Dissertations / Theses on the topic 'Drug analysis'
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Mohiddin, Syed Basha. "Development of novel unsupervised and supervised informatics methods for drug discovery applications." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1138385657.
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Winter, David. "Drug analysis by mass spectrometry." Thesis, University of Canterbury. Chemistry, 1986. http://hdl.handle.net/10092/6560.
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1. The pharmacokinetics of morphine have been measured in four patients with renal failure and three healthy volunteers following intramuscular administration of papaveretum. Morphine blood levels were determined using GCMS with specific ion monitoring. The significantly shorter drug elimination half-life found for the patients suggests that renal failure does not impair the elimination of morphine.
2. A CI GCMS assay with specific ion monitoring has been developed for measuring the anti parkinsonian drug benztropine in post-mortem specimens. The assay is potentially more sensitive than a similar assay using electron impact ionisation.
3. The level of atropine in an aqueous extract of Datura stramonium has been measured by GCMS with selected ion monitoring. The results show that such an extract will contain most of the atropine present in the plant material. The levels are such that several medium sized glassfuls will contain sufficient atropine to constitute a dangerous drug dose.
4. A Hewlett-Packard 5982A GCMS has been successfully modified to allow it to be used to record in-beam mass spectra with a commercially available DCI probe. The effectiveness of these modifications is discussed and in-beam mass spectra of some physiologically active compounds are presented.
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Kimber, M. L. "Mass spectrometric methods in drug analysis." Thesis, Bucks New University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373602.
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Tuttle, Kimberly. "An Analysis of California Drug Courts: Why Drug Treatment Programs Should Have Teeth." Scholarship @ Claremont, 2019. https://scholarship.claremont.edu/cmc_theses/2124.
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Since the passing of Proposition 47 in California in 2014, drug court programs across the state have invariably undergone changes. In my thesis, I evaluate the drug court programs of three counties in Southern California: Orange County, Los Angeles County, and Riverside County. Through a qualitative analysis of the drug court programs in these counties, via interviews, data collection, and courtroom observation, I provide insight into the functionality of each county's program, as well as an analysis of the effects of Proposition 47. This paper aims to address the key factors involved in maintaining a functional and successful drug court system.
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Malm, Mikaela. "Drug Analysis : Bioanalytical Method Development and Validation." Doctoral thesis, Uppsala universitet, Analytisk kemi, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8547.
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This thesis describes bioanalytical methods for drug determination in biological matrixes, with drugs in focus used against diseases largely affecting low-income countries. Solid-phase extraction is used for sample cleanup, and processed samples are analyzed by liquid chromatography. Developed bioanalytical methods are validated according to international guidelines. Eflornithine (DFMO) is a chiral drug, used for treating human African trypanosomiasis. A bioanalytical method for determination of DFMO enantiomers in plasma is presented. The enantiomers are detected by evaporative light-scattering detection. The method has been applied to determination of D-DFMO and L-DFMO in rats, after intravenous and oral administration of racemic DFMO. It is concluded that DFMO exhibits enantioselective absorption, with the more potent enantiomer L-DFMO being less favored. Sulfadoxine (SD) and sulfamethoxazole (SM) are sulfa-drugs used for malaria and pneumonia respectively. Two methods are described for simultaneous determination of SD and SM in capillary blood sampled on filter paper. The former method allows direct injection of extracts from dried blood spots (DBS), while for the latter method solid-phase extraction is added. Pre-analytical factors contributing to measurement uncertainty is also discussed, and it is concluded that it is of high importance that homogeneity in type of sampling paper and sampling volume is assured. Piperaquine (PQ) is an antimalarial, increasingly used in artemisinin combination therapy. A method for determination of piperaquine in DBS is presented. By using a monolithic LC column, a very short LC analysis of two minutes per sample is achieved. A method for simultaneous determination of three antiretroviral drugs i.e. lamivudine (3TC), zidovudine (AZT) and nevirapine (NVP), in DBS samples is described. The method is applied to drug determination in two subjects after receiving standard antiretroviral treatment. Conclusion is that the method is suitable for determination of 3TC and NVP, and to some extent for AZT.
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Donoso, Barrera Alejandra. "Nanomechanical sensor arrays for antibiotic drug analysis." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/17276/.
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The increasing emergence of antibiotic-resistant bacterial strains, such as methicillin-resistant Staphylococci aeurus (MRSA) is driving the development of new technologies to investigate antibiotics. This thesis describes the use of BioMEMS cantilever technology for the label-free detection of glycopeptide antibiotics in solution, at concentrations as low as ~ 1 nM. Multiple cantilever arrays were used to detect the antibiotics vancomycin, ristomycin, chloroeremomycin and oritavancin, which are often considered as the ‘last line of resistance’ to bacterial infections. Cantilevers wee coated with thiolated mucopeptide analogues found in antibiotic-sensitive bacteria and mutated peptides found in resistant strains. Drug-mucopeptide binding was found to generate a compressive surface stress and could discriminate the deletion of a single hydrogen bond associated with resistant peptides. Measured binding constant were in close agreement with reported data. Building on these findings, a new model is proposed to describe the propagation of surface stress on cantilevers and considers two factors – a chemical binding factor describing local drug-target interactions and a factor describing the mechanical connectivity –percolation – of the system. These findings and underlying concepts will simplify the design of new coating and devices to significantly enhance drug detection sensitivity. The second part of this thesis describes two novel approaches to optimise microcantilever technology. The first approach investigates the role of the gold adhesion layer by comparing silane self-assembled monolayers with conventional chromium/titanium layers. The second approach describes finite element simulations of a novel silicon-metal hybrid strain gauge with gauge factors of up to 800 that could be used as an alternative to optical cantilever bending detection. Prototype strain gauges were fabricated and tested, where the measurements were shown to agree remarkably well with the simulations.
