Proton pump inhibitors and the risk of fractures in older adults: a population-based retrospective cohort study

Thesis (Master's)--University of Washington, 2016-06

The impact of computer display height and desk design on 3D posture during information technology work by young adults

Computer display height and desk design to allow forearm support are two critical design features of workstations for information technology tasks. However there is currently no 3D description of head and neck posture with different computer display heights and no direct comparison to paper based information technology tasks. There is also inconsistent evidence on the effect of forearm support on posture and no evidence on whether these features interact. This study compared the 3D head, neck and upper limb postures of 18 male and 18 female young adults whilst working with different display and desk design conditions. There was no substantial interaction between display height and desk design. Lower display heights increased head and neck flexion with more spinal asymmetry when working with paper. The curved desk, designed to provide forearm support, increased scapula elevation/protraction and shoulder flexion/abduction.

Treatment of ocular allergies:nonpharmacologic, pharmacologic and immunotherapy

Ocular allergy is a significant and growing issue worldwide but for many patients, it is often not differentiated from systemic conditions, such as hay fever. Management of seasonal and perennial allergic conjunctivitis is often poor. Management is principally through avoidance measures (blocking or hygiene), nonpharmaceutical (such as artificial tears and cold compresses) and pharmaceutical (such as topical antihistamines and prophylactic mast cell stabilizers). Vernal and atopic keratoconjunctivitis are more severe and generally need treatment with NSAIDs, steroids and immunomodulators. Giant papillary conjunctivitis can be related to allergy but also is often contact lens related and in such cases can be managed by a period of abstinence and replacement of the lens or a change in lens material and/or design. Immunotherapy can be efficacious in severe, persistent cases of contact lens or allergic conjunctivitis.

Grewia polysaccharide gum as a pharmaceutical excipient

Grewia gum is obtained from the inner stem bark of the edible plant Grewia mollis Juss (Fam. Tiliaceae) which grows widely in the middle belt region of Nigeria, and is also cultivated. The dried and pulverised inner stem bark is used as a thickening agent in some food delicacies in that region of the country. This ability of the material to increase solution viscosity has generated a lot of interest and is the catalysing momentum for this research. Such materials have been used as stabilizers or suspending agents in cosmetics, foods and liquid medications, and as mucoadhesives and controlled release polymeric matrices in solid dosage forms. The physicochemical characterization of candidate excipients forms an essential step towards establishing suitability for pharmaceutical application. For natural gums, this usually requires isolation of the gum from the storage site by extraction processes. Grewia polysaccharide gum was extracted and dried using techniques such as air-drying, freeze-drying or spray-drying. Component analysis of the gum showed that it contains five neutral sugars: glucose, galactose, rhamnose, arabinose and xylose. The gum contains traces of elements such as zinc, magnesium, calcium and phosphorus. At low substance weight, the gum hydrates in aqueous medium swelling and dispersing to give a highly viscous dispersion with pseudoplasmic flow behaviour. The method by which drying is achieved can have significant effect on some physicochemical properties of the gum. Consequently, the intrinsic viscosity and molecular weight, and parameters of powder flow were shown to differ with the method of drying. The gum has good thermal stability. In comparison with established excipients, grewia gum may be preferable to gum Arabic or sodium carboxymethylcellulose as a suspending agent in ibuprofen suspension formulations. The release retardant property of the gum was superior to guar and Metolose® in ibuprofen matrices. Similarly, carboxy methylcellulose, Methocel®, gum Arabic or Metolose® may not be preferable to grewia gum when controlled release of a soluble drug like cimetidine is indicated. The mucoadhesive performance of the gum compared favourably with excellent mucoadhesives such as hydroxypropyl methylcellulose, carboxymethylcellulose, guar and carbopol 971 P.

