在此篇論文中，我們提出一個慢性Ｂ型肝炎病毒感染病程之數學模型。因為在病症間的轉移機率(Transition probability)是隨著患者的年齡變動，所以在過去的文獻中，已經有學者提出，在疾病轉移機率模型中，應加入國民生命表(Life table)，藉此讓機率模型更符合Ｂ型肝炎病患的生命歷程。但是過去的文獻中，學者並沒有利用加入國民生命表之後疾病模型做進一步的病程分析。在這篇論文當中，我們假設原始的疾病轉移模型是符合馬可夫鏈的性質，並且提出一種加入國民生命表的方法，賦予疾病有年齡相關特性之模型。根據文獻數據和類馬可夫機率性質，我們使用著名的Chapman-Kolmogorov公式計算Ｂ型肝炎的自然病程機率，並畫出病人的生存機率曲線(Survival curve)。文章最後將會藉由兩個例子來介紹此篇論文提出的模型。實驗數據結果證實，此模型不僅提供了一個更精確的方法去分析在病症與死亡間的轉移機率、平均餘命(Life expectancy)、以及在不同年齡的存活機率(Survival probability)，並且可以更進一步的分析且瞭解病情狀態之間的轉移狀況。 / In this thesis, we propose a new mathematical model extending the natural history of hepatitis B virus (HBV) prognosis progression on chronic HBV infection. Since the actual transition probabilities between symptoms are dependent of ages, it has been proposed that the life table should be accommodated to the HBV prognosis progression model so that it can more properly explain the disease progression of the HBV patients. But in the literature, no further disease analysis and applications of it with the life table are discussed. In this thesis, we assume that the original disease progression is described by a Markov model, and propose a new method to combine the HBV progression with the life table so that the proposed model integrates data from the life table and allows the accommodation of age-dependent properties of the target disease. With clinical data based on annual incidence rates, the entire model is Semi-Markov based in nature. Computation methods similar to the celebrated Chapman-Kolmogorov equation can be applied to study the associated probability of each likely trajectory with desired initial ages and health states under the scenarios of natural history and various treatment policies. This method provides a more accurate way to analyze the transitions between symptoms, such as the mean life expectancy or the survival probabilities at different ages. We will give examples to demonstrate the proposed method in this thesis. Numerical results show the proposed model not only provides a more accurate method to analyze the mean life expectancy, the survival probabilities at different ages, and the transition probabilities from symptoms to death but also helps us to understand the transitions between symptoms.

Water infrastructures have been implemented to support the vital activities of human society. The infrastructure developments at the same time have interrupted the natural catchment response characteristics, challenging society to implement effective water resources planning and management strategies. The Telemark area in southern Norway has seen a large number of water infrastructure developments, particularly hydropower, over more than a century. Recent developments in decision support tools for flood control and reservoir operation has raised the need to compute inflows from local catchments, most of which are regulated or have no observed data. This has contributed for the motivation of this PhD thesis work, with an aim of improving runoff estimation at ungauged catchments, and the research results are presented in four manuscript scientific papers.  The inverse distance weighting, inverse distance squared weighting, ordinary kriging, universal kriging and kriging with external drift were applied to analyse precipitation variability and estimate daily precipitation in the study area. The geostatistical based univariate and multivariate map-correlation concepts were applied to analyse and physically understand regional hydrological response patterns. The Sobol variance based sensitivity analysis (VBSA) method was used to investigate the HBV hydrological model parameterization significances on the model response variations and evaluate the model’s reliability as a prediction tool. The HBV hydrological model space transferability into ungauged catchments was also studied.  The analyses results showed that the inverse distance weighting variants are the preferred spatial data interpolation methods in areas where relatively dense precipitation station network can be found.  In mountainous areas and in areas where the precipitation station network is relatively sparse, the kriging variants are the preferred methods. The regional hydrological response correlation analyses suggested that geographic proximity alone cannot explain the entire hydrological response correlations in the study area. Besides, when the multivariate map-correlation analysis was applied, two distinct regional hydrological response patterns - the radial and elliptical-types were identified. The presence of these hydrological response patterns influenced the location of the best-correlated reference streamgauges to the ungauged catchments. As a result, the nearest streamgauge was found the best-correlated in areas where the radial-type hydrological response pattern is the dominant. In area where the elliptical-type hydrological response pattern is the dominant, the nearest reference streamgauge was not necessarily the best-correlated. The VBSA verified that varying up to a minimum of four to six influential HBV model parameters can sufficiently simulate the catchments' responses characteristics when emphasis is given to fit the high flows. Varying up to a minimum of six influential model parameters is necessary to sufficiently simulate the catchments’ responses and maintain the model performance when emphasis is given to fit the low flows. However, varying more than nine out of the fifteen HBV model parameters will not make any significant change on the model performance.  The hydrological model space transfer study indicated that estimation of representative runoff at ungauged catchments cannot be guaranteed by transferring model parameter sets from a single donor catchment. On the other hand, applying the ensemble based model space transferring approach and utilizing model parameter sets from multiple donor catchments improved the model performance at the ungauged catchments. The result also suggested that high model performance can be achieved by integrating model parameter sets from two to six donor catchments. Objectively minimizing the HBV model parametric dimensionality and only sampling the sensitive model parameters, maintained the model performance and limited the model prediction uncertainty.

