The analysis of road traffic accident data in the implementation of road safety remedial programmes

Thesis (M.Ing.)--Stellenbosch University, 2001.ENGLISH ABSTRACT: A road safety remedial programme has as an objective the improvement of road transportation safety by applying road safety engineering remedial measures to hazardous road network elements in a manner that will be economically efficient. Since accident data is the primary manifestation of poor safety levels it must be analysed in manner that will support the overall objective of economic efficiency. Three steps in the process of implementing a road safety remedial programme, that rely on the systematic analysis of accident data, are the identification of hazardous locations, the ranking of hazardous locations and the evaluation of remedial measure effectiveness. The efficiency of a road safety remedial programme can be enhanced by using appropriate methodologies to measure safety, identify and rank hazardous locations and to determine the effectiveness of road safety remedial measures. There are a number of methodologies available to perform these tasks, although some perform much better than other. Methodologies based on the Empirical Bayesian approach generally provide better results than the Conventional methods. Bayesian methodologies are not often used in South Africa. To do so would require the additional training of students and engineering professionals as well as more research by tertiary and other research institutions. The efficiency of a road safety remedial programme can be compromised by using poor quality accident data. In South Africa the quality of accident data is generally poor and should more attention be given to the proper management and control of accident data. This thesis will report on, investigate and evaluate Bayesian and Conventional accident data analysis methodologies.AFRIKAANSE OPSOMMING: Die doel van 'n padveiligheidsverbeteringsprogram is om op die mees koste effektiewe manier die veiligheid van onveilige padnetwerkelemente te verbeter deur die toepassing van ingenieursmaatreëls. Aangesien padveiligheid direk verband hou met verkeersongelukke vereis die koste effektiewe implementering van 'n padveiligheidsverbeteringsprogram die doelgerigte en korrekte ontleding van ongeluksdata. Om 'n padveiligheidsverbeteringsprogram te implementeer word die ontleding van ongeluksdata verlang vir die identifisering en priortisering van gevaarkolle, sowel as om die effektiwiteit van verbeteringsmaatreëls te bepaal. Die koste effektiwiteit van 'n padveiligheidsverbeteringsprogram kan verbeter word deur die regte metodes te kies om padveiligheid te meet, gevaarkolle te identifiseer en te prioritiseer en om die effektiwiteit van verbeteringsmaatreëls te bepaal. Daar is verskeie metodes om hierdie ontledings te doen, alhoewel sommige van die metodes beter is as ander. Die 'Bayesian' metodes lewer oor die algemeen beter resultate as die gewone konvensionele metodes. 'Bayesian' metodes word nie. in Suid Afrika toegepas nie. Om dit te doen sal addisionele opleiding van studente en ingenieurs vereis, sowel as addisionele navorsing deur universiteite en ander navorsing instansies. Die gebruik van swak kwaliteit ongeluksdata kan die integriteit van 'n padveiligheidsverbeteringsprogram benadeel. Die kwaliteit van ongeluksdata in Suid Afrika is oor die algemeen swak en behoort meer aandag gegee te word aan die bestuur en kontrole van ongeluksdata. Die doel van hierdie tesis is om verslag te doen oor 'Bayesian' en konvensionele metodes wat gebruik kan word om ongeluksdata te ontleed, dit te ondersoek en te evalueer.Maste

Diagnostic accuracy of computed tomography coronary angiography in patients with a zero calcium score

To evaluate the diagnostic accuracy of 64-slice CT coronary angiography (CT-CA) for the detection of significant coronary artery stenosis in patients with zero on the Agatston Calcium Score (CACS). We enrolled 279 consecutive patients (96 male, mean age 48±12 years) with suspected coronary artery disease. Patients were symptomatic (n=208) or asymptomatic (n=71), and underwent conventional coronary angiography (CAG). For CT-CA we administered an IV bolus of 100 ml of iodinated contrast material. CT-CA was compared to CAG using a threshold for significant stenosis of ≤50%. The prevalence of disease demonstrated at CAG was 15% (1.4% in asymptomatic). The population at CAG showed no or non-significant disease in 85% (238/279), single vessel disease in 9% (25/279), and multi-vessel disease in 6% (16/279). Sensitivity, specificity, and positive and negative predictive values of CT-CA vs. CAG on the patient level were 100%, 95%, 76%, and 100% in the overall population and 100%, 100%, 100%, and 100% in asymptomatic patients, respectively. CT-CA proves high diagnostic performance in patients with or without symptoms and with zero CACS. The prevalence of significant disease detected by CT-CA was not negligible in asymptomatic patients. The role of CT-CA in asymptomatic patients remains uncertain

PIWI-interacting RNAs as novel regulators of pancreatic beta cell function.