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Chow, Yat-ming Joe, and 周一鳴. "Policy analysis: school voluntary drug-testing scheme." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B46772625.
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García, Martín Meráz. "A theoretical approach : an exploratory analysis of higher level narcotraffickers of Latin American decent." Online access for everyone, 2007. http://www.dissertations.wsu.edu/Dissertations/Fall2007/M_Garcia_082007.pdf.
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Ng, Kwok-cheung. "An analysis of the anti-narcotics strategy in Hong Kong." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38598231.
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Ng, Yik-ying Katherine. "Risk factors an introduction to the sociopsychological analysis of drug use /." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38929004.
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Horne, Julie C. "A psychographic segmentation analysis of prescription drug users." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ27510.pdf.
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Mogalian, Erik. "Studies in Aerosol Drug Formulation, Analysis, and Modeling." Diss., The University of Arizona, 2008. http://hdl.handle.net/10150/194099.
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A recently mandated change in the use of pharmaceutical propellants spurred the development and reevaluation of aerosolized pharmaceuticals. Chlorofluorocarbon (CFC) propellants were commonly used in pressurized metered dose inhalers (MDIs), but were unfortunately linked to the depletion of the ozone layer. As such, a search for new propellants was initiated and ultimately resulted in the implementation of hydrofluoroalkane (HFA) propellants in MDIs. These HFA propellants however demonstrated significantly different properties than CFCs and necessitated a considerable amount of reformulation efforts. Not only did HFAs demonstrate different physiochemical properties, but in some cases these differences necessitated reengineering of the delivery device. Unfortunately HFA propellants are considered greenhouse gasses, albeit to a lesser degree than CFCs, so the development of alternate delivery methods has been ongoing. One delivery method that has received significant attention and resources is dry powder inhalers (DPIs). DPIs are a propellant-free alternative to aerosolized drug delivery, and demonstrate some advantages and disadvantages compared to the use of MDIs and nebulizers.In addition to the modernization of pharmaceutical agents, excipients, and delivery devices, technological advances have allowed for different and/or improved characterization of pharmaceutical aerosols. Particle size characteristics of aerosols are the primary physical measure examined and are relevant to ensure proper and reproducible drug delivery to the lung. Likewise, chemical analysis of the pharmaceutical agent is extremely important for pharmaceutical development and monitoring, including solubility determination, stability monitoring, and ultimately, dose emitted. Because many limitations exist in characterization however, and because experimental means can be costly with regard to labor and materials, prediction of aerosol performance characteristics based on formulation and device variables are valuable.Previous work predicting the performance of solution based MDIs has opened the door for improved prediction of suspension based MDI systems. Suspension aerosol prediction has been examined in the past, but additional information is now available to more appropriately model suspension MDI systems that include polydisperse drug material and emit polydisperse droplets.
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Hawkins, Paul Allen. "Regression analysis of oncology drug licensing deal values." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/37980.
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Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, September 2006."August 2006."
Includes bibliographical references (leaves 37-38).
This work is an attempt to explain wide variations in drug licensing deal value by using regression modeling to describe and predict the relationship between oncology drug deal characteristics and their licensing deal values. Although the reasons for large variances in value between deals may not be immediately apparent, it was hypothesized that objective independent variables, such as a molecule's phase, its target market size and the size of the acquiring/licensor company could explain a significant portion of variation in cancer drug values. This model, although not predictive when used independently, could be used to supplement other discounted cash flow and market based techniques to help assess the worth of incipient oncology therapies. Using regression analysis to study drug licensing deals is not novel: a study was published by Loeffler et al in 2002 that attempted to assess the impact of multiple variables on deal value in a wide range of pharmaceutical indications. The independent variables in Loeffler's work could explain less than 50% of differences in deal values. It was expected that refining the model could lead to improved regression R squared coefficient and, potentially, be a useful tool for managers. This current work is based on the 2002 Loeffler paper, but differs significantly by: * Focusing on just oncology licensing deals instead of deals covering many indications, * Incorporating a measure of the assets of the larger licensee company, * Accounting for the licensing experience of the smaller licensor company, * Factoring in inflation and the years the deals were signed; and * Assessing the impact of primary indication market size. The goal of the thesis was to advance the art of estimating the value of drug licensing deals by assessing the impact of the aforementioned factors.
by Paul Allen Hawkins.
S.M.
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Trim, Paul James. "MALDI-MS imaging for direct drug distribution analysis." Thesis, Sheffield Hallam University, 2009. http://shura.shu.ac.uk/20455/.