[Truncated abstract] Around 50,000 hip and knee replacements are performed every year in Australia and this number has been increasing by around 13% annually since 1998 (Transplantation Society 2006). The incidence and number of revision surgery has increased by a similar proportion. Autogenous bone or allograft is still the gold standard grafting material and is currently used in a variety of reconstructive surgical procedures. The use of any allograft material carries with it the risk of transfer of disease from donor to recipient. These tissues can transmit the same viral and bacterial infections as blood, and the products of a single donation may be transplanted to several recipients. In contrast to blood, musculoskeletal tissues may come from surgical and cadaveric donation. Overall, the prevention of infection relies on the maintenance of rigid protocols for procurement, donor and allograft testing, secondary sterilisation, and the adherence to internal safety standards within the tissue banks. This thesis aims to determine the risk of viral infection among musculoskeletal tissue donors in Australia. We retrieved and analysed data retrospectively from three large tissue banks in Australia (Perth, Queensland, Victoria). This includes 12,415 musculoskeletal tissue donors, 10,937 of which are surgical donors and 1,478 of which are deceased donors, for the period of 1993 -2004. This data was analysed to determine the prevalence and incidence of viral infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) in musculoskeletal allografts. The results indicate that the risk of viral infection from musculoskeletal tissue transplantation in Australia is low. ... The results indicate that the overall prevalence of screened transfusion-transmitted viral infections did not vary significantly for musculoskeletal donors over the study period, despite falling in the general population and first-time blood donors. In tissue donors, HIV incidence significantly decreased over time, and HBV decreased significantly during 1999-2001; however, there was an apparent increase in the estimated incidence of HCV in 2002-2004 compared with earlier years. Furthermore the residual risk estimate of HIV in the period 2002-2004 has declined 5-fold compared to estimates in the period 1993-1995. This is perhaps due to greater awareness of high risk behaviours among donors, improvement in donor recruitment and an overall decrease in infection levels in the general population. Musculoskeletal tissue is second only to blood as the most frequent transplanted human tissue. Viral infection is a potential complication of tissue transplantation. In this thesis the rates of HIV, HBV, HCV and HTV infection in musculoskeletal donors in Australia were identified and then compared with results in published data from Canada, Scotland and the United States. The study also compared that result with first-time blood donors because they have satisfied similar donor selection criteria (Galea et al. 2006). The results indicate that prevalence and incidence estimates for viral infection in Australian tissue donors are higher than those in blood donors. This was also reported in studies from other countries. Accordingly, it is crucial that viral prevalence and incidence be monitored to evaluate the safety of tissue supply and to improve donor selection processes.

Project title: Optimalization of the regime of marker's examination of clinically important infections in blood donors Project author: Daniela Dušková, M.D. Project supervisor: prof. Vladimír Tesař, M.D., Dr.Sc., MBA, FASN The aim of this project is to contribute to the discussion about introducing the methods of molecular biology into the routine blood donor testing in the transfusions departments in the Czech Republic. The theoretical part includes a brief history and some turning points in transfusion medicine. The next part within the theoretical section is dedicated to the problems of infectious diseases concerning transfusion and the general examination processes used during the selection of blood donors. The end of the theoretical part concentrates on existing possibilities of markers' examination of clinically important infections in blood donors, including the list of processes performed in the Czech Republic, the European Union and other countries. The practical part describes this study, ie. the routine screening test of blood donors using the CMIA method (a routine method) and using RT-Real Time PCR method (a molecular biology method) for detecting infectious markers (HCV, HBV, HIV). Within this part, the principle of both methods and the process of actual examinations are described in...

