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    Oxidative stress Zambia

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    An assessment of gastric cancer associated factors and strategies for early case detection in patients seen at the university teaching hospital in Lusaka, Zambia

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    ThesisABSTRACT Gastric cancer is one of the leading causes of cancer related mortality globally. It carries a very poor prognosis with a one-year survival rate of less than 15%. The main objective of this study was to investigate environmental, biological and dietary factors associated with gastric cancer, and to explore the potential of using blood in gastric juice for detection of gastric mucosal lesions through pre-endoscopy screening. The study was conducted at the University Teaching Hospital, in Lusaka, Zambia. It was a case-control study of patients with histologically confirmed gastric adenocarcinoma (GA) or gastric premalignant (GP) lesions as cases, and those without either as controls. Questionnaires were used to collect data on basic characteristics and associated risk factors. Biological characteristics were measured in gastric juice, blood, urine, and gastric biopsies. This was done using enzyme-linked immunosorbent assay, high-performance liquid chromatography, immunofluorescence, in situ hybridisation, urine and pH test strips. A multiplex serological assay was used to quantify antibodies to thirteen immunogenic Helicobacter pylori proteins. Study data were analysed in STATA version 15 (College Station, TX, USA). Graphs were prepared in both STATA and Graphpad prism version 7. Included for analysis in this study were 388 patients, 92 (24%) of whom had gastric tumours seen during endoscopy. Results showed that gastric cancer had similar occurrence in both sexes (OR 1.1; 95% CI 0.5-1.9), and 18/92 (20%) of them were below the age of 45 years. GA disproportionately affected rural (OR 2.9; 95% CI 1.5-5.3) and poor (OR 4.2; 95% CI 1.9-9.1) people. The proportion of Epstein-Barr virus (EBV) associated GA was 11% by in situ hybridisation, and it was similar between HIV infected and uninfected patients (OR 1.5; 95% CI 0.02-22). Evidence of microsatellite instability using immunofluorescence for MutL homolog 1 was observed in 63% of GA. Patients regularly exposed to biomass smoke were more likely to have GA, (p=0.001) and to exhibit evidence of oxidative stress to DNA, (p=0.03). The odds of GA in patients with history of regular consumption of processed meat was 7.0; 95% CI 1.4-34. In patients taking green vegetables daily, the odds were 0.2; 95% CI 0.1-0.5. The median estimated 24-hour sodium excretion of 19 g (IQR 14-24 g) by the Tanaka method. Aflatoxin M1 was present in the urine of 61% of the patients, with a median; 18 ng/mg creatinine (IQR 1.7- 40) ng/mg creatinine, while 96% had ochratoxin A in their blood median; 0.1 ng/ml (IQR 0.2-0.6 ng/ml). Being Helicobacter pylori (H. pylori) seropositive (determined by the presence of at least four antibodies) was not associated with either GA (OR 1.1; 95% CI 0.5-3.3) or GP (OR 1.9; 95% CI 0.4-17.6). Antibodies to CagA (p=0.0007), VacA (p=0.0006), HcpC (p=0.0006) and Omp (p=0.03) were significantly higher in active gastric inflammation than in GA. Overall, there was no association between H. bilis or H. hepaticus seropositivity and GA or GP. Serological response to four EBV antigens was not associated with GA. The presence of blood in gastric juice was associated with gastric cancer (OR 6.7; 95% CI 2-35), with a case detection sensitivity of 91% and a specificity of 41% and an area under the receiver operating characteristic curve of 0.8; 95% CI 0.7-0.9. There was a high proportion of early onset and microsatellite unstable GA, disproportionately affecting poor rural residents. Of the infectious risk factors evaluated, H. pylori was only associated with active gastric inflammation, but not GA or GP. EBV was absent in most of the tumours and HIV showed no influence on gastric carcinogenesis. Environmental and dietary risk factors showed greater influence on GA than the infectious agents. Testing for blood in gastric juice had high sensitivity but low specificity for gastric cancer detection. Data from this thesis can be used to further analyse specific risk factors for each gastric cancer subtype and explore the pathophysiological mechanisms involved. Key words: gastric cancer, gastric premalignant lesions, risk factors, biomass smoke, mycotoxins, gastric juice

    An assessment of gastric cancer associated factors and strategies for early case detection in patients seen at the university teaching hospital in Lusaka, Zambia.