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MALDI Imaging has gained huge interest in the past few years with an ever increasing population of specialists choosing to investigate samples using MALDI imaging, including growing interest and financial backing from pharma and contract research organisations. Presented within this thesis is the development and application of MALDI imaging techniques for a variety of analytical problems. The use of various software packages have been employed in the interpretation of the data acquired from MALDI experiments including, the use of statistical analysis for the identification of ion of interest from 6 distinct brain regions and also for the identification of ions of interest associated with small molecule tumour markers. The advantages of MALDI-IMS-MSI as a further separation stage within MALDI-MSI have been shown. Demonstrated is a method for MALDI-IMS-MS imaging of endogenous lipids in healthy tissue and tumours, also demonstrated is the application of MALDI-IMS-MS to xenobiotic distribution studies, it has been clearly shown that ion mobility separation within MALDI-MSI experiments can improve the analysis of xenobiotics by removing any interfering ions. With instrumentation development for MALDI a high repetition rate Nd:YVO4 laser has been assessed as a possible method for decreasing acquisition time.
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Taylor, Sonya Dorothy Anne. "Genetic analysis of drug resistance in Trypanosoma brucei." Thesis, University of Glasgow, 2004. http://theses.gla.ac.uk/30898/.
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Genetic mapping, positional cloning and reverse genetics provide an alternative to the biochemical and molecular approaches used to date, to determine the basis of arsenical resistance in Trypanosoma brucei. Genetic mapping of loci determining phenotypes of relevance to diseases has proved to be a powerful approach in a number of organisms including humans and Plasmodium falciparum, particularly when coupled with a full genome sequence. In this thesis, this approach has been established in T. brucei by determining the genetic basis of naturally occurring arsenical resistance and undertaking linkage analysis using our recently developed genetic map. I adapted a simple, verified screening assay for assessing drug sensitivity based on the use of AlamarBlue. Three stocks used as parents in genetic crosses differed in drug sensitivity; STIB 247-Sensitive, STIB 386-Resistant and TREU 927-Resistant. Genetic linkage analysis using 101 polymorphic markers Identified from the extensive sequence available from the genome project was then used to examine inheritance of the drug resistance phenotype in T. brucei. From this, the co-segregation (into F1 progeny) of markers and the resistance phenotype was determined using crosses, 247 x 386 and 247 x 927. Inheritance of resistance in both crosses was compatible with a simple single locus genetic model with one dominant allele determining resistance. Linkage analysis showed that the locus conferring resistance lay within an ~25 kilobase region on Chromosome II, which contains 6 open reading frames (ORFs). A reverse genetic approach was then used to disrupt alleles for each of the six ORFs in turn. An allele of one gene, Tb927.2.2380, was shown to determine resistance and this was confirmed by transfecting the resistance allele into a drug sensitive stock to generate an arsenical resistant line. This gene also determines cross-resistance to the major veterinary trypanocide, diminazene aceturate and has been named the arsenical and diamidine (ard) resistance gene.
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Garibay, Luis K. "Theoretical Analysis of Drug Analogues and VOC Pollutants." Thesis, University of North Texas, 2016. https://digital.library.unt.edu/ark:/67531/metadc862850/.
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While computational chemistry methods have a wide range of applications within the set of traditional physical sciences, very little is being done in terms of expanding their usage into other areas of science where these methods can help clarify research questions. One such promising field is Forensic Science, where detailed, rapidly acquired sets of chemical data can help in decision-making at a crime scene. As part of an effort to create a database that fits these characteristics, the present work makes use of computational chemistry methods to increase the information readily available for the rapid identification and scheduling of drugs to the forensic scientist. Ab initio geometry optimizations, vibrational spectra calculations and ESI-MS fragmentation prediction of a group of common psychedelics are here presented. In addition, we describe an under development graphical user interface to perform ab initio calculations using the GAMESS software package in a more accessible manner. Results show that the set of theoretical techniques here utilized, closely approximate experimental data. Another aspect covered in this work is the implementation of a boiling point estimation method based on group contributions to generate chemical dispersion areas with the ALOHA software package. Once again, theoretical results showed to be in agreement with experimental boiling point values. A computer program written to facilitate the execution of the boiling point estimation method is also shown.
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Lalonde, Matthew Scott. "HIV Drug Resistance Polymorphism Analysis Using Ligase Discrimination." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1244059520.
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Hays, Faith A. "Mass spectrometric analysis of cytoplasmic ribosomal proteins in drug resistant and drug susceptible cell lines." College Park, Md. : University of Maryland, 2006. http://hdl.handle.net/1903/3725.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2006.Thesis research directed by: Biochemistry. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Watson, Davis. "Constitutionality of drug possession as a strict liability crime an analysis of florida's drug statute." Honors in the Major Thesis, University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/637.
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The United States has a drug issue that is perpetually problematic. Efforts are being made on every level of government to reduce drug use and deter current and potential future users. Some of these efforts however are putting citizen's rights at risk in a manner that threatens the United States Constitution that hails over both the state and federal governments. My thesis will examine Florida's avant-garde approach to simplifying drug convictions through unprecedented legislation that has already been ruled unconstitutional on its face by the United States District Court for the Middle District of Florida. The decade long struggle will soon culminate in the Florida Supreme Court, and if found unconstitutional, could potentially impact thousands of inmates among other legal consequences. Through literature review and case study I will discuss the history of this issue and conclude by discussing possible rulings of the Florida Supreme Court in State v. Adkins, SC11-1878 (2D11-4559, 2nd DCA). In addition, I will analyze the case timeline that led to the legislative action which is being called into question in Adkins. I hypothesize that the ruling in Adkins will declare Florida's drug statute unconstitutional; however, I further presume that the currently incarcerated defendants will continue to serve their sentences virtually unaffected by the ruling, with some extraordinary exceptions. First, I will discuss the underlying legal premises, succeeded by an analysis of all pertinent case law and literature to assess the constitutionality of Florida's drug statute to further support my hypothesis. My goal for this thesis is to give perspective to the layperson as well as contribute to the statewide legal community through my organization of the subject, and analysis of case law.B.A. and B.S.
