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A System Dynamics Evaluation of SARS Preventing Policies in TaiwanLo, Yu-tang 24 July 2004 (has links)
The research desires to evaluate the preventing policies on emerging infectious diseases by system dynamics, and takes the SARS situation in Taiwan for example. According to epidemiology and everything about SARS, we build the model of SARS transmission and prevention. Therefore we can simulate the situation and policies, and find the effective policies.
After the simulation and the evaluation, we find that most SARS patients at later stage are affected in hospital. For the reason, the most effective policies are the ¡uPolicy about enhancing protection abilities in hospital¡v and ¡uPolicy about reducing the interaction with people in hospital¡v. Furthermore, the effectiveness of ¡uQuarantine policies¡v is not stronger than the above policies. The most important thing is that we discover Taiwan is very lucky, because the infectivity is very low (about 3.7%). If the infectivity of SARS were as high as 10% and we still took the same policies as we took in 2003, the situation would be terrible. Anyway, when we confront this kind of emerging infectious diseases, the better way is taking policies in hospital intently.
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Applications of Optimal Control Theory to Infectious Disease ModelingHANSEN, ELSA K S 26 January 2011 (has links)
This thesis investigates the optimal use of intervention strategies to mitigate the spread of infectious diseases. Three main problems are addressed:
(i) The optimal use vaccination and isolation resources under the assumption that these resources are limited. Specifically we address the problem of minimizing the outbreak size and we determine the optimal vaccination-only, isolation-only and mixed vaccination-isolation strategies.
(ii) The optimal use of a single antiviral drug to minimize the total outbreak size, under the assumption that treatment causes de novo resistance.
(iii) The optimal use of two antiviral drugs to minimize the total infectious burden. Specifically we address the situation where there are two different strains and each strain is effectively treated by only one drug. / Thesis (Ph.D, Mathematics & Statistics) -- Queen's University, 2011-01-25 19:59:17.263
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Using electronic methods of adherence monitoring and therapeutic drug monitoring (TDM) to eliminate discordance between antiretroviral adherence and virological failureOrrell, Catherine January 2016 (has links)
Background: Adherence to antiretroviral therapy (ART) is critical: only 70% achieve viral suppression at a year. Current adherence methodologies, with slow reaction to missed dosing, inadequately predict virological outcomes. Ideal adherence methods would be cheap, easy to use, and allow rapid response to missed doses to improve outcomes. We explored ideal adherence monitoring methodology for a large public sector ART clinic in Cape Town. Methods: We designed a randomised controlled study for ART-naïve individuals to determine whether text messaging after a missed dose would improve adherence recorded by an electronic adherence monitoring device (EAMD), reduce treatment interruptions or impact on virological outcome (using regression modelling). Five other measures of adherence were captured prospectively during the study: selfrecall (SR), clinic-based pill count (CPC), pharmacy refill data (PR-average or PR-gaps) and efavirenz concentration. The predictive value of each adherence methodology on virological and HIV-1 resistance outcomes was compared by calculating the area under the receiver operating characteristic curve, from logistic regression models. The impact of efavirenz concentration and CYP2B6 metaboliser genotype data on failure was examined using Cox proportion hazard modelling; and the most predictive lower limit for EFV concentration was determined. Antiretroviral cohort and pharmacy refill data were compared, using simple statistics, to determine which provided the best method of determining those retained in care.
