588 research outputs found
Financial Statements Manipulations Using Beneish Model and Probit Regression Model. A Case of Banking Sector in Kenya
The main objective of the study was to establish whether the banks in Kenya were involved in financial statement manipulations. The study involved all the banks registered and operating in Kenya and whose financial statements are published for public consumption. Beneish five-variable model was first used to categorize the banks as likely non-manipulators and likely manipulators. The probit regression model was used to determine non-manipulators and manipulators based on the averages derived from non-manipulators using Beneish five-variable model. The results obtained showed that 78.8% of all banks were not involved in financial statement manipulations while 21.2% were involved in financial statement manipulations. The study concluded that some banks that were involved in financial statement manipulations. The study recommended that both internal and control auditors should compute individual indices to determine whether the preparers of financial statements were involved in manipulations. Further it was recommended that the organizations should enhance and strengthen the ICS to seal the loopholes utilized in financial statement manipulations
Analysis for prevalence and physical linkages amongst integrons, ISEcp1, ISCR1, Tn21 and Tn7 encountered in Escherichia coli strains from hospitalized and non-hospitalized patients in Kenya during a 19-year period (1992-2011)
Background: We determined the prevalence and evidence for physical linkage amongst integrons, insertion sequences, Tn21 and Tn7 transposons in a collection of 1327 E. coli obtained over a 19-year period from patients in Kenya.
Results: The prevalence of class 1 integrons was 35%, class 2 integrons were detected in 3 isolates but no isolate contained a class 3 integron. Integron lacking the 3'-CS or those linked to sul3 gene or IS26 or those containing the ISCR1 were only detected in multidrug resistant (MDR) strains. The dfrAs were the most common cassettes and their prevalence was: -dfrA1( 28%), dfrA12( 20%), dfA17( 9%), dfrA7( 9%), and dfrA16( 5%). The aadA were the second most abundant cassettes and their prevalence was: -aadA1( 25%), aadA2( 21%), and aadA5( 14%). Other cassettes occurred in lower prevalence of below 5%. Prevalence of Tn21, ISEcp1, ISCR1 and IS26 was 22%, 10%, 15%, and 7% respectively. Majority of Tn21 containing integrons carried a complete set of transposition genes while class 2 integrons were borne on Tn7 transposon. The qnrA genes were detected in 34( 3%) isolates while 19( 1%) carried qnrB. All qnr genes were in MDR strains carrying integrons containing the ISCR1. Close to 88% of blaTEM-52 were linked to IS26 while = 80% of blaCTX-Ms and blaCMYs were linked to ISEcp1. Only a few studies have identified a blaCTX-M-9 containing an ISEcp1 element as reported in this study. Multiple genetic elements, especially those borne on incIl, incFII, and incL/M plasmids, and their associated resistance genes were transferrable en bloc to E. coli strain J53 in mating experiments.
Conclusions: This is the first detailed study on the prevalence of selected elements implicated in evolution of resistance determinants in a large collection of clinical E. coli in Africa. Proliferation of such strains carrying multiple resistance elements is likely to compromise the use of affordable and available treatment options for majority of poor patients in Africa. There is therefore a need to monitor the spread of these highly resistant strains in developing countries through proper infection control and appropriate use of antimicrobials
Technical and economic analysis of parabolic trough concentrating solar thermal power plant
Includes abstract.Includes bibliographical references.This thesis reports on the technical and economic analysis of wet and dry cooling technologies of parabolic trough CSTP plant. This was done through modelling and simulation of a standalone and grid connected parabolic trough using the System Advisor Model (SAM)
Male genital tract versus blood HIV-1 compartmentalization and selection: the first step of the transmission bottleneck?
Introduction
Sexual transmission of HIV-1 accounts for more than 80% of all the transmissions globally. After transmission, approximately 80% of the newly disseminated infections can be traced to a single variant, which comes from the minor HIV-1 population within the transmitting donor. This has led to the widely accepted idea of an HIV-1 transmission bottleneck. The nature of this bottleneck is not fully understood. Many studies working on understanding the nature of the transmitted virus have reported discordant traits of transmitted/founder viruses compared to viral isolates from chronically infected individuals. Such studies therefore lacked analysis of the intermediate step between these two populations: HIV-1 from the genital tract of the donors: where viruses are on their way to transmission to a new recipient. Importantly, numerous prior studies have shown that there is compartmentalization of HIV-1 populations between the general circulation and the genital tract, raising the possibility that the genital tract is an important selective environment. Collectively, prior studies of genital tract compartmentalization in males detected compartmentalization in about half of the donors studied, although by using techniques with limited depth of sampling than that employed in our study. The virus that establishes disseminated infection in a new recipient is selected. However, the extent to which this selection occurs before, during or after crossing the mucosal surfaces of the recipient is less clear – the period during which transmission selection could extend far back to the donor, and the donor’s genital tract. In other words, it is not clear as to what extent the transmission bottleneck occurs during compartmentalization of viral populations in the genital tract tissues. The design of an effective vaccine and other intervention strategies will rely upon the understanding the nature of the transmitted virus as this is the virus that must be targeted.
