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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Cost-Effectiveness of UGT1A1 Genotyping Prior to Irinotecan Therapy

Berryman, Lindsay, Cameron, Caitlin 2007 (has links)
Class of 2007 Abstract Objectives: The objective of this study was to determine the cost-effectiveness of using the Invader® UGT1A1 Molecular Assay to identify patients at risk of experiencing neutropenia from irinotecan monotherapy and FOLFIRI. Methods: Publicly available search engines were used to search for literature reporting the rate, treatment, and cost of adverse events and the population rate of genotypes. Drug acquisition costs were determined using average wholesale prices. Additional costs were determined using the Physicians’ Fee and Coding Guide. Monte Carlo Simulations were performed to reveal average cost, average effectiveness, and 95% confidence intervals. Tornado diagrams were derived to identify variables most likely to affect the outcomes and sensitivity analyses. Results: Monte Carlo simulations of monotherapy revealed a mean cost of treatment with genotype assay information of $6,620 (SD: $3,235; 95% CI: $5,408 to $15, 258) and an effectiveness ratio of 0.877 (SD: 0.328; 95% CI: 0 to 1). Without the genotype assay information the mean cost of treatment was $7,358 (SD: $4,183; 95% CI: $5,083 to $14,883) and the effectiveness ratio was 0.764 (SD: 0.425; 95% CI: 0 to 1). Monte Carlo simulations of FOLFIRI data showed a mean cost of treatment with genotype assay information of $6,105 (SD: $3,438; 95% CI: $4,706 to $14,556) and an effectiveness ratio of 0.858 (SD: 0.349; 95% CI: 0 to 1). When genotype information was unknown, the mean cost of FOLFIRI was $6,833 (SD: $4,288; 95% CI: $4,331 to $14,181) and the effectiveness ratio was 0.746 (SD: 0.435; 95% CI: 0 to 1). Conclusions: Genotyping patients exposed to irinotecan monotherapy or FOLFIRI may be a cost-effective means of identifying at risk patients but the results from this study while favorable are not statistically significant.
12

Espécies de Cryptococcus obtidas de isolados clínicos e ambientais da cidade de Campinas, SP : genotipagem e avaliação da suscetibilidade "in vitro" frente a agentes antifúngicos isolados e em diferentes combinações Cryptococcus species obtained from clinical and environmental isolates from the city of Campinas, SP : genotyping and assessment of in vitro susceptibility of antifungal agents alone and in different combinations