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Optimization of Cryopreserved Memory CD4 T Cell Mediated Protection against Lethal Influenza A Virus Infection in MiceAlam, Fahmida 01 January 2020 (has links) (PDF)
Interventions for influenza virus infections are essential to minimize the worldwide annual morbidity, mortality, and economic loss caused by this highly contagious respiratory pathogen. Establishment of universal, long-lasting protection against epidemic and pandemic strains of the virus can potentially eradicate the necessity of annual reformulation and readministration of low-efficacious seasonal vaccines, increasing pandemic preparedness. The protective potential of Type 1 T helper (TH1)-polarized memory CD4+ T cells against Influenza A virus (IAV) infection and generation of secondary memory populations following viral clearance are well-characterized. To assess the potential of CD4+ T memory cells as a candidate for adoptive immunotherapy, here we validated and optimized cryopreserved IAV-specific memory CD4+ T cell-mediated protection against infection and evaluated their potential for subsequent memory formation. Donor-derived in vitro-generated memory CD4+ T cells were transferred into IAV-infected naïve mice following cryopreservation of these cells for 6-12 months and overnight activation with gamma-chain cytokines, interleukin (IL)-7 and IL-7+IL-2. Results showed that cytokine-cultured cryopreserved memory CD4+ T cells, compared to their non-cultured counterparts, controlled viral titer in the lung at the peak infection phase, decreased morbidity, expedited recovery, and formed increased secondary memory cells in the lung, the primary site of infection, including lung tissue-resident memory (TRM) CD4+ T cells. Phenotypic and functional analysis confirmed that donor-derived secondary memory CD4+ T cells retain a TH1-phenotype and produce cytokines associated with protection against IAV. These observations support that the protectiveness and memory-forming potential of host- and/or donor-derived memory CD4? T cells can be preserved and harnessed for future use. This T-cell based adoptive immunotherapy addresses some of the current challenges of available preventative and therapeutic options, such as low vaccine efficacy, availability of only early treatment drugs, lack of immunity against pandemic strains and effective memory cell generation.
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EXPERIMENTAL EVIDENCE FOR COMPETITIVE COEXISTENCE OF TWO SPECIES OF PNEUMOCYSTIS WITHIN RAT LUNGSICENHOUR, CRYSTAL RENEE PERRY 30 January 2002 (has links)
No description available.
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Climate Predictors of Global Influenza Seasonality in Temperate and Tropical PopulationsTamerius, James Derek January 2011 (has links)
The consistent seasonal signal that characterizes annual influenza epidemics has long suggested a causal link between the physical environment and the transmission of influenza. Yet, despite considerable interest--dating as far back as Hippocrates--the environmental factors that facilitate the seasonal spread of influenza remain unclear. Historically, significant study of influenza seasonality was based almost exclusively on temperate regions,.due to a lack of high-quality influenza data in low-latitudes. In turn, although numerous hypotheses have been forwarded to explain the seasonal nature of influenza in temperate regions, few acknowledge the seasonal patterns in lower latitudes.This dissertation examines the scientific evidence for the seasonal mechanisms that potentially explain the complex seasonal patterns of influenza disease activity across the latitudinal gradient extending from temperate to tropical regions. I identified seasonal climatic variables that are potentially responsible for influenza seasonality from observational, experimental, ecological and anecdotal studies. I then used a global database of influenza seasonality to assess the consistency of relationships between influenza seasonality and the seasonality of relevant climatic variables. I determined that no single climatic variable is consistently correlated with seasonal influenza activity across temperate, subtropical and tropical regions.However, I did find a significant U-shaped relationship between specific humidity and influenza epidemics globally with epidemics becoming increasingly likely as specific humidity increases or decreases from approximately 12 g/kg. Further, I examined the temporal and spatial variation of influenza activity and specific humidity during the 2009 A/H1N1 pandemic across Mexico, which spans temperate, subtropical and tropical regions. I show that specific humidity may have modified the progression of three distinct waves of infection during the pandemic. These patterns are in agreement with the U-shaped relationship between specific humidity and seasonal influenza epidemics observed at a global scale. In all, this is the first time that relationships between climate and influenza (both seasonal and pandemic) activity have been successfully synthesized into a single parsimonious model across temperate, subtropical and tropical regions.