This thesis
Compartmentalization of minor variants cannot be tracked by techniques previously used to describe compartmentalization between the genital tract and the blood circulation. We therefore used deep sequencing-based techniques to further understand compartmentalization of viral populations between blood and the male genital tract. In addition, we tested the sensitivity of variants to a range of entry and other inhibitors in order to explore possible changes in function that may arise when viral variants grow in the shifted selective milieu of the genital tract. We further hypothesized that this change of selective milieu as HIV-1 moves from blood into the genital tract may lead to viral variants in semen that are sensitive to autologous neutralization because such sensitive variants may be able to grow in the genital tract, which is presumably partially or completely shielded from antibodies. Because the viral populations in semen comes from a site that may be relatively protected from antibodies, they may be permitted to evolve differently in the relative absence of antibody pressure. It is possible that evolution of the virus within the genital tract is a significant part of the change the virus undergoes on its way to establishment of a new disseminated infection in the new recipient. We considered this possibility because even some small molecules like those of some antiretroviral drugs do not penetrate the genital tract effectively under some circumstances, raising the possibility that antibodies might not always penetrate in all areas of the genital tract.
This thesis had three objectives:
1. To evaluate HIV-1 compartmentalization in blood and the male genital tract using next generation sequencing to understand the nature of viral populations in these anatomical sites in greater detail.
2. To identify the differences in sensitivity of blood and semen variants to entry inhibitors to obtain information about differences in function between HIV-1 populations in blood vs the male genital tract.
3. To compare neutralization sensitivities of viral variants compartmentalized in blood and semen by testing their sensitivity to neutralization by autologous antibodies. As a control, we measured sensitivity to a pool of clade-matched heterologous sera to determine if any observed difference was due to global changes in neutralization sensitivity.
Methods
Study participants
Forty-four HIV-1 seropositive men were recruited and then requested to donate blood and semen samples at ANOVA Health’s Ivan Toms clinics at Woodstock and Green Point or through their mobile clinic in Khayelitsha, all in Cape Town, South Africa. Viral loads from blood and semen and CD4+ T cell counts from blood were measured. HIV-1 was enriched from semen using a Nycodenz gradient, and then concentrated using ultracentrifugation.
Chapter 2: HIV-1 Compartmentalization in blood and semen
Next generation sequencing on Illumina paired-end Miseq platform was performed. To our knowledge there is no published study that has used this technique to study male genital tract HIV-1 variants in chronically infected male donors, although there is one that does so for acutely infected donors. We argue here that this is a superior method of sampling populations in blood and the male genital tract. In particular, it allowed us to more accurately track minor populations within each compartment. Additionally, the use of PrimerID approach allowed us to more clearly identify clonal amplification events in the HIV-1 populations. Sequencing was performed on either the V3 or C3-V5 region of the HIV-1 envelope gene from paired blood and semen samples from 11 donors. To evaluate compartmentalization, populations from blood and semen were compared using three standard techniques, Slatkin Maddison Test (SMT), Wrights measure of population subdivision (FST) and nearest neighbour statistic (Snn). Clonal amplification and results of modelling a lower depth of sampling are also presented.
Chapter 3: Sensitivity of blood and semen variants to entry inhibitors and changes in function
From three subjects who exhibited the highest extent of compartmentalization, full-length envelope clones derived from semen and blood RNA were made using limiting dilution PCR (single genome amplification), which provided the advantage of minimizing PCR-based artificial recombination. A high fidelity Taq polymerase was also used to minimize base-substitution errors. An average of 10 clones were isolated per compartment. Pseudoviruses were then constructed from the full-length envelope clones from blood and semen. The sensitivities of these pseudoviruses were tested against HIV-1 entry inhibitors; Maraviroc, PSCRANTES, enfurvirtide (T-20) and JM2987. Maraviroc and PSC-RANTES are CCR5 inhibitors while JM2987 is a CXCR4 inhibitor. Enfurvirtide (T-20) is a fusion inhibitor blocking the virus from entering cells. The full-length clones used to make the pseudoviruses were also sequenced and genomic variations in variable loop characteristics (length and number of potential glycosylation sites) between blood and semen compared.
