Background: Cervical cancer is a leading cause of death in Tanzanian women, with annual age-standardized mortality of 38 per 100,000. While organized screening programs have minimized cervical cancer rates in the developed world, a national prevention program has not yet been instituted in Tanzania. Though screening is available at clinics in the Kilimanjaro region, uptake of these services is reported to be low. The objectives of this thesis were: 1) to describe the knowledge, attitudes and practices of cervical cancer screening in rural and urban Kilimanjaro women, 2) to determine the main barriers preventing women from being screened, and 3) to identify important determinants of screening status and screening acceptability in the population. Methods: A cross-sectional survey was administered to 312 rural and 280 urban women in the region over June-July 2012. The sample was obtained through a multistage random sampling strategy. Descriptive statistics were performed to address Objectives 1 and 2, while multivariate logistic regression models were created using generalized estimating equations to address Objective 3. Results: Awareness of cervical cancer in the sample was high, but women had less knowledge of screening tests for the disease. The proportion of ever-screened women was significantly lower in the rural (4%) than in the urban (8%) sample. The most common barrier in never-screened women was not knowing that screening existed, followed by anticipated cost of the procedure. Travel distance was a more frequent concern in rural women. Older age, being married, cervical cancer knowledge and healthcare access factors were significantly associated with screening status in urban women, while only older age and condom use were associated in rural women. Personal beliefs about risk were associated with screening acceptability in never-screened women. Willingness to be screened was low in urban women with high socioeconomic status. Conclusions: Participation in cervical screening is extremely low in the Kilimanjaro region due to both access-related and personal barriers. While Tanzania awaits a national screening program, the identified determinants may inform regional screening and education initiatives aimed at increasing screening coverage in the Kilimanjaro area. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2013-09-30 14:24:36.139

STOP-Bang is a tool for predicting the likelihood for sleep-disordered breathing (SDB). In the conventional score, all variables are dichotomous. Our aim was to identify whether modifying the STOP-Bang scoring tool by weighting the variables could improve test characteristics.

ABSTRACT SCREENING PROSTATE SPECIFIC ANTIGEN EFFECTS ON RACIAL DISPARATE MORTALITY: A PROPENSITY SCORE ANALYSIS By R. David McNally, Ph.D., M.S.H.A. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2011 Dissertation Chair: Jeffrey S. Legg, Ph.D., Associate Professor and Chair, Doctoral Program in Health Related Sciences Department of Radiation Sciences Prostate cancer is the most commonly diagnosed cancer among men in the United States. It is frequently cited that racial disparities in mortality between Caucasian and African American men with localized prostate cancer exist. In addition, the question of whether prostate cancer screening with the prostate specific antigen blood test (PSA) leads to reduced mortality remains unanswered. Outcomes theory and survival analysis have shown controversial inconsistencies in support of early detection methods for prostate cancer to the extent that experts in the medical community do not agree on best-practice guidelines suggestive of eliminating such disparities and reducing mortality. The purpose of this study was to explore the relationship between screening PSA tests and racial differences in mortality among Caucasian and African American men with application of a propensity scoring analysis on a large population-based data set. Prostate cancer patients diagnosed from January 1, 1986 through December 31, 2006 (n = 515,802 cases) from the SEER-17 data set linked to Medicare claims files were included. A separate analysis using a 5% randomized group of over 263,000 men without prostate cancer was also examined. The results demonstrated that no statistically significant differences in mortality between Caucasians and African Americans in the prostate cancer group existed (p=0.993). Further, the same result was found among men from the 5% randomized group without prostate cancer (p= 0.832), that no statistically significant difference exists for this study population when using a propensity scoring analysis and a conditional Cox regression model. From both analyses, no survival benefit was found for screened men versus non-screened men when using the PSA test for early detection. In addition, because age is a well-known predictor of death, a separate analysis was performed on age-matched men. The results for the age analysis also demonstrated no statistically significant differences in racial mortality or whether screening PSA reduced mortality after applying a propensity scoring analysis to a conditional Cox regression model. In conclusion, it is believed that using a propensity scoring method and Cox regression analysis improved the evaluation of this large population data set where censoring for survival time was important and where matched pairs were utilized. Further work in health services research using large population-based data sets should be pursued and incorporating Cox regression with a propensity analysis can be helpful.