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Cholera in post-earthquake Haiti: how an outbreak became an epidemicBeydoun, Malk 24 October 2018 (has links)
Cholera in Haiti has persisted since its introduction after the 2010 earthquake. The outbreak demonstrates how a combination of socioeconomic factors, mainly a lack of infrastructure, can cause an outbreak to become a much more serious epidemic and the current enduring endemic. Because cholera came to a previously unexposed nation through United Nations peacekeepers, the outbreak in Haiti offers a unique perspective on the impact of globalization on public health. In addition, it provides a deeper look into the disproportionate impact of diarrheal diseases on low-income countries. Several biological and socioeconomic factors have facilitated the outbreak. Biological risk factors include immunologically naïve populations, low gastric acidity, and blood type. In addition, socioeconomic factors include a lack of clean drinking water and sanitation as well as a fragile and over-taxed healthcare system. The persisting struggle surrounding water and sanitation combined with a lack of knowledge on cholera prevention have precipitated the outbreak into an epidemic and further into its current endemic status. Current efforts to battle cholera include water and sanitation improvements, a national vaccination campaign, as well as the mobilization of community health workers. However, without the construction of sustainable water and sanitation infrastructure, it is unlikely that cholera in Haiti can be eliminated.
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Role of the Swain-Langley and McCoy polymorphisms in complement receptor 1 in cerebral malariaSwann, Olivia Veronica Fowell January 2018 (has links)
Malaria has been a major driving force in the evolution of the human genome. In sub-Saharan African populations, two neighbouring polymorphisms in the Complement Receptor 1 (CR1) gene, named Swain-Langley (Sl2) and McCoy (McCb), occur at high frequencies, consistent with selection by malaria. This thesis investigates the association between these two polymorphisms and severe malaria. Previous studies into this area have produced conflicting findings. Using a large case-control study of severe malaria in Kenyan children and statistical models adjusted for confounders, I found that the Sl2 polymorphism was associated with markedly reduced odds of cerebral malaria and death, while the McCb polymorphism was associated with increased odds of cerebral malaria. I also identified an interaction between Sl2 and α+thalassaemia, with the protective association of Sl2 greatest in children with normal α-globin. Following these epidemiological findings, I explored potential biological hypotheses which might explain them. The first approach examined whether the Sl2 and McCb polymorphisms affected how CR1 forms clusters on erythrocyte membranes, a process which is key in the binding and transfer of immune complexes from erythrocytes to macrophages. Using erythrocytes from Kenyan children, I performed immunofluorescence assays (IFAs) with confocal microscopy to quantify CR1 cluster number and volume. I found no association between the Sl2 and McCb polymorphisms and either the number or volume of CR1 clusters formed. The second approach investigated whether the cerebral malaria-specific associations seen with Sl2 and McCb might be due to expression of CR1 by human brain endothelial cells (HBEC). The immortalised cell line HBEC-5i was investigated for expression of CR1 using IFA, flow cytometry, western blotting, functional C3b degradation assays, mass spectrometry, immunoprecipitation and siRNA knockdown experiments. A pool of α-CR1 monoclonal antibodies recognised an intracellular antigen in permeabilised HBEC-5i cells which was a similar molecular weight to CR1 on western blotting. However, when the α-CR1 monoclonal antibodies were tested individually, only E11 recognised an HBEC-5i antigen. Further investigative approaches did not support the presence of CR1 on HBEC-5i cells, instead suggesting that E11 was not specific for CR1 and was instead recognising a protein in the Golgi apparatus. The final approach was to examine whether the Sl2 and McCb polymorphisms might influence the binding of the complement components mannose binding lectin, C1q and L-ficolin to the LHR-D region of CR1. I aimed to generate recombinant proteins of the LHR-D region which included the polymorphisms. Site-directed mutagenesis of the region was successful and subcloning and expression of the mutant amplicons will be performed at a later date. In summary, I have identified opposing associations between the Sl2 and McCb polymorphisms and cerebral malaria, which do not appear to be due to differences in CR1 clustering or expression of CR1 by human brain endothelial cells. My investigation into whether the polymorphisms might influence complement component binding is ongoing.