Bachelors
Health and Public Affairs
Legal Studies
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Neal, Roderick Q. "The State of the Drug Court: A Systematic and Critical Analysis of Drug Court Evaluations." Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/29217.
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Drug courts have become an important part of adult and juvenile corrections. Since the establishment of the first adult drug court in 1989, the therapeutic court model has developed, and can now be considered a significant component in American criminal justice. The problem is adult drug courts have faced considerable disapproval in the area of evaluation and documentation. Through the Bureau of Justice Assistance (BJA), the federal government allots millions of dollars to support drug court programs; there have been attempts to count and record the activities of these programs with little success, there is little uniform data on actual drug court success nationwide.
The intent of this dissertation was to systematically and critically analyze drug court evaluations. My major goal was to demonstrate the need for uniformity in regards to assessing the impacts on outcomes. I analyzed drug court evaluations and their attempt to identify factors that contribute to graduation, in-program recidivism/ retention rates, drug treatment relapse and postprogram recidivism rates. Forty drug court evaluations were used in this examination. Further, I introduced a model that will aid in examining the impacts on outcome. My studies' unit of analysis is the evaluation report. I attempted to explain specific issues, such as how well drug courts work for different types of offenders. I was also able to generate a well founded policy recommendation for the evaluation of drug courts based on empirical data and literature. Conclusions show that Drug Courts do reduce post-program recidivism however there were certain impacts on graduation and termination rates. I also demonstrated the need for more methodologically sound and uniform evaluations in order to determine effectiveness.Ph. D.
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Todd, Douglas Wallace, and Douglas Wallace Todd. "Zebrafish Video Analysis System for High-Throughput Drug Assay." Thesis, The University of Arizona, 2016. http://hdl.handle.net/10150/623150.
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Zebrafish swimming behavior is used in a new, automated drug assay system as a biomarker to measure drug efficiency to prevent or restore hearing loss. This system records video of zebrafish larvae under infrared lighting using Raspberry Pi cameras and measures fish swimming behavior. This automated system significantly reduces the operator time required to process experiments in parallel. Multiple tanks, each consisting of sixteen experiments are operated in parallel. Once a set of experiments starts, all data transfer and processing operations are automatic. A web interface allows the operator to configure, monitor and control the experiments and review reports. Ethernet connects the various hardware components, allowing loose coupling of the distributed software used to schedule and run the experiments. The operator can configure the data processing to be done on the local computer or offloaded to a high-performance computer cluster to achieve even higher throughput. Computationally efficient image processing algorithms provided automated zebrafish detection and motion analysis. Quantitative assessment of error in the position and orientation of the detected fish uses manual data analysis by human observers as the reference. The system error in orientation and position is comparable to human inter-operator error.
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Gersper, Beth E. "NETWORK ANALYSIS OF DRUGS OF ABUSE IN OHIO AND POLICY IMPLICATIONS." University of Akron / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=akron156761393419992.
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Dhar, Sohini. "Religiosity, Spirituality and Attendance at Religious Services among Recreational Drug Users: A Sub-Analysis of the Drugnet Survey." TopSCHOLAR®, 2010. http://digitalcommons.wku.edu/theses/181.
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This study is a sub-analysis ofthe previously collected cross-sectional DRUGNET survey data. The sample included 1,178 current users of illicit drugs and 389 former users. This study was delimited to U.S. citizens, aged 18 years and older, who completed the DRUGNET survey (n =1,567). DRUGNET was a descriptive online survey of self - reported attitudes and behaviors among a group of adult, self - identified drug users (i.e., not drug abusers). The purpose of the sub-analysis was to explore the importance of religion, spirituality, and religious service attendance in the context of an otherwise normal healthy adult life. Moreover, it also looked into potential patterns of association between aspects of religiosity/spirituality and illicit drug use. The study explored if there was a relationship between the strength of a respondent's spiritual or religious beliefs and the patterns of their recreational drug use. A canonical correlation analysis was conducted using self-rated spirituality, self-rated religiosity, and attendance at services as variables on the left (entered in MANOVA as dependent variables) and self-reported use of six groups of drugs as variables on the right (entered in MANOV A as covariates). One significant function was found, which showed that attending religious services and importance of religion were negatively associated with the use of alcohol, marijuana, cocaine, and hallucinogens. That is, people who reported a higher level of religiosity and who attended religious services were less likely to use these psychoactive drugs.
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Watt, Alan Paul. "Liquid chromatographic and mass spectrometric methods for the chiral analysis of drugs and drug metabolites." Thesis, University of Hertfordshire, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421286.
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Hodder, Peter S. "Flow injection techniques for enzymatic and cellular drug discovery assays /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/8565.
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Thomason, Michael John. "The microbial chiral inversion of drug molecules." Thesis, University of Brighton, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284046.