P-element induced Wimpy testis (PIWI)-interacting RNAs (piRNAs) are small non-coding RNAs that interact with PIWI proteins and guide them to silence transposable elements. They are abundantly expressed in germline cells and play key roles in spermatogenesis. There is mounting evidence that piRNAs are also present in somatic cells, where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta cell activities. piRNA profiling of rat pancreatic islets was performed by microarray analysis. The functions of piRNAs were investigated by silencing the two main Piwi genes or by modulating the level of selected piRNAs in islet cells. We detected about 18,000 piRNAs in rat pancreatic islets, many of which were differentially expressed throughout islet postnatal development. Moreover, we identified changes in the level of several piRNAs in the islets of Goto-Kakizaki rats, a well-established animal model of type 2 diabetes. Silencing of Piwil2 or Piwil4 genes in adult rat islets caused a reduction in the level of several piRNAs and resulted in defective insulin secretion and increased resistance of the cells to cytokine-induced cell death. Furthermore, overexpression in the islets of control animals of two piRNAs that are upregulated in diabetic rats led to a selective defect in glucose-induced insulin release. Our results provide evidence for a role of PIWI proteins and their associated piRNAs in the control of beta cell functions, and suggest a possible involvement in the development of type 2 diabetes. Data have been deposited in Gene Expression Omnibus repository under the accession number GSE93792. Data can be accessed via the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ojklueugdzehpkv&acc=GSE93792

Diagnostic accuracy of 64-slice computed tomography coronary angiography for the detection of in-stent restenosis: A meta-analysis

Background: We sought to evaluate the diagnostic accuracy of 64-slice multi-detector row computed tomography (MDCT) compared with invasive coronary angiography for in-stent restenosis (ISR) detection. Methods: MEDLINE, Cochrane library, and BioMed Central database searches were performed until April 2009 for original articles. Inclusion criteria were (1) 64-MDCT was used as a diagnostic test for ISR, with >50% diameter stenosis selected as the cut-off criterion for significant ISR, using invasive coronary angiography and quantitative coronary angiography as the standard of reference; (2) absolute numbers of true positive, false positive, true negative, and false negative results could be derived. Standard meta-analytic methods were applied. Results: Nine studies with a total of 598 patients with 978 stents included were considered eligible. On average, 9% of stents were unassessable (range 0-42%). Accuracy tests with 95% confidence intervals (CIs) comparing 64-MDCT vs invasive coronary angiography showed that pooled sensitivity, specificity, positive and negative likelihood ratio (random effect model) values were: 86% (95% CI 80-91%), 93% (95% CI 91-95%), 12.32 (95% CI 7.26-20.92), 0.18 (95% CI 0.12-0.28) for binary ISR detection. The symmetric area under the curve value was 0.94, indicating good agreement between 64-MDCT and invasive coronary angiography. Conclusions: 64-MDCT has a good diagnostic accuracy for ISR detection with a particularly high negative predictive value. However, still a relatively large proportion of stents remains uninterpretable. Accordingly, only in selected patients, 64-MDCT may serve as a potential alternative noninvasive method to rule out ISR

Incorporating ‘recruitment’ in matrix projection models : estimation, parameters, and the influence of model structure

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Ornithology 152, Suppl.2 (2012):585-595, doi:10.1007/s10336-010-0573-1.Advances in the estimation of population parameters using encounter data from marked individuals have made it possible to include estimates of the probability of recruitment in population projection models. However, the projected growth rate of the population, and the sensitivity of projected growth to changes in recruitment, can vary significantly depending upon both the structural form of the model and how recruitment is parameterized. We show that the common practices of (1) collapsing some age classes into a single, terminal ‘aggregated’ age-class, and (2) parameterizing recruitment using the proportion of recruited individuals (breeders) in a given age-class may confound analysis of age-based (Leslie) matrix projection models in some instances, relative to state-based projection models where recruited and pre-recruited individuals are treated as separate states. Failing to account for these differences can lead to misinterpretation of the relative role of recruitment in the dynamics of an age-structured population.We show that such problems can be avoided, either by structural changes to the terminal aggregated age-class in age-based models, or by using using a state-based model instead. Since all the metrics of general interest from a classical age-based matrix models are readily derived from a state-based model equivalent, this suggests there may be little reason to use the classical age-based approach in situations where recruitment is a parameter of interest

Local host response following an intramammary challenge with Staphylococcus fleurettii and different strains of Staphylococcus chromogenes in dairy heifers

