes in which the amplitude and the chirp decouple from the polarization and the phase. Alignment of the polarizer either near the slow or the fast axis of the fiber is sufficient to establish this stable mode locking

Beluga, Delphinapterus leucas, Distribution and Survey Effort in the Gulf of Alaska

Beluga, Delphinapterus leucas, distribution in the Gulf of Alaska and adjacent inside waters was examined through a review of surveys conducted as far back as 1936. Although beluga sightings have occurred on almost every marine mammal survey in northern Cook Inlet (over 20 surveys reported here), beluga sightings have been rare outside the inlet in the Gulf of Alaska. More than 150,000 km of dedicated survey effort in the Gulf of Alaska resulted in sightings of over 23,000 individual cetaceans, of which only 4 beluga sightings (5 individuals) occurred. In addition, nearly 100,000 individual cetaceans were reported in the Platforms of Opportunity database; yet, of these, only 5 sightings (39 individuals) were belugas. Furthermore, approximately 19 beluga sightings (>260 individuals), possibly including resightings, have been reported without information on effort or other cetacean sightings. Of the 28 sightings of belugas outside of Cook Inlet, 9 were near Kodiak Island, 10 were in or near Prince William Sound, 8 were in Yakutat Bay, and 1 anomalous sighting was well south of the Gulf. These sightings support archaeological and commercial harvest evidence indicating the only persistent group of belugas in the Gulf of Alaska occurs in Cook Inlet

Strategic Planning: Plan-to-plan documentation

As part of the strategic planning process begun in 2020, the Grand Valley State University Libraries Strategic Planning Team developed a collection of planning-to-plan documentation to support the development of a new strategic planning framework. This documentation includes descriptions of the project and scope, the strategic planning team and their roles, and the timeline for the planning process. It also outlines the design principles that will guide the planning process and the ways that the team will incorporate methodologies like SOAR, North Star, and Design Thinking

Construction of an in vitro bistable circuit from synthetic transcriptional switches

Information processing using biochemical circuits is essential for survival and reproduction of natural organisms. As stripped-down analogs of genetic regulatory networks in cells, we engineered artificial transcriptional networks consisting of synthetic DNA switches, regulated by RNA signals acting as transcription repressors, and two enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H. The synthetic switch design is modular with programmable connectivity and allows dynamic control of RNA signals through enzyme-mediated production and degradation. The switches support sharp and adjustable thresholds using a competitive hybridization mechanism, allowing arbitrary analog or digital circuits to be created in principle. As an example, we constructed an in vitro bistable memory by wiring together two synthetic switches and performed a systematic quantitative characterization. Good agreement between experimental data and a simple mathematical model was obtained for switch input/output functions, phase plane trajectories, and the bifurcation diagram for bistability. Construction of larger synthetic circuits provides a unique opportunity for evaluating model inference, prediction, and design of complex biochemical systems and could be used to control nanoscale devices and artificial cells

Met and unmet need for mental health care before and during the COVID-19 pandemic

There is a concern that the coronavirus disease 2019 (COVID-19) pandemic will generate large unmet needs for mental health care. Using data from an epidemiological psychiatric diagnostic interview survey (n = 2159) conducted on a probability sample from the general population, the proportions of met and unmet need for mental health care among individuals with and without mental disorders were compared before and during the COVID-19 pandemic. The results showed no statistical difference in met and unmet need for mental health care, but point estimates were suggestive of a higher unmet need for care among those with a current mental disorder after the lock-down period.publishedVersio

Visual and behavioral profiles of socially \u27at-risk\u27 juveniles

The aim of this investigation is to examine the prevalence of visual dysfunction, behavior problems, and co-existing conditions between the two in the socially at-risk juvenile population. A sample of 70 socially at risk juveniles was drawn from alternative classrooms in the public schools and a training facility for boys. A visual screening battery was administered on -site at each of the three facilities. The screening consisted of: acuity measurement, static retinoscopy, cover test, near point of convergence, stereo acuity, accommodative facility, mobility (DEM), visual-motor perception (Beery), and direct ophthalmoscopy. Behavior profiles were assessed by the classroom teacher utilizing the Child Behavior Check List (Achenbach). Failure was designated as any clinical score. All 70 subjects failed some area of visual function ranging from 0% in ocular disease to 70% in visual-motor perception to 7 1 % in refractive problems. All. subjects displayed some sort of clinically significant behavior problem ranging from 4% in somatic complaints to 27% who measured anxious/depressed. Co-existing conditions with \u27fail scores that were 20% congruent for boys were: refractive status: withdrawn/depressed; visual motor perception: anxious/depressed. Co-existing conditions with \u27fail\u27 scores that were 20% congruent for girls were: refractive status: delinquent behavior; accommodative facility: thought problems, attention problems, delinquent behavior; Visual motor perception: delinquent behavior. It was found that juveniles from alternative classrooms exhibit a high prevalence of visual dysfunction along with certain behavior problems. This study suggests that certain visual dysfunction might be viewed as relative risk factors in these behavior problems. No conclusion can be drawn as to cause and effect. However, one is tempted to speculate that juveniles with visual dysfunction will do less well meeting academic demands and hence become prime targets for alternative education