The behaviour of antioxidants in polyolefins under conditions of U.V. exposure

The effects of antioxidants and stabilizers on the oxidative degradation of polyolefins (low density polyethylene [LDPE] and polypropylene [PPJ have been studied after subjecting to prior high temperature processing treatments. The changes in the both chemical and physical properties of unstabilized polymers occurring during processing were found to be strongly dependent on the amount of oxygen present in the mixer. Subsequent thermal and photo-oxidation showed very similar characteristics and the chromophore primarily responsible for:both thermo and photooxidative degradation of unstabilized polymers was found to be hydroperoxide formed during processing. Removal of hydroperoxide by heat treatment in an inert atmosphere although increasing ketonic carbonyl concentration, markedly decreased the rate of photo-oxidation, introducing an induction period similar to that of an unprocessed sample. It was concluded that hydroperoxides are the most important initiators in normally processed polymers during the early stages of photo-oxidation. Antioxidants such as metal dithiocarbamates which act by destroying peroxides into non-radica1 products were found to be efficient melt stabilizers for polyolefins and effective UV stabilizers during the initial photo-oxidation stage, whilst a phenolic antioxidant, n-octadecyl-3-(3',5'-di-terbutyl 4'hydroxypheny1) propionate (Irganox 1076) retarded photo-oxidation rate in the later stages. A typical 'UV absorber' 2-hydroxy-4-octyloxy-benzophenone (HOBP) has a minor thermal antioxidant action but retarded photo-oxidation at all stages. A substituated piperidine derivative, Bis [2.2.6.6-tetramethylpiperidlnyl-4] sebacate (Tinuvin 770) behaved as an pro-oxidant during thermal oxidation of polyolefins but was an effective stabilizer against UV light. The UV absorber, HOBP synergised effectively with both peroxide decomposing antioxidants (metal dithiocarbamates) and a chain-breaking antioxidant (Irganox 1076) during photo-oxidation of the poymers studed whereas the combined effect was additive during thermal oxidation. By contrast, the peroxide decornposers and chain-breaking antioxidant (Irganox 1076) which were effective synergists during thermal oxidation of LDPE· were antagonistic during photo-oxidation. The mechanisms of these processes are discussed.

Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Context - Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. Objective - To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design - Cross-sectional, case-control, whole-brain DTI using TBSS. Setting - University research institute. Participants - Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures - Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results - Subjects with BD vs controls had significantly greater FA (t > 3.0, P = .05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P = .05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P < .01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P < .01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions - To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

The use of topiramate in mood stabilization

OBJECTIVE: To review data on the effectiveness of topiramate as a mood stabilizer. DATA SOURCES: Clinical literature accessed through MEDLINE (1985-September 2001) and the manufacturer. Key search terms included topiramate, mania, mood stabilizer, and bipolar disorder. DATA SYNTHESIS: The traditional standard therapy for bipolar disorder has been lithium. Other mood stabilizers are increasingly being used to manage this complex disorder. Studies that used topiramate in bipolar disorders were evaluated. CONCLUSIONS: The present data from open trials suggest that topiramate may possibly possess antimanic properties. Controlled, double-blind studies are required to confirm this efficacy

Gabapentin treatment for bipolar disorders

OBJECTIVE: To review the effectiveness data on the use of gabapentin in bipolar disorders. DATA SOURCES: Clinical literature was accessed through MEDLINE (January 1985–November 2000). Key search terms included gabapentin, mood stabilizer, and bipolar disorder. DATA SYNTHESIS: Bipolar disorder is a complex condition that can be difficult to treat effectively. Mood stabilizers are increasingly being used to manage bipolar disorder. Studies that used gabapentin in bipolar disorders are evaluated. CONCLUSIONS: From the data presented, gabapentin cannot be recommended for treatment of bipolar disorder. Further studies are required to determine whether gabapentin has any role in the management of bipolar disorder.

Padronização de testes para avaliação do estado de mania e potencial anti-maníaco de um agonista do receptor NOP