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    ThesisABSTRACT Gastric cancer is one of the leading causes of cancer related mortality globally. It carries a very poor prognosis with a one-year survival rate of less than 15%. The main objective of this study was to investigate environmental, biological and dietary factors associated with gastric cancer, and to explore the potential of using blood in gastric juice for detection of gastric mucosal lesions through pre-endoscopy screening. The study was conducted at the University Teaching Hospital, in Lusaka, Zambia. It was a case-control study of patients with histologically confirmed gastric adenocarcinoma (GA) or gastric premalignant (GP) lesions as cases, and those without either as controls. Questionnaires were used to collect data on basic characteristics and associated risk factors. Biological characteristics were measured in gastric juice, blood, urine, and gastric biopsies. This was done using enzyme-linked immunosorbent assay, high-performance liquid chromatography, immunofluorescence, in situ hybridisation, urine and pH test strips. A multiplex serological assay was used to quantify antibodies to thirteen immunogenic Helicobacter pylori proteins. Study data were analysed in STATA version 15 (College Station, TX, USA). Graphs were prepared in both STATA and Graphpad prism version 7. Included for analysis in this study were 388 patients, 92 (24%) of whom had gastric tumours seen during endoscopy. Results showed that gastric cancer had similar occurrence in both sexes (OR 1.1; 95% CI 0.5-1.9), and 18/92 (20%) of them were below the age of 45 years. GA disproportionately affected rural (OR 2.9; 95% CI 1.5-5.3) and poor (OR 4.2; 95% CI 1.9-9.1) people. The proportion of Epstein-Barr virus (EBV) associated GA was 11% by in situ hybridisation, and it was similar between HIV infected and uninfected patients (OR 1.5; 95% CI 0.02-22). Evidence of microsatellite instability using immunofluorescence for MutL homolog 1 was observed in 63% of GA. Patients regularly exposed to biomass smoke were more likely to have GA, (p=0.001) and to exhibit evidence of oxidative stress to DNA, (p=0.03). The odds of GA in patients with history of regular consumption of processed meat was 7.0; 95% CI 1.4-34. In patients taking green vegetables daily, the odds were 0.2; 95% CI 0.1-0.5. The median estimated 24-hour sodium excretion of 19 g (IQR 14-24 g) by the Tanaka method. Aflatoxin M1 was present in the urine of 61% of the patients, with a median; 18 ng/mg creatinine (IQR 1.7- 40) ng/mg creatinine, while 96% had ochratoxin A in their blood median; 0.1 ng/ml (IQR 0.2-0.6 ng/ml). Being Helicobacter pylori (H. pylori) seropositive (determined by the presence of at least four antibodies) was not associated with either GA (OR 1.1; 95% CI 0.5-3.3) or GP (OR 1.9; 95% CI 0.4-17.6). Antibodies to CagA (p=0.0007), VacA (p=0.0006), HcpC (p=0.0006) and Omp (p=0.03) were significantly higher in active gastric inflammation than in GA. Overall, there was no association between H. bilis or H. hepaticus seropositivity and GA or GP. Serological response to four EBV antigens was not associated with GA. The presence of blood in gastric juice was associated with gastric cancer (OR 6.7; 95% CI 2-35), with a case detection sensitivity of 91% and a specificity of 41% and an area under the receiver operating characteristic curve of 0.8; 95% CI 0.7-0.9. There was a high proportion of early onset and microsatellite unstable GA, disproportionately affecting poor rural residents. Of the infectious risk factors evaluated, H. pylori was only associated with active gastric inflammation, but not GA or GP. EBV was absent in most of the tumours and HIV showed no influence on gastric carcinogenesis. Environmental and dietary risk factors showed greater influence on GA than the infectious agents. Testing for blood in gastric juice had high sensitivity but low specificity for gastric cancer detection. Data from this thesis can be used to further analyse specific risk factors for each gastric cancer subtype and explore the pathophysiological mechanisms involved. Key words: gastric cancer, gastric premalignant lesions, risk factors, biomass smoke, mycotoxins, gastric juice

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Association between HIV infection and Gastric Cancer in an African Population

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    Introduction There is a shortage of systematically collected data on gastric cancer in Zambia. An audit carried out as preliminary work showed that there was a change in the epidemiology of gastric cancer since the early 1980s, and it was hypothesised that this change was linked to HIV infection. The aim of this study was to evaluate a possible association between gastric cancer and HIV infection in patients seen at the University Teaching Hospital (UTH), Lusaka. Other well known risk factors such as infection with Helicobacter pylori (H. pylori), presence of CagA, serum pepsinogen 1 to 2 ratios, smoking, alcohol intake and low income were also evaluated. Methods This was a prospective case-control study conducted over one year. Cases were patients with gastric adenocarcinoma confirmed by histopathology while controls were patients with no visible mucosal abnormality in the upper gastrointestinal tract. Two controls were enrolled for each case after matching for age and sex. The presence of HIV infection was determined by testing for HIV antibodies in each group and odds ratios (OR) was calculated to determine the presence of any association. The presence of antibodies to H.pylori, the virulence factor CagA and serum pepsinogen 1 and 2 levels were determined using ELISA. Also collected was data on other life style risk factors using an interviewer administered questionnaire. Results were analysed using STATA 10. Results A total of 38 cases and 76 controls were enrolled. There was no association between gastric cancer and HIV infection (OR 1.4, 95%CI 0.3-6.4; P=0.73). Smoking and alcohol were found to increase the odds of developing gastric cancer in both univariate and multivariate analysis (multivariate P=0.04 and P=0.02 respectively). Overall, 81% of the patients were found to be positive for H. pylori infection, with no significant difference between the cases and the controls (P=0.24). The presence of antibodies to CagA was also not different between the two groups (P=0.79). A small proportion of cases and controls had low serum levels of pepsinogen 1, (11% and 6% respectively) but this was not significantly different (P=0.45). vii However, the presence of a low pepsinogen 1 to 2 ratio was more discriminating, with a higher proportion among the cases (P=0.009). Conclusions No association was found between HIV infection and gastric cancer in the patients seen at the endoscopy unit, UTH, Lusaka. Alcohol and smoking were shown to increase the odds of developing gastric cancer. Patients with gastric cancer have a lower ratio of pepsinogen 1 to 2, although there was no significant difference in the levels of pepsinogen 1, H.pylori infection or CagA between gastric cancer patients and healthy controls. In conclusion, the reason for the apparent change in epidemiology of gastric cancer has not been established and therefore, more work still needs to be done to answer this questio