PhD - Science / Screening of asymptomatic women using X-ray mammography technique is very common in many parts of the world in view of the prevalence of breast cancer among women. Mammography X-ray procedures are well established; with radiation dose measurements usually carried out using air ionisation chamber despite its inherent disadvantages. In this study, the various parameters necessary for accurate dose calculations from mammography X-ray energies and their effect on the calculated dose values, the relationship between dose, breast size, image quality and X-ray tube parameters as well as an alternative method for dose measurements, were systematically investigated. A method is presented for calculating accurately the mass attenuation and mass-energy coefficients for any energy bin of interest in the photon energy region 1-20 keV from existing mass attenuation and mass-energy coefficients data. Data fitting procedure was used for the study using an established equation. The results of the study showed that when data points containing high and low energies such as 1 - 200 keV are fit together with a single set of parameters, an overestimation of about 20% at the lower energies with far greater deviations at higher energies can result. It has been shown that grouping data into smaller energy regions when fitting would lead to accurate calculations of the mass attenuation or mass energy-absorption data. This is especially important if the data were to be used in low energy photon calculations such as would be the case for mammography beams. An investigation into the effect of pressure, temperature and humidity in air on photon fluence at a typical mammography, low bremsstrahlung energy (25 kVp), has been carried out. The results of the investigation showed that air kerma values from an X-ray spectrum that has significant lower energy components is likely to be more sensitive to changes in pressure, temperature and humidity than the air kerma from an X-ray spectrum with lower energy components less pronounced. Mean glandular dose (MGD) values had been calculated for various tube potentials and tube loadings (TL) using direct measurements of the incident entrance air kerma (ESAK) at the surface of a standard breast phantom and also from spectral measurements acquired with a solid-state detector. Detailed presentations of dose measurements from direct measurements and also from X-ray spectral data employing the established methods are given. Comparisons of the MGD values thus derived are presented and the relationship between MGD, phantom thickness, image quality and tube operating parameters is discussed. The possibility of evaluating radiation dose from mammography X-ray beams using constructed probes with diamond as the active radiation sensing material has been studied. Diamond has been used in the conduction mode whereby electrodes are connected to it and the resulting current from the interaction of the ionizing radiation with the diamond detected. Single crystal diamonds produced under high pressure and temperature (HPHT), as well as polycrystalline diamonds manufactured by the chemical vapour deposition (CVD) method were used. Suitable diamond stones were carefully selected for the study using various techniques. The probe was constructed entirely using tissue equivalent materials. In current practice diamond in the form of thin plates are used in the “flat-on” geometry, where the radiation beam to be monitored or measured, impinges on the flat face of the diamond. In this work it was found that using diamond plates in a side-on, or “edgeon”, geometry improves the collection efficiency of the diamond. The probe has been designed for radiation detection in both “edge-on” and “flat-on” sensor geometry profiles without having firstly to unseat the diamond sensor element from its original position within the probe housing before taking measurements. The study has shown that with the “edge-on” geometry configuration, radiation from impinging photons with energies below 30 keV can be made to deposit almost all (about 90%) of their energy into the sensor. The probe was designed for use in combination with commercially available electrometer systems. The response of the diamond probe to changes in radiation dose correlated well with that obtained from a secondary standard ionization chamber at the same X-ray tube settings.

This thesis describes the development and refinement of a number of techniques for molecular docking and ligand database screening, as well as the application of these techniques to predict the structures of several protein-ligand complexes and to discover novel ligands of an important receptor protein. Global energy optimisation by Monte-Carlo minimisation in internal co-ordinates was used to predict bound conformations of eight protein-ligand complexes. Experimental X-ray crystallography structures became available after the predictions were made. Comparison with the X-ray structures showed that the docking procedure placed 30 to 70% of the ligand molecule correctly within 1.5A from the native structure. The discrimination potential for identification of high-affinity ligands was derived and optimised using a large set of available protein-ligand complex structures. A fast boundary-element solvation electrostatic calculation algorithm was implemented to evaluate the solvation component of the discrimination potential. An accelerated docking procedure utilising pre-calculated grid potentials was developed and tested. For 23 receptors and 63 ligands extracted from X-ray structures, the docking and discrimination protocol was capable of correct identification of the majority of native receptor-ligand couples. 51 complexes with known structures were predicted. 35 predictions were within 3A from the native structure, giving correct overall positioning of the ligand, and 26 were within 2A, reproducing a detailed picture of the receptor-ligand interaction. Docking and ligand discrimination potential evaluation was applied to screen the database of more than 150000 commercially available compounds for binding to the fibroblast growth factor receptor tyrosine kinase, the protein implicated in several pathological cell growth aberrations. As expected, a number of compounds selected by the screening protocol turned out to be known inhibitors of the tyrosine kinases. 49 putative novel ligands identified by the screening protocol were experimentally tested and five compounds have shown inhibition of phosphorylation activity of the kinase. These compounds can be used as leads for further drug development.