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Dynamics of the host-parasite interaction: in vitro correlates of Crassostrea-induced modulation of Perkinsus marinus functionEarnhart, Christopher G. 01 January 2004 (has links)
Perkinsus marinus is an alveolate protozoan parasite of the eastern oyster (Crassostrea virginica) which is responsible for much of the decline in United States oyster populations. Perkinsus marinus can be cultured in vitro, but is rapidly attenuated in the process. Supplementation of a protein-free medium with oyster products altered proliferation, changed protease expression in the parasite extracellular products (ECP), induced morphological forms typically seen in vivo, and partially reversed parasite attenuation. Supplements derived from dissected oyster tissues were used to determine if these changes could be differentially elicited. These supplements, with the exception of adductor muscle, reduced proliferation. Whole oyster and digestive gland/gonad supplements favored palintomic, rather than binary, fission. The total ECP protease activity was generally decreased in supplemented cultures, though gill/mantle supplements may have induced proteases. A low molecular weight subset of proteases was upregulated most effectively by heart- and adductor muscle-derived supplements. Serine proteases and other ECP proteins may be virulence factors. Attempts to create antibodies to study P. marinus cells and ECP have been largely unsuccessful due to poor immune responses and crossreactivity. Ultrafiltration-concentrated P. marinus ECP were poorly immunogenic and toxic to experimental animals. Immunogenicity was not substantially affected by heat denaturation or proteolytic inhibition. Co-administration of ECP with oyster plasma caused a suppression in the anti-plasma antibody response with restriction of epitope recognition. Analysis of medium constituents revealed that a surfactant, Pluronic F-68 (PF68), was immunosuppressive. Although isolated protein antigens from the ECP remained immunosuppressive, separation of the antigens from PF68 enabled antibody production. Five monoclonal antibodies were created against ECP from unsupplemented medium and were used to study ECP function, regulation, and mechanism of storage and release. ECP are secreted by release from the cell wall and from two morphologically distinct intracellular compartments. A sandwich ELISA allowed quantification of an ECP protein with significantly reduced expression in supplemented cultures. Another antibody, which specifically bound to trophozoite and tomont walls, was used to investigate morphological and antigenic changes during thioglycollate-induced formation of prezoosporangia, and confirm supplement-induced formation of prezoosporangia. This antibody labeled P. marinus cells in fixed oyster tissue in a species-specific manner.
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Tonsil Cell Products which Modify in Vitro Proliferation of Blood LymphocytesHodge, Thomas W. 01 May 1982 (has links)
Human palatine tonsil lymphocytes, when compared to peripheral blood lymphocytes (PBL), were in an activated state even though there was no in vitro stimulation. When these tonsil lymphocytes were cultured in the absence of serum and polyclonal mitogens or antigens, the supernatant fluid often inhibited the proliferative response of target PBL to con A. The extent of this suppression ranged from 22% to 84%, and target cell viability was 90% or greater. There was no evidence for the presence of immunoglobulins or (alpha)2-macroglobulin in whole supernatant fluids. The suppressor was partially denatured at 80(DEGREES)C and was rendered completely inactive upon exposure to 100(DEGREES)C for 5 min. It was trypsin sensitive, and had an apparent molecular weight of 100,000 or greater. The protein adhered strongly to DE-52 cellulose, and the most active material eluted with 0.4-0.6 M NaCl. The suppressor was active in the pH range 5.0 (+OR-) 0.6 as demonstrated by isoelectric focusing. Occasionally, supernatant fluids comprised material which augmented the expected response of con A stimulated PBL. The augmentor was 30,000 in molecular weight and was eluted from DE-52 cellulose in the 0.15-0.25 M NaCl range. Nearly all supernatant preparations tested contained a mitogenic substance which stimulated naive allogeneic human PBL without the necessity of co-stimulation by a mitogen. The mitogenic factor (MF) behaved in a dose dependent fashion and was evidently different from the augmentor since the MF stimulated PBL independently of lectin co-stimulation.
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