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Rahbar, Amir Mikel. "Proteomic analysis of plasma membrane proteins from drug susceptible and drug resistant breast cancer cell lines." College Park, Md. : University of Maryland, 2004. http://hdl.handle.net/1903/1981.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2004.Thesis research directed by: Biochemistry. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Wang, Chen. "High-throughput prediction and analysis of drug-protein interactions in the druggable human proteome." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5509.
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Drugs exert their (therapeutic) effects via molecular-level interactions with proteins and other biomolecules. Computational prediction of drug-protein interactions plays a significant role in the effort to improve our current and limited knowledge of these interactions. The use of the putative drug-protein interactions could facilitate the discovery of novel applications of drugs, assist in cataloging their targets, and help to explain the details of medicinal efficacy and side-effects of drugs. We investigate current studies related to the computational prediction of drug-protein interactions and categorize them into protein structure-based and similarity-based methods. We evaluate three representative structure-based predictors and develop a Protein-Drug Interaction Database (PDID) that includes the putative drug targets generated by these three methods for the entire structural human proteome. To address the fact that only a limited set of proteins has known structures, we study the similarity-based methods that do not require this information. We review a comprehensive set of 35 high-impact similarity-based predictors and develop a novel, high-quality benchmark database. We group these predictors based on three types of similarities and their combinations that they use. We discuss and compare key architectural aspects of these methods including their source databases, internal databases and predictive models. Using our novel benchmark database, we perform comparative empirical analysis of predictive performance of seven types of representative predictors that utilize each type of similarity individually or in all possible combinations. We assess predictive quality at the database-wide drug-protein interaction level and we are the first to also include evaluation across individual drugs. Our comprehensive analysis shows that predictors that use more similarity types outperform methods that employ fewer similarities, and that the model combining all three types of similarities secures AUC of 0.93. We offer a first-of-its-kind analysis of sensitivity of predictive performance to intrinsic and extrinsic characteristics of the considered predictors. We find that predictive performance is sensitive to low levels of similarities between sequences of the drug targets and several extrinsic properties of the input drug structures, drug profiles and drug targets.
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McBride, Ali. "Evaluating Fast Track Time Analysis of Clinical Drug Trial Phases Utilizing a Quasi-Experimental Observational Study." The University of Arizona, 2007. http://hdl.handle.net/10150/624440.
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Class of 2007 AbstractObjectives: In this paper we analyzed the time frame for oncology drugs that were designated as a fast track drug and the time transition from a phase II to phase III clinical trial completion. Methods In our study we utilized oncology drugs that were approved between the years of 2000-2006 (FDA.gov). We then analyzed the CDER data base that provided information to Fast Track drugs that have been approved within the time period as determined by the FDA selection criteria (21 CFR 312.81(a)). Under certain circumstances, the FCA may consider reviewing portions of a marketing application in advance of the complete New Drug Application (NDA) or Biologic License Application (BLA). We will evaluate fast track designated products which may also be eligible to participate in FDA’s Continuous Marketing Applications Pilot 1 or Pilot 2 programs. For our analysis, we specifically selected oncology drugs. In particular, we analyzed 32 drugs from the stated time period. Each fast track drug was then selected and analyzed for its clinical phase development time period based on news announcements during clinical trails. For each announcement we conducted an event study analysis through lexis Nexus with respect to the announcement of a clinical trial enrollment, clinical trials news (Phase I, II, III). Results: The results of our preliminary study show that there was a shorter time to development transition for the fast track oncology drugs. The oncology clinical phase transition from II to three on average lasted 12 months with a range of 2 - 29 months The average length of the phase development had to excludes 4 drugs due to the lack of information provided from the LexisNexis database. The current timeline for fats track drugs has shown a decrease in transition from clinical trials to the market. In the example of Spyrcel, the data from our study had to be excluded, there was a definitive difference in the time to approval process for the drug as compared to other standard review entities. The approvals for dasatinib, or Sprycel, for refractory CML was shown to move through the development to approval in one of the fastest timeframes in modern development. Since its first clinical study on in Gleevec-resistant patients, the medication was decided on entering an accelerated timeline. It took us just 25 months to bring Sprycel from first-in-human dosing to a regulatory submission. In contrast, the industry average for this cycle time is 6.4 years which is three times greater than the cycle time for Sprycel. Conclusions: The new Subpart H regulations state that post-marketing studies to confirm clinical benefit that would consist usually by "studies underway” at the time of accelerated approval, this has not always been the case and is not a requirement (Dagher R, Johnson J, Williams G et al). In conclusion, the accelerated approval program in oncology has been successful in making 18 different products available to patients for 22 different cancer treatment indications since the inception of the fast track program. From the current data and transition information, there is a comparative difference between the clinical phase transitions from phase II to Phase III clinical trials. However, this preliminary data needs to be further evaluated against the standard FDA review process from oncology drugs. Moreover, further studies will be needed to interpret whether the average length of oncology studies biases the value of our study.
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Rufino, Stephen Duarte. "Analysis, comparison and prediction of protein structure." Thesis, Birkbeck (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243648.
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Boise, Geoffrey Loren. "A Qualitative Analysis of Substance Use and the Commission of Burglary." OpenSIUC, 2015. https://opensiuc.lib.siu.edu/theses/1721.