Globally, it is estimated that 240 million people are infected with chronic viral hepatitis B and in excess of 185 million people with chronic hepatitis C. The burden of disease from hepatitis is concentrated in developing countries where transmission of HBV occurs predominantly from mother to child (vertical transmission) and transmission of HCV through unsafe medical procedures and the transfusion of unscreened blood products. Global patterns of migration favour the movement of individuals from countries with medium or high risk prevalence of chronic viral hepatitis to countries with traditionally low prevalence among their indigenous populations, including the United Kingdom (UK). In excess of 3.2% of the global population are international migrants, posing important implications for healthcare systems in host nations. It is predicted that up to 7 million first and second generation immigrants, originating from high prevalence countries for viral hepatitis now reside permanently in the UK. However, as a result of deficiencies in screening initiatives, the prevalence and associated burden of these diseases in these high-risk populations residing in the UK is yet to be determined. In order to establish the feasibility of inviting first and second generation immigrant populations to participate in viral hepatitis testing in primary care, as well to determine the prevalence and demography of viral hepatitis in four areas of the UK, a randomised controlled cross sectional cluster trial was conducted. In HepFree clinical computer systems in general practice surgeries were interrogated to identify the target population that was then approached using a variety of different invitations to determine the most appropriate method for engaging this population. The outcomes of viral hepatitis testing from practices in one area of the UK are described in this thesis. Despite multiple challenges encountered both in engaging practices and individuals in trial participation, results of this investigation suggest that if it is found to be cost effective, then viral hepatitis screening is feasible and the burden of disease in the UK is concentrated in first generation immigrants.

<p>It is well-known that f-block elements can exhibit coordination modes which surpass those of the transition metals. With uranyl and uranium bis(imido) complexes a strong preference is shown for the oxo or imido ligands in the <i>trans-</i> position; a phenomenon which is known as the inverse trans- influence which is unique to high valent actinides. However, when a third imido is added to the complex, a decrease in bond order occurs and this preference is diminished. Through the synthesis of several novel coordination complexes of tris(2,6-diisopropylphenyl)imido uranium [U(NDipp)₃] with a variety of ligands, we were able to analyze the energy differentials between bonding modes in both the solution and solid state. Furthermore, density functional theory calculations were employed to model the energetic preferences between these geometries. The combination of analyses gives rise to the observation that the orientation of the imido substituents is fluxional depending on the rigidity of the supporting ligands, and oftentimes exhibits low energetic barriers for the formation of different conformers.</p> <p> Uranium tris(imido) species bearing <i>trans</i>-imidos are desirable synthons as they can be used to mimic reactivity of more complicated uranium oxide polymeric systems. Such systems are advantageous as they are easily soluble in organic solvents, making them amenable to standard characterization methods and ligand substitution strategies. Our group has previously shown that uranium tris(imidos), easily synthesized from [(^MesPDI^Me)U(THF)]₂ and various azides, feature axial imido substituents exhibiting differing bond characteristics than the adjacent equatorial imido substituent. The aim of this work is to show that multiple analogues of mixed imido products can be formed from either the aforementioned dimer or stable tris(imido) synthons by exploiting reactivity differences between the axial and equatorial positions. </p> Presented herein are novel copper-​catalyzed ring opening reactions of cyclopropanols and various electrophiles to synthesize a variety of beta-​functionalized ketones. The reactions feature mild conditions and tolerates a wide selection of functional groups leading to complex products which can be used in the synthesis of bioactive molecules.

Cannabis use among teenagers in Canada is a concern because of the long-term and irreversible effects cannabis has on the developing body and mind. Nurses can be instrumental in screening for cannabis abuse by implementing a tool to assess for substance use disorder (SUD) and triage drug users to appropriate treatment. This project focused on how to implement the CRAFFT screening tool while gaining insight of the practitioner's knowledge base about the tool and how SUD is being screened for, currently. The CRAFFT screening tool aligns with the DSM-IV's SUD diagnosis criteria, allowing for efficient identification of those at risk for SUDs. Rotter's social-behavioural learning theory is presented to provide a greater understanding of how one's environment affects SUDs. Sources of evidence were primary health care providers (N = 10) at the health centre where this project was conducted. Data were collected before and after the participants engaged in the learning module on the CRAFFT screening tool. A descriptive analysis found that being acquainted with the tool allowed health care providers to understand the significance of screening for cannabis use among young adults and teenagers and to have more detailed documentation of patients' relationships with cannabis. The screening tool was favoured by 90% of the participants for cannabis use assessment after learning about the tool with this project. Nine out of ten of the participants indicated that they will now use the tool to aide in identifying SUD. Once SUD has been identified with the use of the CRAFFT screening tool, 80% of the participants indicated that they would refer their patients for further assessment and treatment for this substance abuse, which would promote positive social change.