Chapter 4: Sensitivity of blood and semen variants to autologous and heterologous antibodies
To study the differences in sensitivity of blood and semen variants to antibodies, pseudoviruses cloned from semen RNA and blood RNA (above) were tested for their sensitivities to donor antibodies collected at the same time the samples were collected or to a pool of HIV-1 subtype C sera.
Results
Objective 1: Viral compartmentalization via next generation sequencing
HIV-1 populations were compartmentalized in all the 11 donors studied but to varying extents. Donor SVB043 had the most compartmentalized viral populations between blood and the male genital compartment using all the three measures of compartmentalization. Further analysis of the phylogenetic trees revealed that some clusters contained either purely blood or semen sequences, even in trees generated from analysis of donors with weakest compartmentalization. This might explain the viral compartmentalization signal in these weakly compartmentalized donors. To mimic reduced sampling depth, subsampling of the Illumina Miseq data with a small number of sequences was done. This analysis revealed that viral compartmentalization between blood and male genital tract would likely (>50% estimated likelihood) have been detected in only 5/11 (45%) of the donors, a proportion which is very similar to the aggregate proportion from previous studies that had used single genome amplification (SGA) analysis. This means that the difference in detecting HIV-1 compartmentalization in this thesis vs previous studies can be explained by the depth of sequencing achieved here and that there is no evidence that the dynamics of the viral populations studied in this thesis were different from those previously studied. In addition, the most recent common ancestor of semen variants was mostly located in blood, indicating the male genital tract was seeded by incoming variants from blood. Clonal amplification was also observed in all the 11 study participants and it was a characteristic of variants from blood and the male genital tract and its frequency did not obviously correlate with the severity of compartmentalization. In sum, blood and male genital tract HIV-1 compartmentalization and clonal amplification is present in most or all HIV-1 infected males but was not detected in all individuals in previous studies when using techniques with lower depth of sampling.
Objective 2: Sensitivities of blood and semen variants to entry inhibitors and variable loop characteristics
Viral variants from the most compartmentalized donors had variations in sensitivities to entry inhibitors; although the direction of the difference was inconsistent. Donor SVB043 who had the most severely compartmentalized viral populations between blood and semen, had semen viruses that were 1.67 (95%CI 1.08 – 2.56) times more resistant to maraviroc (p=0.024) while SVB008 which was the second most compartmentalized donor, had semen isolates that were 4.8 (95%CI 2.76 – 8.28) times more sensitive to inhibition by maraviroc (p < 0.0001). The meaning of this discrepancy is not entirely clear. It could mean that trait(s) that are selected for in genital tract variants over blood circulation variants are linked to the CCR5 binding region, and that the linked CCR5 genotype was carried along with the selected trait(s). There were no differences in sensitivity to maraviroc between blood and semen clones for donor SVB049 (p=0.847); although this donor on further investigation was found to have functional levels of efavirenz in his blood (3µg/ml, which were within the therapeutic range of 1-4µg/ml) indicating that he was likely on antiretroviral therapy (ART). This was not known to the clinic staff at the clinic at which he was known to receive care and was recruited to this study. The direction of sensitivities to PSC_RANTES (another CCR5 inhibitor) was concordant to that observed for maraviroc for donors SVB008 and SVB049 but not for donor SVB043 where semen variants were 1.67 (95%CI 1.08 – 2.56) times less sensitive than blood variants to maraviroc, with no detected difference in sensitivity to PSC_RANTES (p = 0.783). This discrepancy for donor SVB043 probably reflects the difference in mode of action between Maraviroc and PSC_RANTES. The change in envelope conformation over movement from blood into the genital tract presumably affected the maraviroc binding site and not PSC_RANTES. All the clones from blood and semen for the three most viral compartmentalized donors were resistant to CXCR4 inhibitor suggesting that they were all R5 tropic viruses. There were no differences in sensitivities of blood and semen viruses to fusion inhibitor T-20. The findings here suggest a changed viral envelope conformation/structure for the viruses in the male genital tract. The discordance suggests that the selected trait over movement of virus from blood into genital tract is linked or close to CCR5 binding site but itself does not involve binding to CCR5 coreceptor. Differences in length and number of glycosylation sites were found between variants from blood and those from the genital tract but the direction of the difference was also inconsistent. Donor SVB043 who had the most compartmentalized blood and seminal variants had semen variants that had longer and more glycosylated envelopes. Donor SVB008 who had the second most compartmentalized blood and semen variants had no difference in variable loop length, but semen variants were less glycosylated. This therefore shows that selection for some of the previous reported traits of acute viral isolates may have started in the genital tract in a subset of the donors.