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The purpose of this thesis is to develop a more focused understanding of the role of substance use and burglary. The data for this effort comes from interviews that were collected by Richard T. Wright and Scott H. Decker. The data was obtained through extensive interviews with 105 active offenders, specifically offenders who were active at the time of interview, but also who were residential burglars. The interviews were informally conducted on an individual basis, and participants were assigned nicknames or aliases rather than using real names. The findings of this thesis revealed that substance use plays a modest role in burglary, as does the perception of how drugs altered the mental consciousness. In a test of drug-crime nexus arguments, this study examined this relationship through disinhibition, motivation of drug use, the existence of a shared space, and the association of a delinquent subculture. The role of narcotics and alcohol use are included in the analysis, as there are notable effects described by participants.
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Song, Shin Miin, and shinmiin@singnet com sg. "Comprehensive two-dimensional gas chromatography (GCxGC ) for drug analysis." RMIT University. Applied Sciences, 2006. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080627.114511.
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Separation technologies have occupied a central role in the current practices of analytical methods used for drug analysis today. As the emphasis in contemporary drug analysis shifts towards ultra-trace concentrations, the contribution from unwanted matrix interferences takes on greater significance. In order to single out a trace substance with confidence from a rapidly expanding list of drug compounds (and their metabolites) in real complex specimens, analytical technologies must evolve to keep up with such trends. Today, the task of unambiguous identification in forensic toxicology still relies heavily upon chromatographic methods based on mass spectrometric detection, in particular GC-MS in electron ionisation (EI) mode. Although the combined informing power of (EI) GC-MS has served faithfully in a myriad of drug application studies to date, we may ask if (EI) GC-MS will remain competitive in meeting the impending needs of ultra-trace drug analysis in the fut ure? To what extent of reliability can sample clean-up strategies be used in ultra-trace analysis without risking the loss of important analytes of interest? The increasing use of tandem mass spectrometry with one-dimensional (1D) chromatographic techniques (e.g. GC-MS/MS) at its simplest, considers that single-column chromatographic analysis with mass spectrometry alone is not sufficient in providing unambiguous confirmation of the identity of any given peak, particularly when there are peak-overlap. Where the mass spectra of the individual overlapping peaks are highly similar, confounding interpretation of their identities may arise. By introducing an additional resolution element in the chromatographic domain of a 1D chromatographic system, the informing power of the analytical system can also be effectively raised by the boost in resolving power from two chromatographic elements. Thus this thesis sets out to address the analytical challenges of modern drug analysis through the application of high resolut ion comprehensive two-dimensional gas chromatography (GCeGC) to a series of representative drug studies of relevance to forensic sciences.
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Broad, Barbara Patricia, and n/a. "An analysis of peer drug education : a case study." University of Canberra. Education, 1992. http://erl.canberra.edu.au./public/adt-AUC20060613.132241.
Full textAbstract:
Drug use and misuse by young people is a problem and concern in
the Australian and Australian Capital Territory (ACT) communities.
There are concerns regarding illicit and licit drugs but licit drug use
has been identified as the major area of concern. Young people in
the ACT reflect the drug use/misuse patterns and trends of other
states. Commonly used drugs by young people are alcohol, tobacco,
cannabis and analgesics.
Strategies to address the problem of drug use/misuse by young
people include intervention and community drug education programs.
Peer drug education (as an example of community drug education),
trains young people as peer educators to implement drug education
programs with younger age groups.
A case study analysis based on qualitative, naturalistic and new
paradigm research is the research method used in this thesis.
An eclectic model of drug education including key components from a
variety of drug education models provides a comprehensive overview
of peer drug education. The literature review showed the complexity
of influences on drug use/misuse. These influences relate to
individual, peer, parental and family, community and societal factors.
Peer drug education is generally recognised as an effective drug
education strategy.
Peer drug education programs (Triple T: Teenagers Teaching
Teenagers) were conducted in the ACT from 1988-1990. Reports
documenting these programs (including evaluation data) and a
literative review are the main data analysed for the case study.
The case study analysis of five ACT peer drug education programs
and one interstate program showed the key planning issues for
effective peer drug education were:
collaborative decision making as a central concept;
detailed planning and liaison with target groups;
established structures within schools and communities to
support the trained peer educators;
team work and small group work as intrinsic and extrinsic
factors within the program;
clarification of responsibilities and roles of all personnel
involved in the program; and
facilitators/leaders with attributes and qualities that encourage
peer drug educators as social change agents.
Analysis of data from the case study reports showed young people
can be effective peer drug educators. Residential programs are
preferred over non-residential programs. Peer drug education
programs are effective in both school and community agencies.
The literature review and analysis of reports also indicated that peer
drug education needs to focus on establishing positive norms in
groups of young people. Collaborative decision making and positive
role modelling assist in the establishment of these norms. Peer drug
education links to the wider changes occurring in education and
health settings. Peer drug education is about collaborative decision
making, social justice, development of key competencies and social
change.
This thesis confirmed the complexity and dynamic nature of peer drug
education and there were many questions raised for further research
from the literature review and analysis of program reports.
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Beerenwinkel, Niko [Verfasser]. "Computational Analysis of HIV Drug Resistance Data / Niko Beerenwinkel." Aachen : Shaker, 2004. http://d-nb.info/1170545238/34.
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Wong, Kai-chung Martin, and 王啟忠. "Policy analysis on youth drug abuse in Hong Kong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B46778299.
