An observational and theoretical study of the structure and propagation of the Madden-Julian Oscillation

Thesis (Ph.D.)--University of Washington, 2016-06

Lymphoproliferative disease of the ocular adnexa: A clinical and pathologic study with statistical analysis of 69 patients

Purpose: To evaluate the clinical features, treatment, and outcomes of a cohort of patients with ocular adnexal lymphoproliferative disease classified according to the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms and to perform a robust statistical analysis of these data. Methods: Sixty-nine cases of ocular adnexal lymphoproliferative disease, seen in a tertiary referral center from 1992 to 2003, were included in the study. Lesions were classified by using the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms classification. Outcome variables included disease-specific Survival, relapse-free survival, local control, and distant control. Results: Stage IV disease at presentation, aggressive lymphoma histology, the presence of prior or concurrent systemic lymphoma at presentation, and bilateral adnexal disease were significant predictors for reduced disease-specific survival, local control, and distant control. Multivariate analysis found that aggressive histology and bilateral adnexal disease had significantly reduced disease-specific Survival. Conclusions: The typical presentation of adnexal lymphoproliferative disease is with a painless mass, swelling, or proptosis; however, pain and inflammation occurred in 20% and 30% of patients, respectively. Stage at presentation, tumor histology, primary or secondary status, and whether the process was unilateral or bilateral were significant variables for disease outcome. In this study, distant spread of lymphoma was lower in patients who received greater than 20 Gy of orbital radiotherapy.

Excess in cardiovascular events on mondays: a meta-analysis analysis and prospective study

The aim of this paper was to summarise the reported excess in coronary events on Mondays, and examine the evidence for three competing explanations: stress, alcohol consumption, or registration errors. A review of the literature found 28 studies covering 16 countries and over 1.6 million coronary events. The overall Monday excess was small; in a population experiencing 100 coronary events per week there was one more event on Monday than other days. The excess was larger in men and in studies including sudden cardiac death or cardiac arrests. In a prospective study an increase in events on Mondays was associated with greater alcohol consumption, lower rainfall, and the month of January. The excess in coronary events on Mondays is a persistent phenomenon. The size of the effect varies widely between populations. There is some evidence of an association with alcohol consumption, but a definitive explanation remains elusive and is likely to remain so because of the smallness of the effect and the paucity of high quality data.

NMR studies of exchange between intra- and extracellular glutathione in human erythrocytes

Glutathione is the main source of intracellular antioxidant protection in the human erythrocyte and its redox status has frequently been used as a measure of oxidative stress. Extracellular glutathione has been shown to enhance intracellular reduced glutathione levels in some cell types. However, there are conflicting reports in the literature and it remains unclear as to whether erythrocytes can utilise extracellular glutathione to enhance the intracellular free glutathione pool. We have resolved this issue using a C-13-NMR approach. The novel use of L-gamma-glutamyl-L-cysteinyl-[2-C-13] glycine allowed the intra- and extracellular glutathione pools to be distinguished unequivocally, enabling the direct and non-invasive observation over time of the glutathione redox status in both compartments. The intracellular glutathione redox status was measured using H-1 spin-echo NMR, while C-13[H-1-decoupled] NMR experiments were used to measure the extracellular status. Extracellular glutathione was not oxidised in the incubations, and did not affect the intracellular glutathione redox status. Extracellular glutathione also did not affect erythrocyte glucose metabolism, as measured from the lactate-to-pyruvate ratio. The results reported here refute the previously attractive hypothesis that, in glucose-starved erythrocytes, extracellular GSH can increase intracellular GSH concentrations by releasing bound glutathione from mixed disulfides with membrane proteins.