Bipolar disorder is characterized by mood impairment, alternating between mania/hypomania and depression, and its exact pathophysiology is already unknown. The treatment of bipolar disorder is based on prevention of the manic and depressive episodes using mood stabilizers. Nociceptin/orfanin FQ (N/OFQ) is an endogenous heptadecapeptide which binds as an agonist to NOP receptor, which is a G-coupled inhibitory receptor. N/OFQ and its receptor modulate a lot of functions in the organism, including emotional processes. It is known that the plasmatic concentration of N/OFQ is altered in patients in both phases depressive and manic of bipolar disorder and it is assumed that this system has a role on the etiology of this disorder. Concerning mania, the animal models used in research tend to focus in an unique aspect of the manic behavior, as hyperactivity or agressivity. In the 60’s, the hole board test was proposed, and it consists of an apparatus with holes where a behavior known as head-dippings is measured. High levels of head-dippings are suggestive of neophilia, while low levels can be characteristic of an anxious-like behavior. As the increase of exploratory and goal-directed behavior are characteristics of manic behavior, this test could help in mania research. Thus, this work was organized in 3 steps and aims to: (1) investigate the induction of a manic-like state promoted by ouabain, a Na+/K+-ATPase inhibitor, in the mouse open field test; (2) set up the hole board as a test to measure manic-like behaviors; and (3) investigate the N/OFQ effects in prevention of this kind of behavior on hole board. Male Swiss mice were used in this study, and they take part of only one of the described steps. Depending on the step performed, mice received one or more of the following treatments: (1) ouabain 10-6 , 10-5 , 10-4 , 10-3 or 10-2 M, intracerebroventricular (icv); (2) sodium valproate 300 mg/kg, intraperitoneal (ip); (3) sodium valproate 400 mg/kg, ip; (4) diazepam 1 mg/kg, ip; (5) methylphenidate 10 mg/kg, ip; and (6) N/OFQ 0,1 or 1 nmol, icv. The results suggest that hole board can be used to evaluate a manic state, through analysis of different animal behaviors. However, it was not possible to standard the model of Na+ /K+ -ATPase dysfunction through ouabain administration in mice. Moreover, the data suggest that N/OFQ, at the doses tested, has not affected the methylphenidate-induced mania-like behavior. Taken together, the results point to a new approach of manic research, through the hole board using. However, more studies are necessary in order to verify the role of N/OFQ system on bipolar disorder.

Design rationnel de nanothermomètres programmables à base d’ADN

Développer de nouveaux nanomatériaux, interrupteurs et machines nanométriques sensibles à de petites variations de température spécifiques devrait être de grande utilité pour une multitude de domaines œuvrant dans la nanotechnologie. De plus, l’objectif est de convaincre le lecteur que les nanotechnologies à base d’ADN offrent d’énormes possibilités pour la surveillance de température en temps réel à l’échelle nanométrique. Dans la section Résultats, nous exploitons les propriétés de l’ADN pour créer des thermomètres versatiles, robustes et faciles à employer. En utilisant une série de nouvelles stratégies inspirées par la nature, nous sommes en mesure de créer des nanothermomètres d’ADN capables de mesurer des températures de 25 à 95°C avec une précision de <0.1°C. En créant de nouveaux complexes d’ADN multimériques, nous arrivons à développer des thermomètres ultrasensibles pouvant augmenter leur fluorescence 20 fois sur un intervalle de 7°C. En combinant plusieurs brins d’ADN avec des plages dynamiques différentes, nous pouvons former des thermomètres montrant une transition de phase linéaire sur 50°C. Finalement, la vitesse de réponse et la précision des thermomètres développés et leur réversibilité sont illustrées à l’aide d’une expérience de surveillance de température à l’intérieur d’un unique puits d’un appareil de qPCR. En conclusion, les applications potentielles de tels nanothermomètres en biologie synthétique, imagerie thermique cellulaire, nanomachines d’ADN et livraison contrôlée seront considérées.

Design rationnel de nanothermomètres programmables à base d’ADN

Développer de nouveaux nanomatériaux, interrupteurs et machines nanométriques sensibles à de petites variations de température spécifiques devrait être de grande utilité pour une multitude de domaines œuvrant dans la nanotechnologie. De plus, l’objectif est de convaincre le lecteur que les nanotechnologies à base d’ADN offrent d’énormes possibilités pour la surveillance de température en temps réel à l’échelle nanométrique. Dans la section Résultats, nous exploitons les propriétés de l’ADN pour créer des thermomètres versatiles, robustes et faciles à employer. En utilisant une série de nouvelles stratégies inspirées par la nature, nous sommes en mesure de créer des nanothermomètres d’ADN capables de mesurer des températures de 25 à 95°C avec une précision de <0.1°C. En créant de nouveaux complexes d’ADN multimériques, nous arrivons à développer des thermomètres ultrasensibles pouvant augmenter leur fluorescence 20 fois sur un intervalle de 7°C. En combinant plusieurs brins d’ADN avec des plages dynamiques différentes, nous pouvons former des thermomètres montrant une transition de phase linéaire sur 50°C. Finalement, la vitesse de réponse et la précision des thermomètres développés et leur réversibilité sont illustrées à l’aide d’une expérience de surveillance de température à l’intérieur d’un unique puits d’un appareil de qPCR. En conclusion, les applications potentielles de tels nanothermomètres en biologie synthétique, imagerie thermique cellulaire, nanomachines d’ADN et livraison contrôlée seront considérées.