Franqueline Reichert Lima 2014 (has links)
Resumo: O gênero Cryptococcus engloba duas espécies consideradas patogênicas: C.neoformans e C.gattii. Apesar dos avanços na área médica, a criptococose permanece uma das infecções fúngicas sistêmicas mais importantes no Brasil. Anfotericina B (AMB) associada a flucitosina (5FC) é a terapia de indução indicada porém, no Brasil, 5FC não está disponível e o tratamento segue somente com AMB ou em associação com fluconazol (FCL). Este trabalho avaliou a ocorrência de espécies e os genótipos de isolados clínicos de pacientes atendidos no Hospital de Clínicas da UNICAMP em um período de 5 anos; isolados ambientais coletados na cidade de Campinas-SP e o perfil de suscetibilidade aos antifúngicos sozinhos contra isolados clínicos e ambientais e o efeito de combinações de antifúngicos frente a isolados clínicos de Cryptococcus spp.. A identificação de espécies e genótipos foi realizada por testes bioquímicos, Restriction Fragment Length Polymorphism do gene URA5 (URA5-RFLP) e sequenciamento da região Internal Transcribed Spacer (ITS) do DNA ribossomal. Testes de suscetibilidade para AMB, 5FC, FCL, voriconazol (VRC), itraconazol (ITC) e terbinafina (TRB) isolados foram realizados conforme CLSI M27-A3 (2008). Os testes com antifúngicos combinados (AMB+5FC; AMB+FCL; AMB+TRB; FCL+TRB), foram realizados pelo método do ''tabuleiro de xadrez'' para determinação do Coeficiente de Inibição Fracional (CIF) para avaliar o tipo de interação entre as substâncias (sinergismo, indiferença ou antagonismo). Dentre 75 isolados clínicos reativados, foram identificados 66 C.neoformans e 9 C.gattii. Todos C.gattii pertenceram ao genótipo VGII enquanto que 62 isolados de C.neoformans ao genótipo VNI e apenas 4 ao genótipo VNII. Foram obtidos 92 isolados ambientais de Cryptococcus, pertencentes às espécies C.neoformans (genótipo VNI), C.laurentii, C.albidus, C.flavescens e Cryptococcus spp.. Os valores dos intervalos de CIM para C.neoformans clínicos foram AMB: ≤ 0,125-1 μg/mL; 5FC: ≤ 0,125-2 μg/mL; FCL: 0,25-8 μg/mL; VRC: ≤ 0,015-0,125 μg/mL; ITC: 0,03-0,25 μg/mL e TRB: 0,125-2 μg/mL. Intervalos de CIM para C.gattii variaram de 0,25-1 μg/mL para AMB; 0,5-4 μg/mL para 5FC; 2-16 μg/mL para FCL; 0,06-0,25μg/mL para VRC; 0,06-0,5 μg/mL para ITC e 0,5-4 μg/mL para TRB. Foram observados elevados valores de CIM para os antifúngicos 5FC e FCL frente aos isolados ambientais de C.albidus e C.laurentii. O genótipo VNI de C.neoformans clínico mostrou 75,80% de interação sinérgica para AMB+5FC; 79,03% para AMB+FCL; 77,42% para AMB+TRB e 95,16% para FCL+TRB. O genótipo VNII apresentou 100% de sinergismo em todas as combinações. C.gattii (VGII) apresentou 88,9% de sinergismo nas combinações AMB+5FC e AMB+FCL; 100% para AMB+TRB e FCL+TRB. Não foi observado efeito antagônico nas combinações de antifúngicos. Foi observado bom desempenho nas combinações realizadas, especialmente naquelas envolvendo a TRB para ambas as espécies C.neoformans e C.gattii. O genótipo VNI foi o predominante entre os genótipos que afetam os pacientes com criptococose na região de Campinas. Em infecções de difícil tratamento ou que não respondem aos antifúngicos convencionais, a combinação de diferentes antifúngicos como AMB+TRB ou FCL+TRB podem vir a ser uma alternativa em países onde 5FC não está disponível, como no Brasil. Mais estudos são necessários para avaliar o papel dos genótipos na sensibilidade aos antifúngicos, assim como estudos de combinações de antifúngicos in vitro e in vivo para que novas estratégias possam ser empregadas no tratamento da criptococose. ;;Abstract:Cryptococcus genus comprises two species considered pathogenic: C.neoformans and C.gattii. Despite advances in the medical field, cryptococcosis remains one of the most important systemic fungal infections in Brazil. Amphotericin B (AMB) associated with flucytosine (5FC) induction therapy is indicated but, in Brazil, 5FC is not available and treatment follows only with AMB or in combination with fluconazole (FCL). This study evaluated the prevalence of species and molecular subtypes of clinical isolates from patients treated at the Hospital of UNICAMP in a period of 5 years; environmental isolates collected in Campinas – SP and in vitro antifungal susceptibility profile of antifungal agents alone against clinical and enviromental isolates of Cryptococcus spp. and the effect of combinations of antifungal agents against clinical isolates of Cryptococcus spp.. The species identification and subtyping was performed by biochemical tests, Restriction Fragment Length Polymorphism of URA5 gene (RFLP - URA5) and sequencing of the Internal Transcribed Spacer region (ITS) of ribosomal DNA. Susceptibility tests for AMB, 5FC, FCL, voriconazole (VRC), itraconazole (ITC) and terbinafine (TRB) isolated were performed according to CLSI M27-A3 (2008). Combined antifungals tests (AMB +5FC; AMB+FCL; AMB +TRB, FCL+TRB), were performed by the "Checkerboard" method to determine the Fractional Inhibitory Coefficient index (FIC) to assess the type of interaction between substances (synergism, indifference or antagonism). Among the 75 viable clinical isolates, 66 were identified as C.neoformans and 9 as C.gattii. All C.gattii belonged to subtype VGII while 62 isolates belonged C.neoformans VNI genotype and only 4 VNII. 92 environmental isolates of Cryptococcus were obtained. The species C.neoformans (subtype VNI) C.laurentii, C.albidus, C.flavescens and Cryptococcus spp.were identified. The MIC range values of clinical C.neoformans for AMB were: ≤ 0.125 -1 μg/mL; 5FC: ≤ 0.125 to 2 μg/mL; FCL: 0.25-8 μg/mL; VRC: ≤ 0.015 to 0.125 μg/mL; ITC: 0.03 to 0.25 μg/mL and TRB: 0.125 to 2 μg/mL. MIC for C.gattii ranged from 0.25-1 μg/mL for AMB; 0.5-4 μg/mL for 5FC; 2-16 μg/mL for FCL; 0.06 to 0.25 μg/mL for VRC; 0.06 to 0.5 μg/mL for ITC and 0.5-4 μg/mL for TRB. High MIC values were observed for FCL and 5FC against environmental isolates of C.albidus and C.laurentii. The VNI C.neoformans genotype showed 75.80 % of synergistic interaction for AMB+5FC; 79.03 % for AMB + FCL; 77.42 % for AMB + TRB and 95.16 % for FCL+TRB. The VNII genotype showed 100% synergism in all combinations. C.gattii (VGII) showed 88.9 % of synergism in combinations AMB+5 FC and AMB+FCL; 100 % for AMB+TRB and TRB+FCL. No antagonistic effect was observed in all evaluated antifungal combinations. Good performance was observed in all combinations performed, especially those involving TRB for both C.neoformans and C.gattii species. The VNI was the predominant genotype among genotypes affecting patients with cryptococcosis in Campinas region. In difficult to treat infections or unresponsive to conventional antifungal agents, the combination of different antifungals so as AMB+FCL or TRB+TRB may become an alternative in countries where 5FC is not available, as in Brazil. More studies are needed to evaluate the role of genotypes in sensitivity to antifungal agents, as well as antifungal agents combination studies in vitro and in vivo so that new strategies can be employed in the treatment of cryptococcosis.
13