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Barrett, Sophie Victoria. "Analysis of drug resistance markers in primary breast cancer." Thesis, University of Glasgow, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433184.
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Farebrother, Joanna E. "Statistical design and analysis of factorial combination drug trials." Thesis, University of Reading, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264855.
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Sweeney, Patricia J. "NMR analysis of drug interactions with isotopically labelled calmodulin." Thesis, University of Hertfordshire, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303390.
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Wang, Qi. "Computational analysis of HIV-1 evolution and drug resistance." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1779690471&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Reiland, Joanne Elizabeth Donovan Maureen D. "Analysis of cell culture models of mammary drug transport." Iowa City : University of Iowa, 2009. http://ir.uiowa.edu/etd/316.
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Lekostaj, Jacqueline K. "Molecular analysis of membrane transporters implicated in drug resistance." Connect to Electronic Thesis (ProQuest) Connect to Electronic Thesis (CONTENTdm), 2008. http://worldcat.org/oclc/436214303/viewonline.
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Wonch, Wendy J. "Analysis of Variables Related to Drug and Alcohol Use." W&M ScholarWorks, 2002. https://scholarworks.wm.edu/etd/1539626378.
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Maass, Katie F. "Quantitative analysis of cellular processing of Antibody-Drug Conjugates." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/103185.
Full textAbstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2016.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Vita. Cataloged from PDF version of thesis.
Includes bibliographical references (pages 108-115).
Antibody-Drug Conjugates (ADCs) are a promising therapeutic class which combines the potency of chemotherapeutic drugs with the specificity of a tumor targeting antibody. ADCs aim to reduce systemic toxicity and maintain or improve therapeutic efficacy. Once an ADC reaches a tumor and binds its target antigen, it is internalized via receptor-mediated endocytosis. The ADC is internalized into an endosomal/lysosomal compartment, where the ADC is degraded, releasing the drug component from the antibody. The drug component can then leave the endosomal/lysosomal compartment and bind its intracellular target; hopefully, resulting in tumor cell killing. In this thesis, we focus on how ADCs get processed at a cellular level. First, we developed a flow cytometric clonogenic assay and used this assay to study the single-cell potency of the chemotherapeutic drug doxorubicin. Across a number of cancer cell lines, we found that a cell's ability to proliferate was only dependent on the amount of doxorubicin inside the cell and independent of varying drug media concentration, length of treatment time, or treatment with verapamil. We established a single-cell IC50 of 4 - 12 million doxorubicin molecules per cell. Next, we developed a model for ADC cellular processing and parameterized this model using a clinically approved ADC, T-DM1. Sensitivity analysis suggests that the amount of drug that is delivered to cells is a function of the amount of drug that comes in via internalization and the amount the leaves via drug efflux. This work also demonstrates how it is important to consider ADC processing as a complete system rather than isolating individual steps when designing ADCs. We also incorporated this cellular level processing model into a larger pharmacokinetic/pharmacodynamic model. Finally, we used fluorescence microscopy with a Trastuzumab-Doxorubicin ADC to track where within a cell the drug component traffics once released from the antibody. We find that the ADC does not deliver a significant number of doxorubicin molecules to the nucleus, suggesting that escape from the lysosome limits the amount of drug that can be delivered to its target via an ADC. The ability to escape the lysosome should be considered when designing an ADC.
by Katie F. Maass.
Ph. D.
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Al-Qallaf, Barrak. "Mass transfer analysis of transdermal drug delivery using microneedles." Thesis, University of Oxford, 2009. http://ora.ox.ac.uk/objects/uuid:19b5221f-f3a6-4fd6-9263-2eecd39acfcd.
Full textAbstract:
Microneedle is a promising technique for delivering high molecular weight drugs across skin. The microneedles can offer a number of benefits over other drug delivery methods. For example, the drugs only diffuse over a short distance before reaching the blood circulation which enhances the absorption of drugs by the tissue. However, the drug transport behaviour in skin is affected by a complex interplay of many parameters (e.g., microneedle geometries, permeability across skin, etc). In this thesis, many aspects of the microneedle field were examined. A mathematical model for drug transport from microneedle systems into skin was developed. Issues such as microneedle penetration, surface area of the microneedle arrays, etc. were investigated. This work helped us to focus into optimizing the design of microneedles by developing an in-house algorithm to enhance the performance of transdermal drug delivery using microneedles. Following the development of this algorithm, the influence of skin thickness with its classification (i.e., age group, race, etc.) on drug permeability across skin was studied. Attention was then given to determine the effective permeability (Peff) and the effective skin thickness (Heff) for various solid microneedle models. The outcome of this research allowed us to study the influence of microneedle dimensions on the drug concentration in blood (Cb). Furthermore, the 'pattern' (shape) of the microneedles array (i.e., square or rectangular) and the 'distribution' (arrangement) of the microneedles inside an array (i.e., triangular or diamond) were investigated to identify the optimum microneedle models. Finally, the effect of skin metabolism on both the patch (without microneedles) and the microneedle arrays on drug intake were examined.
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Garcia, Agnes D. "The use of capillary electrophoresis (CE) in drug analysis." FIU Digital Commons, 2005. https://digitalcommons.fiu.edu/etd/3928.