Rowing Biomechanics: Technique Changes with an Increase of Power Demand

The sport of rowing has become more popular in the past decade. While it is a relatively low impact sport, injuries can occur, specifically to the ribs (Karlson K. A., 1998) and more often in female athletes (Hickey, Fricker, & McDonald , 1997). It has been proposed that as the athlete rows, applying a cyclical load to the body, the mid trapezius fatigues and is unable to resist the force produced during the drive phase (Warden S. J., Gutschlag, Wajswelner, & Crossley, 2002). Once this happens, the scapulae are then pulled anterio-laterally which increases the compression force on the ribs, increasing the risk of injury. The rowing motion of 12 female varsity and club rowers was tracked as they completed a fatiguing rowing test on a rowing ergometer. Results showed that the curvature of thoracic spine changed throughout the rowing cycle but did not change with increasing power level. The transverse shoulder angle decreased (the upper back was less straight) as power level increased (R2=-0.69±19), suggesting that the scapula moved anterio-laterally. This may be that as it tired, the mid-trapezius was unable to hold the scapulae in position. The decreasing transverse shoulder angle when the power level is increased indirectly supports the fatiguing of the retractor muscles as a mechanism of injury. It would be valuable to understand the limitations of each athlete and to be able to prescribe the optimal training zone to reduce the risk of injury.

THE MICROSTRUCTURES OF ZR-EXCEL ALLOY: EFFECTS OF HEAVY ION IRRADIATION, PLASTIC DEFORMATION, THERMAL TREATMENT AND IN-SITU HEATING

Zr-Excel alloy (Zr-3.5Sn-0.8Nb-0.8Mo) is a dual phase (α + β) alloy in the as-received pressure tube condition. It has been proposed to be the pressure tube candidate material for the Generation-IV CANDU-Supercritical Water Reactor (CANDU-SCWR). In this dissertation, the effects of heavy ion irradiation, deformation and heat treatment on the microstructures of the alloy were investigated to enable us to have a better understanding of the potential in-reactor performance of this alloy. In-situ heavy ion (1 MeV) irradiation was performed to study the nucleation and evolution of dislocation loops in both α- and β-Zr. Small and dense type dislocation loops form under irradiation between 80 and 450 °C. The number density tends to saturate at ~ 0.1 dpa. Compared with the α-Zr, the defect yield is much lower in β-Zr. The stabilities of the metastable phases (β-Zr and ω-Zr) and the thermal-dynamically equilibrium phase, fcc Zr(Mo, Nb)2, under irradiation were also studied at different temperatures. Chemi-STEM elemental mapping was carried out to study the elemental redistribution caused by irradiation. The stability of these phases and the elemental redistribution are strongly dependent on irradiation temperature. In-situ time-of-flight neutron diffraction tensile and compressive tests were carried out at different temperatures to monitor lattice strain evolutions of individual grain families during these tests. The β-Zr is the strengthening phase in this alloy in the as-received plate material. Load is transferred to the β-Zr after yielding of the α-Zr grains. The temperature dependence of static strain aging and the yielding sequence of the individual grain families were discussed. Strong tensile/compressive asymmetry was observed in the {0002} grain family at room temperature. The microstructures of the sample deformed at 400 °C and the samples only subjected to heat treatment at the same temperature were characterized with TEM. Concentration of β phase stabilizers in the β grain and the morphology of β grain have significant effect on the stability of β- and ω-Zr under thermal treatment. Applied stress/strain enhances the decomposition of isothermal ω phase but suppresses α precipitation inside the β grains at high temperature. An α → ω/ZrO phase transformation was observed in the thin foils of Zr-Excel alloy and pure Zr during in-situ heating at 700 °C in TEM.

Roadside erosion research in selected Iowa counties, 1972

This research project discusses roadside stabilization along secondary roads. Another objective was to investigate various commercial soil stabilizers, as a replacement for straw mulch, to control soil erosion before vegetation.

Budowa, asymetria i dymorfizm płciowy stawu ramiennego w populacji średniowiecznej i współczesnej

Wydział Biologii: Instytut Antropologii