Prevalence and molecular characterization of \kur{Cryptosporidium} spp. in dairy cattle in South Bohemia, the Czech Republic Prevalence and molecular characterization of \kur{Cryptosporidium} spp. in dairy cattle in South Bohemia, the Czech Republic

ONDRÁČKOVÁ, Zuzana 2009 (has links)
The prevalence and molecular characterization of Cryptosporidium spp. in slaughtered cattle 6 months and older was performed. Three species of Cryptosporidium were identified. A subtype of C. parvum was obtained.
14

Pharmacogenomics of solute carrier transporter genes in the Xhosa population

Jacobs, Clifford Winston 2014 (has links)
Philosophiae Doctor - PhD Solute carrier transporters belonging to the major facilitator family of membrane transporter are increasingly being recognized as a possible mechanism to explain inter-individual variation in drug efficacy and response. Genetic factors are estimated to be responsible for approximately 15-30% of inter-individual variation in drug disposition and response. The aims of this study were to determine the minor allele frequencies of 78 previously identified single nucleotide polymorphisms in the pharmacogenetically relevant SLC22A1-3 and SLC47A1 genes in the indigenous African population of South Africa. Secondly, to determine whether allele and genotype frequencies for these SNP were different from that reported for other African, Caucasian, and Asian populations. Thirdly, to infer haplotypes from the genetic information which can potentially be used in future to design and interpret results of pharmacogenetics association studies involving these genes and their substrate drugs. Finally, to determine whether the Xhosa population harbour novel SNPs in the SLC22A2 gene, that encodes the kidney-specific hOCT2. SNaPshot™ multiplex single base minisequencing systems were developed and optimized for each of SLC22A1, SLC22A2, SLC22A3, and SLC47A1 covering the previously identified 78 SNPs. These systems were then used to genotype the alleles of 148 healthy Xhosa subjects residing in Cape Town, South Africa. In addition, the proximal promoter region and all 11 exons and flanking regions of the SLC22A2 gene of 96 of the participants were screened for novel SNPs by direct sequencing. The Xhosa subjects investigated lacked heterozygosity and were monomorphic for 91% of the SNPs screened. None of the SLC22A3 and SLC47A1 SNPs investigated was observed in this study. Sequencing of the SLC22A2 gene revealed 28 SNPs, including seven novel polymorphic sites, in the 96 Xhosa subjects that were screened. The minor allele frequencies of the seven previously identified variant SNPs observed in this study were different compared to that observed for American and European Caucasian, and Asian populations. Moreover, the allele frequencies for these SNPs differed amongst African populations themselves. Eight and seven haplotypes were inferred for SLC22A1 and SLC22A2, respectively, for the Xhosa population from the information gathered with SNaPshot™ genotyping. This study highlights the fact that African populations do not have the same allele frequencies for SNPs in pharmacogenetically relevant genes. Furthermore, the Xhosa and other African populations do not share all reduced function variants of the SLC22A1-3 and SLC47A1 genes with Caucasian and Asian populations. Moreover, this study has demonstrated that the Xhosa population harbours novel and rare genetic polymorphisms in the key pharmacogene SLC22A2. This study lays the foundation for the design and interpretation of future pharmacogenetic association studies between the variant alleles of the SLC22A1-3 and SLC47A1 genes in the Xhosa population and drug disposition and efficacy.
15