A phase I biological and pharmacologic study of the heparanase inhibitor PI-88 in patients with advanced solid tumors

Purpose: PI-88 is a mixture of highly sulfated oligosaccharides that inhibits heparanase, an extracellular matrix endoglycosidase, and the binding of angiogenic growth factors to heparan sulfate. This agent showed potent inhibition of placental blood vessel angiogenesis as well as growth inhibition in multiple xenograft models, thus forming the basis for this study. Experimental Design: This study evaluated the toxicity and pharmacokinetics of PI-88 (80-315 mg) when administered s.c. daily for 4 consecutive days bimonthly (part 1) or weekly (part 2). Results: Forty-two patients [median age, 53 years (range, 19-78 years); median performance status, 1] with a range of advanced solid tumors received a total of 232 courses. The maximum tolerated dose was 250 mg/d. Dose-limiting toxicity consisted of thrombocytopenia and pulmonary embolism. Other toxicity was generally mild and included prolongation of the activated partial thromboplastin time and injection site echymosis. The pharmacokinetics were linear with dose. Intrapatient variability was low and interpatient variability was moderate. Both AUC and C-max correlated with the percent increase in activated partial thromboplastin time, showing that this pharmacodynamic end point can be used as a surrogate for drug exposure, No association between PI-88 administration and vascular endothelial growth factor or basic fibroblast growth factor levels was observed. One patient with melanoma had a partial response, which was maintained for >50 months, and 9 patients had stable disease for >= 6 months. Conclusion: The recommended dose of PI-88 administered for 4 consecutive days bimonthly or weekly is 250 mg/d. PI-88 was generally well tolerated. Evidence of efficacy in melanoma supports further evaluation of PI-88 in phase II trials.

Experimental and analytical study of the effect of contact angle on liquid convective heat transfer in microchannels

In this paper we examine the effect of contact angle (or surface wettability) on the convective heat transfer coefficient in microchannels. Slip flow, where the fluid velocity at the wall is non-zero, is most likely to occur in microchannels due to its dependence on shear rate or wall shear stress. We show analytically that for a constant pressure drop, the presence of slip increases the Nusselt number. In a microchannel heat exchanger we modified the surface wettability from a contact angle of 20 degrees-120 degrees using thin film coating technology. Apparent slip flow is implied from pressure and flow rate measurements with a departure from classical laminar friction coefficients above a critical shear rate of approximately 10,000 s(-1). The magnitude of this departure is dependant on the contact angle with higher contact angles surfaces exhibiting larger pressure drop decreases. Similarly, the non-dimensional heat flux is found to decrease relative to laminar non-slip theory, and this decrease is also a function of the contact angle. Depending on the contact angle and the wall shear rate, variations in the heat transfer rate exceeding 10% can be expected. Thus the contact angle is an important consideration in the design of micro, and even more so, nano heat exchangers. (c) 2006 Elsevier Ltd. All rights reserved.

A combined spectrophotometric and morphometric study of the lunar mare dome fields near Cauchy, Arago, Hortensius, and Milichius

In this Study we examine the spectral and morphometric properties of the four important lunar mare dome fields near Cauchy, Arago, Hortensius. and Milichius. We utilize Clementine UV vis mulfispectral data to examine the soil composition of the mare domes while employing telescopic CCD imagery to compute digital elevation maps in order to determine their morphometric properties, especially flank slope, height, and edifice Volume. After reviewing previous attempts to determine topographic data for lunar domes, we propose an image-based 3D reconstruction approach which is based on a combination of photoclinometry and shape from shading. Accordingly, we devise a classification scheme for lunar Marc domes which is based on a principal component analysis of the determined spectral and morphometric features. For the effusive mare domes of the examined fields we establish four Classes, two of which are further divided into two subclasses, respectively, where each class represents distinct combinations of spectral and morphometric dome properties. As a general trend, shallow and steep domes formed out of low-TiO2 basalts are observed in the Hortensius and Milichius dome fields, while the domes near Cauchy and Arago that consist of high-TiO2 basalts are all very shallow. The intrusive domes of our data set cover a wide continuous range of spectral and morphometric quantities, generally characterized by larger diameters and shallower flank slopes than effusive domes. A comparison to effusive and intrusive mare domes in other lunar regions, highland domes, and lunar cones has shown that the examined four mare dome fields display Such a richness in spectral properties and 3D dome shape that the established representation remains valid in a more global context. Furthermore, we estimate the physical parameters of dome formation for the examined domes based on a rheologic model. Each class of effusive domes defined in terms of spectral and morphometric properties is characterized by its specific range of values for lava viscosity, effusion rate, and duration of the effusion process. For our data set we report lava viscosities between about 10(2) and 10(8) Pas, effusion rates between 25 and 600 m(3) s(-1), and durations of the effusion process between three weeks and 18 years. Lava viscosity decreases with increasing R-415/R-750 spectral ratio and thus TiO2 content; however, the correlation is not strong, implying an important influence of further parameters like effusion temperature on lava viscosity.