Objective 3: Sensitivities of blood and semen variants to autologous and heterologous antibodies
Viral populations compartmentalized in blood and the male genital compartment displayed a range of sensitivities to autologous and heterologous neutralization. Donor SVB043 who had the most compartmentalized viral populations between blood and the genital tract; had semen clones that were 1.75 (95%CI 1.11-2.78) times more sensitive to autologous neutralization compared to blood clones (p = 0.018). In contrast, donors SVB008 and SVB049 who exhibited substantial compartmentalization, but to a lesser extent than that found in donor SVB043, showed no differences in sensitivities of blood and semen variants to autologous serum. Neutralization sensitivity to a pool of heterologous subtypematched sera revealed no differences in sensitivities between clones from blood and semen for donors SVB043 and SVB008. Interpretation of results from donor SVB049 are clouded by the donor’s ART use. Overall, these results suggest that, in some individuals, a shift in selective milieu of the genital tract virus occurs. This is presumably due to partial or complete shielding of the genital tract tissue from circulating antibodies, and this shielding shape the populations of HIV-1 variants available for transmission from some but not all individuals.
Overall conclusions
Our data add to the existing knowledge of existence of distinct viral populations between blood and the male genital tract of chronically HIV-1 infected donors. Importantly, and for the first time, we present evidence that HIV-1 compartmentalization between blood and the male genital tract is present in most or all donors, and that some clones are severely compartmentalized even in donors who exhibit very mild compartmentalization. It appears that viral compartmentalization and clonal amplification in these anatomical sites may be present in most individuals but remained undetected in some individuals in previous studies due to the lower depth of sampling applied. We observed a discordance in entry inhibitor sensitivities and variable loop characteristics between blood vs semen variants among different donors. This may suggest a changed envelope conformation over importation of virus from blood into the genital tract. This change seems to be near or linked to the co-receptor binding site but does not appear to directly involve the co-receptor binding tested in this thesis. This interpretation also may explain the discordance in viral characteristics for the virus establishing infection reported in other studies. This thesis also shows that some of these traits of the transmitted/founder virus relating to neutralization sensitivity, sensitivity to entry inhibitors and variable loop characteristics may originate in and/or be enhanced by transition through the genital tract on the way to becoming a founder virus. These results are important in understanding how the populations in the genital compartment are selected, giving rise to the population of HIV-1 that is available for transmission to a new individual. An understanding of the dynamics of HIV-1 populations prior to and during transmission is important for vaccine design and other intervention strategies
Factors Determining Adoption of New Agricultural Technology by Smallholder Farmers in Developing Countries
Agricultural technologies are seen as an important route out of poverty in most of the developing countries. However the rate of adoption of these technologies has remained low in most of these countries. This study aim at shedding some light on the potential factors that influence agricultural technology adoption in developing countries. It does so by reviewing previous studies done on technology adoption. From the study technological, economic, institutional factors and human specific factors are found to be the determinants of agricultural technology adoption. The study recommend the future studies on adoption to widen the range of variables used by including perception of farmers towards new technology. Keywords: Technology, Adoption, smallholde
Predictability of GARCH-Type Models in Estimating Stock Returns Volatility. Evidence from Kenya
Purpose: The aim of this paper was to  evaluate which of the seven GARCH-type models, namely sGARCH, IGARCH, EGARCH, TGARCH, GJRGARCH, APARCH, and CGARCH, was suitable for predicting the Nairobi Securities Exchange-listed firms' volatility.
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Theoritical framework: The Efficient Market Hypothesis is crucial in predicting market value of stocks. Therefore, this study employed the efficient market hypothesis to the the predictability of the stocks returns volatility.
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Design/Methodology/Approach: In this study, we used census approach to collect data from 49 Nairobi Securities Exchange listed firms. The data was collected from 1st January 2011 to 31st December 2020. TO evaluate the volatility, we used the GARCH-type models.
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Findings: The study found that the APARCH model as the best suitable for forecasting the volatility of Nairobi Securities Exchange-listed firms.
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Research, Practical & Social implications: We propose the the APARCH model as the best suitable model for predicting volatility of stock returns. The findings can be used by investors in making judicious financial decisions. For acedmic purpose, the findings are essential in supporting new knowledge of which model is best fit in predicting the NSE stocks returns volatility.