Full textAbstract:
Capillary electrophoresis is currently a very powerful technique for the analysis of seized drugs. A rapid analytical CE method for the screening and quantification of GHB and GBL was achieved using 300mM CTAC/25mM phosphate buffer pH 6.3. Reversed phase HPLC was achieved using 25mM phosphate buffer pH 6.5 and a Cl8 Aqua column. Chiral separation of 9 amphetamine type stimulants was obtained using a highly sulfated gamma-cyclodextrin as a chiral selector. MECC and CZE were compared for the analysis of psilocybin, while a rapid and robust method is presented for the analysis of major opium alkaloids, using dynamically coated capillary columns. The column is coated with a polycation followed by a polyanion coating, using a commercial reagent kit. Using a background electrolyte pH of 2.5 with the addition of hydroxypropyl-beta- cyclodextrin and dimethyl-beta-cyclodextrin, the analysis of morphine, papaverine, codeine, noscapine, and thebaine in opium samples was obtained with great resolution. Finally, separation of common benzodiazedpines was also investigated using CZE and a pH 2.5 phosphate buffer.
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Reiland, Joanne Elizabeth. "Analysis of cell culture models of mammary drug transport." Diss., University of Iowa, 2009. https://ir.uiowa.edu/etd/316.
Full textAbstract:
A human-derived, mammary epithelial cell culture model would allow drug transport in the mammary epithelium to be studied in greater detail while minimizing risks to mothers and nursing infants. MCF10A and primary human mammary epithelial cells (HMECs) were investigated for their utility as human, cell-based model systems for drug transport studies. Polarized monolayers are essential for transcellular flux studies of drug transporter function, and their formation was measured by transepithelial electrical resistance, immunofluorescence microscopy and vectoral flux studies. Both cell types failed to form adequately polarized monolayers despite various modifications to the cells or culture conditions.
Transporter-mediated drug uptake and efflux in MCF10A cells was measured using flow cytometry, a technique which enables the measurement of intracellular drug concentrations. The fluorescent drug, mitoxantrone, was used to assess active efflux transport by the ABC transporters ABCG2 (BCRP) and ABCB1 (MDR1). After accounting for the inter-day variability with a linear mixed effects model, inhibitor effects on intracellular drug concentrations were evident. Specific inhibition of MDR1 using verapamil increased mitoxantrone accumulation as expected; however, BCRP-specific inhibition with fumitremorgin C decreased accumulation. Flow cytometry studies on mitoxantrone uptake suggested that it is a substrate for an unidentified active uptake transporter.
PEPT1 and PEPT2 transporter functionality in MCF10A cells was evaluated using a fluorescently labeled dipeptide (A-K-AMCA). A-K-AMCA uptake showed an active component which was inhibited by a general metabolic inhibitor, the dipeptide Gly-Gln, and the peptidomimetic cefadroxil, indicating the involvement of a peptide transporter in A-K-AMCA uptake.
Drug transporter expression levels in MCF10A cells and HMECs were measured using RT-PCR. Transporter expression levels, which were similar in the MCF10A cells and the HMECs, were compared with expression levels in lactating and non-lactating mammary epithelial cells. Low expression of BCRP, MDR1 and PEPT1 was seen in MCF10A cells, yet the effects of these transporters could still be observed in functional flow cytometry transport assays. Flow cytometry studies MCF10A cells may useful as a mammary drug transport model for transporters which have similar expression levels to lactating mammary epithelial cells.
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Yacoub, Kimberly. "Development of ESI-LC-MS Method for Drug Analysis." Cleveland State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=csu1524040258129489.
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MacDonald, Ziggy. "An analysis of illicit drug use in the UK." Thesis, University of Leicester, 2001. http://hdl.handle.net/2381/30136.
Full textAbstract:
The subject of this thesis is illicit drug use in the UK. Given the wide-ranging implications of illicit drug consumption, it is surprising that the UK government collects very little national data to monitor drug use, and this is despite making a commitment to reducing consumption (and its consequence) in its Ten-Year Drugs Strategy (Home Office, 1998). This is the main concern of this concern of this thesis. In particular, the aim is to explore the nature of the currently available UK data on illicit drug use and the extent to which it can be used to address a number of policy concerns. The analysis presented in this thesis is unique in the UK context, as it would appear to be the first to have considered illicit drug use from an economics perspective using UK data. The conclusions emanating from this analysis have implications for public policy and, perhaps more importantly, for the generation of information required to support policy formation. However, in reviewing the current literature one conclusion of the thesis is that policy makers and drug researchers do not appear to have fully recognised the important role for economic analysis in their work, and there is generally a lack of appreciation of the role of detailed price information in studying the demand for illicit drugs. Beyond this, issues of inadequate data provision have been explored in this thesis and improvements to current information provision suggested, and in part acted upon by the Home Office. The thesis has shown that the British Crime Survey (BCS) questions only allow us to observe a limited number of drug use states, despite this survey being the main source of national drug misuse information in the UK. In considering the inadequacies of the current data, one conclusion of this thesis is that a modest redesign of the questionnaire would overcome the inherent observational problem arising from the current design at little extra cost to survey administration.
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Peterson, Dana Mark. "Preventing drug abuse in the Navy : an analysis of effectiveness and efficiency /." Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 1994. http://handle.dtic.mil/100.2/ADA292847.
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Kaali, Reuben Nicodemus. "Studies of the physicochemical properties, dissolution and bioavailability of glibenclamide." Thesis, University of Bradford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281117.
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