XPS and bioactivity study of the bisphosphonate pamidronate adsorbed onto plasma sprayed hydroxyapatite coatings

This paper reports the use of X-ray photoelectron spectroscopy (XPS) to investigate bisphosphonate (BP) adsorption onto plasma sprayed hydroxyapatite (HA) coatings commonly used for orthopaedic implants. BPs exhibit high binding affinity for the calcium present in HA and hence can be adsorbed onto HA-coated implants to exploit their beneficial properties for improved bone growth at the implant interface. A rigorous XPS analysis of pamidronate, a commonly used nitrogenous BP, adsorbed onto plasma sprayed HA-coated cobalt-chromium substrates has been carried out, aimed at: (a) confirming the adsorption of this BP onto HA; (b) studying the BP diffusion profile in the HA coating by employing the technique of XPS depth profiling; (c) confirming the bioactivity of the adsorbed BR XPS spectra of plasma sprayed HA-coated discs exposed to a 10 mM aqueous BP solution (pamidronate) for periods of 1, 2 and 24 h showed nitrogen and phosphorous photoelectron signals corresponding to the BP confirming its adsorption onto the HA substrate. XPS depth profiling of the 2 h BP-exposed HA discs showed penetration of the BP into the HA matrix to depths of at least 260 nm. The bioactivity of the adsorbed BP was confirmed by the observed inhibition of osteoclast (bone resorbing) cell activity. In comparison to the HA sample, the HA sample with adsorbed BP exhibited a 25-fold decrease in primary osteoclast cells. (c) 2006 Elsevier B.V. All rights reserved.

Assessing the Conservation Status and Threats to Priority Plants: a threat assessment approach and case study in South-East Queensland, Australia

bstract: During the Regional Forest Agreement (RFA) process in south-east Queensland, the conservation status of, and threats to, priority vascular plant taxa in the region was assessed. Characteristics of biology, demography and distribution were used to assess the species' intrinsic risk of extinction. In contrast, the threats to the taxa (their extrinsic risk of extinction) were assessed using a decision-support protocol for setting conservation targets for taxa lacking population viability analyses and habitat modelling data. Disturbance processes known or suspected to be adversely affecting the taxa were evaluated for their intensity, extent and time-scale. Expert opinion was used to provide much of the data and to assess the recommended protection areas. Five categories of intrinsic risk of extinction were recognised for the 105 priority taxa: critically endangered (43 taxa); endangered (29); vulnerable (21); rare (10); and presumed extinct (2). Only 6 of the 103 extant taxa were found to be adequately reserved and the majority were considered inadequately protected to survive the current regimes of threatening processes affecting them. Data were insufficient to calculate a protection target for one extant taxon. Over half of the taxa require all populations to be conserved as well as active management to alleviate threatening processes. The most common threats to particular taxa were competition from weeds or native species, inappropriate fire regimes, agricultural clearing, forestry, grazing by native or feral species, drought, urban development, illegal collection of plants, and altered hydrology. Apart from drought and competition from native species, these disturbances are largely influenced or initiated by human actions. Therefore, as well as increased protection of most of the taxa, active management interventions are necessary to reduce the effects of threatening processes and to enable the persistence of the taxa.