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Original/ Value: The study contributes to the literature on the best suitable model in predicting the volatility of the stocks returns
From dispossession to disappointment: neo- liberalism and South African land reform policy
Paper presented at the Wits History Workshop: Forging the links between historical research and the policy process, 18-19 September 1999.Land ownership in South Africa is inequitable and characterised by exploitative social relations. The land policy process represents the triumph of the dominant powerful groups, mainly the landowning classes. The concerns of ordinary rural people have been marginalised. The paper examines the processes that lead to the ANC's land reform policy
Characterisation of community acquired non-typhoidal Salmonella from bacteraemia and diarrhoeal infections in children admitted to hospital in Nairobi, Kenya
BACKGROUND: In sub-Saharan Africa community-acquired non-typhoidal Salmonella (NTS) is a major cause of high morbidity and death among children under 5 years of age especially from resource poor settings. The emergence of multidrug resistance is a major challenge in treatment of life threatening invasive NTS infections in these settings. RESULTS: Overall 170 (51.2%) of children presented with bacteraemia alone, 28 (8.4%) with gastroenteritis and bacteraemia and 134 (40.4%) with gastroenteritis alone. NTS serotypes obtained from all the cases included S. Typhimurium (196; 59%), S. Enteritidis (94; 28.3%) and other serotypes in smaller numbers (42; 12.7%); distribution of these serotypes among cases with bacteremia or gastroenteritis was not significantly different. A significantly higher proportion of younger children (< 3 years of age) and those from the slums presented with invasive NTS compared to older children and those from upper socio-economic groups (p < 0.001). One hundred and forty-seven (44.3%) NTS were resistant to 3 or more antibiotics, and out of these 59% were resistant to ampicillin, chloramphenicol and tetracycline. There was no significant difference in antibiotic resistance between the two serotypes, S. Typhimurium and S. Enteritidis. Ceftriaxone and ciprofloxacin were the only antibiotics tested to which all the NTS were fully susceptible. Using Pulsed Field Gel Electrophoresis (PFGE) there were 3 main patterns of S. Typhimurium and 2 main patterns of S. Enteritidis among cases of bacteraemia and gastroenteritis. CONCLUSION: Serotype distribution, antibiotic susceptibility and PFGE patterns of NTS causing bacteraemia and gastroenteritis did not differ significantly. The high prevalence of NTS strains resistant to most of the commonly used antimicrobials is of major public health concern
Epidemiology and Antimicrobial Resistance Patterns in Enteric Fever among patients in Garissa County, a Semi-Arid Region of North Eastern Kenya
Typhoid and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in developing countries where enteric fever is associated with poor sanitation and unsafe food and water. Quantification of disease burden is crucial for policy making about the deployment of enteric fever prevention measures and vaccines. This cross-sectional study was undertaken to determine the epidemiology and antimicrobial resistance pattern in bacterial aetiologies of enteric fever among patients attending Garissa County Referral Hospital, (GCRH) located in a semi-arid region of North Eastern Kenya. Blood and stool samples were obtained from 379 consenting patients and a detailed sociodemographic questionnaire was administered. Isolation and identification of Salmonella Typhi, S. Paratyphi A and S. Paratyphi B were obtained by convectional culture, PCR and Vitek-2 compact detection method. Antimicrobial susceptibility testing was done using Kirby-Bauer’s disc diffusion method. Multidrug resistance was defined as co-resistance to ampicillin, chloramphenicol and co- trimoxazole. Eight of the 379 (2.1%) participants were positive for Salmonella spp. Of the 8 Salmonella isolates were S. Typhi (n=2; 25%), S. Paratyphi A (n=2; 25%) and S. Paratyphi B (n=4; 50%). Resistance to ampicillin, tetracycline, gentamycin, chloramphenicol, nalidixic acid and trimethoprim-sulfamethoxazole was 100%, 87.5%, 75%, 50%, 25% and 25% respectively. No isolate showed resistance to ciprofloxacin. Half of all S. typhi, S. paratyphi A and B were multidrug-resistant. Risk factors including water and food (such as often eating outside homestead, family eating from a common plate, taking locally prepared cold drinks, family wash hands in common basin), low socio-economic status and availability of a previous laboratory confirmation of typhoid fever were associated with S. Typhi and S. Paratyphi infection. The isolation of a large proportion of MDR S. Typhi, S. Paratyphi A and B is worrying. Although these isolates were susceptible to fluoroquinolones, there is need for routine surveillance to monitor susceptibility to the initial first line antibiotics in clinical settings since the MDR strains have lately shown increased resistance. Addressing issues of contaminated food, water, sanitation and hygiene and low socio-economic status is likely to prevent and reduce the burden on enteric fever in this region. Keywords: Enteric Fever, Molecular Epidemiology, Antimicrobial Resistance Pattern, Semi-Arid Region of North Eastern Kenya DOI: 10.7176/JHMN/60-14 Publication date:March 31st 201
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