Drug mutation patterns and risk factors associated with patients failing first-line antiretroviral therapy regimen in Oshikoto and Oshana regions, Namibia

Shiningavamwe, Andreas Ndafudifwa 2015 (has links)
Magister Public Health - MPH HIV/AIDS is a major health problem in Namibia with HIV prevalence estimated at 18.2% among pregnant women. Antiretroviral therapy (ART) was introduced in the public sector in 2003 and ART roll out was expanded throughout the country in the subsequent years. There are 221 ART sites in Namibia which include 34 district hospitals and 187 outreach service points. Currently there are 127,486 patients registered on ART in Namibia. However, there have been cases of patients experiencing treatment failure. The treatment failure can give rise to the emergence of HIV drug resistance. Genotyping information from patients with treatment failure can be valuable for tracking the dominant mutations conferring HIV drug resistance. However, HIV genotyping is not routinely available in Namibia due to cost. It is essential to determine the risk factors associated with development of HIV drug resistance so that these factors can be addressed. The aim of the current study was to describe HIV drug resistance mutations and the risk factors associated with HIV drug resistance among patients failing first- line ART regimen in Oshikoto and Oshana regions in Namibia. The case-control study design was used to collect data from cases who were being suspected of treatment failure to the first–line regimen in Oshikoto and Oshana regions in Namibia. The demographic, clinical and genotype information was collected from patient records. Out of 168 cases, 97 cases were eligible for this study and were matched with 105 controls. The mean age was 44.8 (±13.2) years for controls and 43.3 (±13.3) years for cases. Cases from Oshana and Oshikoto regions harboured 63% and 71% respectively for nucleoside reverse transcriptase inhibitors mutations with the dominant mutation being M184V/I. Sixty-eight percent (68%) and 76% respectively harboured mutations for non-nucleoside reverse transcriptase inhibitors with dominant mutation being K103N. Missed appointments, initiating inappropriate first-line regimen and adverse events or side effects were identified as risk factors for virological failure with odd ratios (OR) of 21.58 (95% CI 6.50 -71.59); 11.70 (95% CI 1.69 - 80.99) and 7.17 (95% CI 1.89 -27.22) respectively. Patients failing the first-line regimen need to be genotyped to assess the development of HIV drug resistance. The patients initiating ART should be educated on impacts of missing clinical appointments and adverse events of the drugs in order to prevent the emergence of drug resistance.
16

Single nucleotide polymorphism association studies of ABCA13 and ABHD11 genes and the bioinformatics analysis of the autism candidate genes localized on chromosome 7

Davids, Muneera 2016 (has links)
>Magister Scientiae - MSc Autism, Aspergers Syndrome and Pervasive Developmental Delay-Not Otherwise Specified (PDD-NOS), among others, fall under an umbrella of disorders known as Autism Spectrum Disorder. Twin studies show that autism is a highly heritable disorder. More than 100 genes have been implicated in the aetiology of autism, each of which is involved in numerous biological processes and a variety of molecular interactions. William-Beuren syndrome is a multisystem developmental disorder caused by the deletion of contiguous genes at the 7q11.23 position. The aims of this study were (i) to genotype three SNPs (rs10279013, rs2293484 and rs17060) in the ABHD11 and ABCA13 genes, respectively, using Taqman® SNP Genotyping assays to detect association with autism in three distinct South African (SA) ethnic groups (Black, Caucasian and Mixed), and (ii) to ascertain common pathways or regulating transcription factors for genes on chromosome 7 that may attribute to it being an “autism hotspot”. Chapter 3 objectives were to identify potential candidate genes using STRING analysis and the Gene Cards database. The Taqman® study indicated significant association for SNP rs2293484 in the South African Caucasian group, as well as for the G allele in the South African Mixed group, where p<0.001. STRING analysis yielded 2 new candidate genes, FZD1 and FZD9. It was also found that the Wnt pathway in mammals plays a significant role in both ASDs and cancer, and there is a definite link between genes regulating cancer, and genes implicated in autism. The study provides evidence for not only the association of the investigated SNP in a South African population, but also provides evidence for the co-morbidity of several neurological and psychological disorders such as depression and bipolar disorder with autism.
17