    Association between HIV Infection and Gastric Cancer in an African Population

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    Introduction There is a shortage of systematically collected data on gastric cancer in Zambia. An audit carried out as preliminary work showed that there was a change in the epidemiology of gastric cancer since the early 1980s, and it was hypothesised that this change was linked to HIV infection. The aim of this study was to evaluate a possible association between gastric cancer and HIV infection in patients seen at the University Teaching Hospital (UTH), Lusaka. Other well known risk factors such as infection with Helicobacter pylori (H. pylori), presence of CagA, serum pepsinogen 1 to 2 ratios, smoking, alcohol intake and low income were also evaluated. Methods This was a prospective case-control study conducted over one year. Cases were patients with gastric adenocarcinoma confirmed by histopathology while controls were patients with no visible mucosal abnormality in the upper gastrointestinal tract. Two controls were enrolled for each case after matching for age and sex. The presence of HIV infection was determined by testing for HIV antibodies in each group and odds ratios (OR) was calculated to determine the presence of any association. The presence of antibodies to H.pylori, the virulence factor CagA and serum pepsinogen 1 and 2 levels were determined using ELISA. Also collected was data on other life style risk factors using an interviewer administered questionnaire. Results were analysed using STATA 10. Results A total of 38 cases and 76 controls were enrolled. There was no association between gastric cancer and HIV infection (OR 1.4, 95%CI 0.3-6.4; P=0.73). Smoking and alcohol were found to increase the odds of developing gastric cancer in both univariate and multivariate analysis (multivariate P=0.04 and P=0.02 respectively). Overall, 81% of the patients were found to be positive for H. pylori infection, with no significant difference between the cases and the controls (P=0.24). The presence of antibodies to CagA was also not different between the two groups (P=0.79). A small proportion of cases and controls had low serum levels of pepsinogen 1, (11% and 6% respectively) but this was not significantly different (P=0.45).Introduction There is a shortage of systematically collected data on gastric cancer in Zambia. An audit carried out as preliminary work showed that there was a change in the epidemiology of gastric cancer since the early 1980s, and it was hypothesised that this change was linked to HIV infection. The aim of this study was to evaluate a possible association between gastric cancer and HIV infection in patients seen at the University Teaching Hospital (UTH), Lusaka. Other well known risk factors such as infection with Helicobacter pylori (H. pylori), presence of CagA, serum pepsinogen 1 to 2 ratios, smoking, alcohol intake and low income were also evaluated. Methods This was a prospective case-control study conducted over one year. Cases were patients with gastric adenocarcinoma confirmed by histopathology while controls were patients with no visible mucosal abnormality in the upper gastrointestinal tract. Two controls were enrolled for each case after matching for age and sex. The presence of HIV infection was determined by testing for HIV antibodies in each group and odds ratios (OR) was calculated to determine the presence of any association. The presence of antibodies to H.pylori, the virulence factor CagA and serum pepsinogen 1 and 2 levels were determined using ELISA. Also collected was data on other life style risk factors using an interviewer administered questionnaire. Results were analysed using STATA 10. Results A total of 38 cases and 76 controls were enrolled. There was no association between gastric cancer and HIV infection (OR 1.4, 95%CI 0.3-6.4; P=0.73). Smoking and alcohol were found to increase the odds of developing gastric cancer in both univariate and multivariate analysis (multivariate P=0.04 and P=0.02 respectively). Overall, 81% of the patients were found to be positive for H. pylori infection, with no significant difference between the cases and the controls (P=0.24). The presence of antibodies to CagA was also not different between the two groups (P=0.79). A small proportion of cases and controls had low serum levels of pepsinogen 1, (11% and 6% respectively) but this was not significantly different (P=0.45).However, the presence of a low pepsinogen 1 to 2 ratio was more discriminating, with a higher proportion among the cases (P=0.009). Conclusions No association was found between HIV infection and gastric cancer in the patients seen at the endoscopy unit, UTH, Lusaka. Alcohol and smoking were shown to increase the odds of developing gastric cancer. Patients with gastric cancer have a lower ratio of pepsinogen 1 to 2, although there was no significant difference in the levels of pepsinogen 1, H.pylori infection or CagA between gastric cancer patients and healthy controls. In conclusion, the reason for the apparent change in epidemiology of gastric cancer has not been established and therefore, more work still needs to be done to answer this question

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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