Most microbial organic molecules are secondary metabolites which consist of diverse chemical structures and a range of biological activities. Actinobacteria form a large group of Eubacteria that are prolific producers of these metabolites. The recurrence of pathogens resistant to antibiotics and a wider use of these metabolites apart from their use as anti-infectives, has been the impetus for pharmaceutical companies to search for compounds produced by rare and existing actinobacterial cultures. Accessing microbial biosynthetic pathway diversity has been possible through the use of sensitive and innovative molecular detection methodologies. The present study evaluated the use of molecular based screening as a rational approach to detect secondary metabolite biosynthetic genes (SMBG) in uncharacterised natural Actinobacterial populations. A polymerase chain reaction (PCR) approach was selected for ease of application and high sample processivity. Rational designed screening approaches using PCR in the discovery of SMBG, involved identifying common functions in secondary metabolite biosynthetic pathways, such as condensation reactions in polyketide synthesis, genes encoding these functions, and using conserved regions of these genes as templates for the design of primers to detect similar sequences in uncharacterised actinobacteria. Design of primers involved rigorous in silico analysis followed by experimentation and validation. PCR screening was applied to 22 uncharacterised environmental isolates, eight of these displayed the presence of the ketosynthase (KS) gene belonging to the type I polyketide synthases and eight contained the ketosynthase (KSĄ) gene belonging to the type II polyketide synthases, six of the isolates contained the presence of a presumptive dTDP-glucose synthase (strD) gene which is involved in the formation of deoxysugar components of aminoglycoside antibiotics and one isolate contained the presence of a presumptive isopenicillin N synthase (pcbC) gene involved in beta-lactam synthesis. Alignments of partially sequenced PCR products from isolates A1488 and A3023 obtained using type II PKS primers showed close similarities with KSĄ genes from antibiotic producing actinobacteria. Similarly, alignments of sequences from isolates A1113 and A0350 showed regions of similarities to KS genes from antibiotic producing actinobacteria. Fermentation techniques were used for inducing expression of secondary metabolites from the uncharacterised actinobacteria isolates. By using antimicrobial guided screening it was determined that most of the isolates possessed the capacity to produce antimicrobial metabolites. Dominant antagonistic activity was detected against Gram positive bacteria and to a minor extent against fungi. Optimal fermentation liquid media were identified for certain isolates for the production of antimicrobial metabolites. Two alternative fermentation methods; solid-state and liquid-oil fermentations were evaluated to improve secondary metabolite production in the uncharacterised isolates. Solid-substrate fermentation showed that it could induce a complex metabolite pattern by TLC analysis, however this pattern varied according to the substrate being used. Liquid media supplemented with refined oils, showed a positive response indicated by higher antibacterial activities detected. Evaluation of semi-purified organic extracts identified two isolates A1113 and A0350 producing similar antimicrobial metabolites as detected by HPLC/UV/MS, a literature database search of similar compounds containing the same molecular weight identified the compound as belonging to the actinomycin group of compounds. A complex metabolic pattern was identified for isolate A2381, database searching identified some of the compounds as having similar molecular weights to actinopyrones, trichostatins, antibiotics PI 220, WP 3688-5 and YL 01869P. Drug discovery screening can serve to benefit from PCR detection of biochemical genotypes in initial screens, providing a rapid approach in identifying secondary metabolite producing capabilities of microorganisms prior to the commencement of costly and time consuming fermentation studies. Additionally the identification of biochemical genotypes allows a directed approach in using fermentation media designed to induce biosynthetic pathways of specific classes of compounds.

In this work, we present mathematical and artistic techniques for the easy creation of artistic screening animations in video resolution by extending the artistic screening technique of adapting various patterns as screen dots for generating halftones. For video dithering, three different animations are needed. One is for screen dots which is a simple black and white animation; another is for the goal (or perceived) animation on the screen; and the other animation is for controlling the color and the size of screen dots. By combining three different animations with video dithering techniques, two animations appear simultaneously on the result video screen and provide complex and unique animation. Our techniques assure creating of aesthetic looking movies by providing frame to frame coherence and avoiding spatial and temporal aliasing that can be caused by low quality of video images. We shows how this technique is a powerful and effective way to create artistic results, by demonstrating variety of video dithering.