Introduction International guidelines endorse the screening of patients for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and Chlamydia trachomatis before assisted reproductive techniques (ART). At present no such guidelines exists in South Africa. At the Reproductive and Endocrine Unit (referred to as “the Unit”) of Steve Biko Academic Hospital, all patients with unknown HIV status are counselled and a blood sample is collected during the initial visit for automated laboratory based HIV screening. These HIV results are not available before semen samples are processed. Furthermore, patients are not screened for HBV, HCV and Chlamydia trachomatis. Couples attending the Unit are of a low to middle socio-economic status and experience financial constraints. Moreover, automated laboratory based assays are expensive to perform. Rapid testing is a cost effective and practical method from screening patients, with a 20–30 minute result turnover time. Until screening at the Unit is improved, the possible identification of semen characteristics that could indicate HIV infection would be a useful tool. Materials and Methods The following rapid point-of-care assays were evaluated: Determine® HIV-1/2 combo test (n=100), Determine® HBsAg test (n=100), DIAQUICK HCV kit (n=74), and the DIAQUICK Chlamydia trachomatis kit (n=30). For profiling, parameters from a basic semen analysis of HIV-positive males (n=60) were compared with HIV-negative males (n=60). Information pertaining to CD4 count, antiretroviral treatment and plasma viral load of HIV-positive males were analysed. Results From all patients included in the study, 8% tested positive for HIV. The risk of a female being HIV-positive was 3.73 times higher than for males. In the pilot study to explore rapid testing for HBV and HCV, 1% and 1.4% of patients tested positive respectively. When testing for Chlamydia trachomatis 31.3% of females, but no males tested positive. Comparing semen profiles, no significant differences were found between samples from HIV positive and negative males or between HIV positive males categorised by CD4 cell count (p>0.05). For the HIV-positive group with a detectable plasma HIV viral load (>40 copies/ml), a significant difference was observed in the semen viscosity (p=0.0460). Significant differences were noted in the sperm motility (immotile sperm p=0.0456, progressive sperm p=0.0192) of patients receiving antiretroviral (ARV) therapy. Discussion and Conclusion The use of rapid testing is an acceptable and feasible option for improving current screening protocols at the Unit. The absence of definite alterations in the semen characteristics of HIV-positive men further motivates the need for a simpler, point-of-care screening protocol. The prevalence of HBV was lower than that reported in the general population of South Africa and further investigation is needed. Although the sample size was small, HCV prevalence was similar to that of the general population. One third of females tested positive for Chlamydia trachomatis. The methodology used was possibly not appropriate for males. This study highlighted the need for guidelines that address the specialised needs of ART clinics in resource-limited and developing countries with a high HIV prevalence. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Obstetrics and Gynaecology / unrestricted