The Molecular Epidemiology of Tuberculosis in South Carolina, 2005-2011: Estimates of Recent Transmission and Risk Factors for Genotype Clustering

Roach, Amy Kathleen 1 January 2017 (has links)
Because tuberculosis (TB) is a public health threat that continues to elude elimination in the United States, there is a need to identify contributing factors that may have implications for targeted control measures. Molecular studies of genetic clustering are crucial for pinpointing these contributing factors. It is for this reason this study was conducted. This was a non-experimental, cross-sectional population-based molecular epidemiological study of TB in SC from 2005 to 2011. Its purpose was to estimate the proportion of TB that may be due to recently acquired infection and to determine the risk factors associated with the genetic clustering of identical M. tuberculosis isolates from TB patients in South Carolina from 2005-2011. The analysis sample included 627 confirmed pulmonary and/or pleural cases of TB, for which complete data on all covariates and a valid genotype were available. The results strongly suggested that about 50% of TB in South Carolina is recently transmitted. The study also revealed that being born in the United States and Black race were independently and significantly associated with being part of a TB genotype cluster. The key messages of this study were as follows: a substantial portion of TB in South Carolina is due to recent transmission, not reactivation or importation, and transmission of TB in South Carolina occurs in groups often defined by American birth and Black race. These important findings indicate that most TB in South Carolina is preventable and that enhanced TB control efforts should be explored. The implication for positive social change is that employing targeted contact investigation informed by these findings could lead to decreased disease transmission. Future studies should explore pilot programs that investigate alternatives to the traditional TB contact investigation.
18

APPLICATIONS OF THE HARDY-WEINBERG PRINCIPLE TO DETECTION OF LINKAGE DISEQUILIBRIUM AND GENOTYPING ERRORS IN THE CONTEXT OF ASSOCIATION STUDIES

Londono-Vasquez, Douglas 8 June 2007 (has links)
No description available.
19

Genetic Study of Compositional and Physical Kernel Quality Traits in Diverse Maize (Zea mays L.) Germplasm

Ryu, Si Hwan 2010 (has links)
No description available.
20

Reading DNA with PNA : a dynamic chemical approach to DNA sequence analysis

Bowler, Frank Ray 2011 (has links)
Single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) constitute important sources of genetic variation which provide insight into disease aetiology and idiosyncratic differences in drug response. The analysis of such genetic variation relies upon the generation of allele-specific products, typically by enzymatic extension or the hybridization of allele-specific DNA probes. Herein, a distinct enzyme-free, dynamic chemistry-based method of producing allele-specific products for genotyping was developed. The approach was initially demonstrated in model systems using synthetic DNA, which was used as a template in a base-filling reductive amination reaction on a PNA backbone. The templated dynamic reaction between a free secondary amine at a ‘blank’ position on the PNA strand and four aldehyde-modified nucleobases drove selective formation of the ‘correct’ iminium intermediate according to Watson-Crick base-pairing rules. In a blind trial, the method was extended to genotype twelve cystic fibrosis patients for two mutations (one SNP and one indel) linked to this disease. Enzyme-free dynamic chemistry thus permitted successful genotyping in both singleplex and duplex formats, demonstrating the application of dynamic chemistry as a distinct method of allelediscrimination with certain advantages over those reported previously. The application of this method as a tool for the discovery of non-natural nucleobases with improved properties for antisense and genotyping applications was also investigated. Furthermore, progress was made towards the use of dynamic chemistry as a means of full nucleic acid sequence analysis, through the templated sequence-selective extension of PNA probes by reductive amination.

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