Coagulase-negative staphylococci (CNS) are a common cause of subclinical mastitis in dairy cattle. The CNS inhabit various ecological habitats, ranging between the environment and the host. In order to obtain a better insight into the host response, an experimental infection was carried out in eight healthy heifers in mid-lactation with three different CNS strains: a Staphylococcus fleurettii strain originating from sawdust bedding, an intramammary Staphylococcus chromogenes strain originating from a persistent intramammary infection (S. chromogenes IM) and a S. chromogenes strain isolated from a heifer's teat apex (S. chromogenes TA). Each heifer was inoculated in the mammary gland with 1.0 x 10(6) colony forming units of each bacterial strain (one strain per udder quarter), whereas the remaining quarter was infused with phosphate-buffered saline. Overall, the CNS evoked a mild local host response. The somatic cell count increased in all S. fleurettii-inoculated quarters, although the strain was eliminated within 12 h. The two S. chromogenes strains were shed in larger numbers for a longer period. Bacterial and somatic cell counts, as well as neutrophil responses, were higher after inoculation with S. chromogenes IM than with S. chromogenes TA. In conclusion, these results suggest that S. chromogenes might be better adapted to the mammary gland than S. fleurettii. Furthermore, not all S. chromogenes strains induce the same local host response

Distribution of Class 1 Integrons with IS26-Mediated Deletions in Their 3′-Conserved Segments in Escherichia coli of Human and Animal Origin

Class 1 integrons play a role in the emergence of multi-resistant bacteria by facilitating the recruitment of gene cassettes encoding antibiotic resistance genes. 512 E. coli strains sourced from humans (n = 202), animals (n = 304) and the environment (n = 6) were screened for the presence of the intI1 gene. In 31/79 integron positive E. coli strains, the gene cassette regions could not be PCR amplified using standard primers. DNA sequence analysis of 6 serologically diverse strains revealed atypical integrons harboured the dfrA5 cassette gene and only 24 bp of the integron 3′-conserved segment (CS) remained, due to the insertion of IS26. PCR targeting intI1 and IS26 followed by restriction fragment length polymorphism (RFLP) analysis identified the integron-dfrA5-IS26 element in 27 E. coli strains of bovine origin and 4 strains of human origin. Southern hybridization and transformation studies revealed the integron-dfrA5-IS26 gene arrangement was either chromosomally located or plasmid borne. Plasmid location in 4/9 E. coli strains and PCR linkage of Tn21 transposition genes with the intI1 gene in 20/31 strains, suggests this element is readily disseminated by horizontal transfer

Treatment of CoQ10 Deficient Fibroblasts with Ubiquinone, CoQ Analogs, and Vitamin C: Time- and Compound-Dependent Effects

Background: Coenzyme Q(10) (CoQ(10)) and its analogs are used therapeutically by virtue of their functions as electron carriers, antioxidant compounds, or both. However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress.Methodology/Principal Findings: To test these concepts, we have evaluated the effects of CoQ(10), coenzyme Q(2) (CoQ(2)), idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ(10) deficiency. A final concentration of 5 mu M of each compound was chosen to approximate the plasma concentration of CoQ(10) of patients treated with oral ubiquinone. CoQ(10) supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ(10) deficient fibroblasts therein normalizing the bioenergetics status of the cells. Other compounds did not affect cellular bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production and oxidative stress-induced cell death were normalized by all supplements.Conclusions/Significance: These results indicate that: 1) pharmacokinetics of CoQ(10) in reaching the mitochondrial respiratory chain is delayed; 2) short-tail ubiquinone analogs cannot replace CoQ(10) in the mitochondrial respiratory chain under conditions of CoQ(10) deficiency; and 3) oxidative stress and cell death can be counteracted by administration of lipophilic or hydrophilic antioxidants. The results of our in vitro experiments suggest that primary CoQ(10) deficiencies should be treated with CoQ(10) supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ(2). Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present

Nephronophthisis

Nephronophthisis (NPH) is an autosomal recessive disease characterized by a chronic tubulointerstitial nephritis that progress to terminal renal failure during the second decade (juvenile form) or before the age of 5 years (infantile form). In the juvenile form, a urine concentration defect starts during the first decade, and a progressive deterioration of renal function is observed in the following years. Kidney size may be normal, but loss of corticomedullary differentiation is often observed, and cysts occur usually after patients have progressed to end-stage renal failure. Histologic lesions are characterized by tubular basement membrane anomalies, tubular atrophy, and interstitial fibrosis. The infantile form is characterized by cortical microcysts and progression to end-stage renal failure before 5 years of age. Some children present with extrarenal symptoms: retinitis pigmentosa (Senior-Løken syndrome), mental retardation, cerebellar ataxia, bone anomalies, or liver fibrosis. Positional cloning and candidate gene approaches led to the identification of eight causative genes (NPHP1, 3, 4, 5, 6, 7, 8, and 9) responsible for the juvenile NPH and one gene NPHP2 for the infantile form. NPH and associated disorders are considered as ciliopathies, as all NPHP gene products are expressed in the primary cilia, similarly to the polycystic kidney disease (PKD) proteins