MSc (Microbiology) / Department of Microbiology / Background: Prostate cancer (PCA) is a major health concern in males, particularly those above 40 years old. It is the most common form of cancer in males worldwide, including South Africa. In South Africa, the rate of histologically diagnosed prostate cancer is 40 per 100 000 in whites and 14 per 100 000 in blacks, and 1 in 8 men will develop PCA in their lifetime. Several reports have suggested the association of viruses in the pathogenesis of prostate cancer. Objectives: This study was aimed at identifying Hepatitis B virus (HBV), human papilloma virus (HPV) and human herpes virus type 8 (HHV-8), implicated in other forms of cancer, in a cohort of South African patients with either PCA or benign prostatic hyperplasia (BPH); and to seek possible associations thereof. Methods: The study group comprised 187 male patients recruited from Polokwane Hospital presenting with either PCA (staged by Gleason scores) or BPH. Enzyme-linked immunosorbent assay was used to detect antibodies to HHV-8 and HPV; and to detect hepatitis B surface antigen (HBsAg) in the plasma of the study subjects. Total DNA was extracted from plasma and targeted for the identification of HBV and HHV-8 DNA by nested PCR protocols. The HBV nested PCR protocol amplifies a 336bp fragment of the overlapping surface polymerase gene of HBV. The HHV-8 nested protocol amplifies a 233bp fragment of the ORF 26 gene of HHV-8. Amplified DNA products were purified, sequenced by the Sanger protocol and phylogenetically analysed for viral genotypes. The Chi-square test was used to infer statistically significant differences in the level of detection of viruses and the stage of prostate cancer development. Results: Of the 187 participants, a seroprevalence of 4.8% (9/187, HBsAg), 5.3% (10/187, HPV IgG antibody) and 27% (33/124, HHV-8 IgG antibody) were observed. HBsAg was detected more in individuals with BPH than those without and this was statistically significant at ( 2=6.0, p< 0.05). HHV-8 DNA was detected more in individuals in the 60-79 years age range and this was statistically significant at ( 2=61.1, p< 0.05). Occult HBV infection (that is the presence of HBV DNA in the absence of HBsAg) was detected in 23/178 (12.9%) of patients. Taking into account occult HBV infection, the overall prevalence of HBV was 17.7%. HBV genotype E was more prevalent (86.7%) followed by genotype A (13.3%). HHV-8 genotypes K and R were inferred. Apparently, this is the first report on the identification of HHV-8 genotypes K and R from South Africa. Conclusion: The current study has demonstrated for the first time, the presence of genotypes K and R of HHV-8 in South Africa. This study also suggests that there is a high level of occult genotype E HBV infection. Future studies will explore the virome in prostate cancer biopsies.

Project title: Optimalization of the regime of marker's examination of clinically important infections in blood donors Project author: Daniela Dušková, M.D. Project supervisor: prof. Vladimír Tesař, M.D., Dr.Sc., MBA, FASN The aim of this project is to contribute to the discussion about introducing the methods of molecular biology into the routine blood donor testing in the transfusions departments in the Czech Republic. The theoretical part includes a brief history and some turning points in transfusion medicine. The next part within the theoretical section is dedicated to the problems of infectious diseases concerning transfusion and the general examination processes used during the selection of blood donors. The end of the theoretical part concentrates on existing possibilities of markers' examination of clinically important infections in blood donors, including the list of processes performed in the Czech Republic, the European Union and other countries. The practical part describes this study, ie. the routine screening test of blood donors using the CMIA method (a routine method) and using RT-Real Time PCR method (a molecular biology method) for detecting infectious markers (HCV, HBV, HIV). Within this part, the principle of both methods and the process of actual examinations are described in...

M. Tech. (Department of Biotechnology, Faculty of Applied and Computer Sciences), Vaal University of Technology. / Background: Currently, the South African National Blood Services are not testing for HTLV and HTLV screening is not mandated by the WHO or by regulatory standards in South Africa. Looking at the uniquely high prevalence of HIV and HIV / HBV co-infections in the South African population and taking into account the literature that suggests that most of these infected patients will be receiving blood, exposing these patients to an additional burden like HTLV can result in an increased disease progression of HIV to AIDS and a poor prognosis in these infected patients. Study design and methods: A blinded cross-sectional study was performed. 7015 specimens were collected from all blood transfusion laboratories across South Africa excluding the Western Cape Blood Transfusion Service laboratories. The specimens collected were tested using the ABBOTT Alinity S® Immunochemiluminescent autoanalyser. All test results were confirmed with the Roche Cobas® E801 and E411 auto analyser. Results: Over all prevalence for HIV was 39.39% (N=2763), HBV 7.57% (n=531) and HTLV 0.70% (N=49). Concurrent infection for HIV/HBV 4.92% (N=345), HIV/HTLV 0.36% (N=25), HBV/HTLV 0.09% (N=6) and HIV/HBV/HTLV 0.07% (N=5). Conclusion: This study confirmed an overall high prevalence of HIV and HBV infections among patients receiving blood products from the SANBS. Compared to the general population, the HIV prevalence in blood recipients was two-fold higher. Patients receiving a blood transfusion from the SANBS have high rates of HIV, HBV and HTLV which should be taken into consideration when determining donor screening strategies.