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Class of 2009 Abstract / OBJECTIVES: To determine the likelihood of pharmacists in England of reporting adverse drug reactions (ADR), whether they are aware of the reporting processes, and what they believe the reasons for not reporting may be. METHODS: A survey containing five different scenarios of ADRs was distributed to licensed, community pharmacists around Surrey, England. The responses were analyzed using rates and chi-square. RESULTS: A total of 47 surveys were returned to the researcher. Of those, 72% of the participants were likely to report the adverse drug reaction in the scenarios provided. In addition, 87.5% of the pharmacists were familiar with the reporting procedures in place in the United Kingdom. A total of 51.9% were not able to distinguish between a major and minor adverse reaction. Finally, with a X2 value of 0.070, there was not a significant difference between males and females and the likelihood of reporting these errors (p=0.79). Similarly, there was no significant difference between the likelihood of reporting an event involving a pediatric patient vs. an adult patient with a X2 value of 0.275 (p=0.599). CONCLUSIONS: Most pharmacists were aware of the procedures involved in reporting ADRs in the United Kingdom and were likely to report these ADRs. Additionally, the most common reason predicted for not reporting was due to the lack of time pharmacists have to report these events. Regardless of gender, male and female pharmacists were equally likely to report ADRs.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Master of Science in Medicine / Fetal Alcohol Syndrome (F AS), the most severe form of Fetal Alcohol Spectrum Disorder (F ASD), has traditionally been associated with maternal alcohol consumption during pregnancy. However, a number of animal studies have shown an association between paternal preconception alcohol consumption and developmental abnormalities in the offspring that resemble the features of F AS. Dysregulation of epigenetic factors (such as DNA methylation) in the presence of alcohol may provide a plausible mechanism by which paternal alcohol consumption could result in offspring affected with features of F AS. Imprinted genes are expressed in a parentof- origin manner due to DNA methylation at distinct differentially methylated regions (DMRs) and are essential for normal embryonic development. There are only two known paternally methylated DMRs in humans, with an additional one described in mice - associated with Rasgrfl. The first aim of this study was to determine whether the human RASGRFl gene contains a DMR and whether this DMR is paternally methylated. In order to assess the imprint status of RASGRF 1, a number of computational assessments were done to identify key features of imprinted loci. Pyrosequencing analysis was used to assess the methylation status of various CpO islands surrounding RASGRFi in peripheral blood and sperm DNA samples. The RASGRF i-associated CpO regions were not found to exhibit differential methylation in a parent-of-origin manner. The second aIm of the study was to examine the effect of paternal alcohol consumption on the methylation status of the IG-DMR locus in male gametes and to detennine whether alcohol is correlated with methylation in a dose-dependant manner. Methylation assessment was done using the quantitative pyrosequencing technology. While an overall reduction in methylation was noted in males who consumed alcohol after adjusting for confounding variables, the amount of alcohol consumed did not correlate with overall methylation. When analyzed by individual CpG sites, alcohol consumption was found to correlate preferentially with demethylation at CpG 3 while alcohol-dosage preferentially correlated with demethylation at CpG 7. Age was significantly correlated with an increase in the overall methylation at JG-DMR and at individual sites within JG-DMR. In conclusion, these findings support the hypothesis that paternal preconception alcohol consumption can lead to hypomethylation of nonnally hypennethylated DMRs of specific imprinted genes in human spenn. This in tum could have significant implications with regard to the regulation of developmentally significant genes in the zygote and fetus, resulting in developmental, behavioral and neurocognitive disorders.

INTRODUCTION According to ILO (2000), in developing countries about 59 per cent of labour force belongs to the agriculture sector. This is a particularly serious concern from the viewpoint of promoting the health of a population and reduction of social vulnerability in a country like Mozambique where more than half of the population depends on agriculture as their means of survival and wage earning. The current study attempts to address the agriculture mineral dust as occupational hygiene and health risk factors among agriculture workers, taking into account that dust that is breathed in may contain quartz, known as a carcinogenic and pathogenic agent. OBJECTIVE OF THE STUDY The study aims to pinpoint risk potential to health that may be caused by mineral dust through assessing occupational exposure doses to respirable dust and quartz during plowing, and primary and secondary tilling operations identified in the study, as the major dust risk operations; and the more prevailing operations in maize and root plant on medium sized farms‟ production cycle. MATERIALS AND METHODS Sampling of dust was conducted on 2 medium sized farms selected by convenience in the district of Boane (study setting) based on geological map soil characterisation of the study area. Full-time period dust samples were collected from 4 different tractor operators. The tractor operators were identified as the risky group. In total were taken seventy valid samples; thirty-nine from maize and thirty-one from root plant. Three tractor operators were fully engaged in maize cultivation and 1 was engaged in root plant during the period of the study data collection. In all occasions, the „open-cabbed‟ tractor machines were observed and used by tractor operators. The involved sampling subjects‟ operators were informed in advance about the study purpose and they accepted participation in the research. Nineteen dust samples were randomly selected for determination of the quartz fraction using the MDHS 101 Infrared Spectrophotometer Method. Active dust sampling MDHS 14/3 HD-cyclone method was applied with GLA 5000 filter type. All quality control procedures applied in active dust sampling method and gravimetric determination of concentration were checked in order to accept or reject samples for further analysis and determination of exposure concentration. RESULTS Standard statistical procedures and sampling strategy data analysis and interpretation procedures, including the SPSS software version 11.5 were used to produce valid results and findings. In the specific case of the agriculture sector, workers are found in changeable conditions and working time, therefore the effective working time distribution was estimated varying at a level of 311.6 min., 95 per cent CI (294-329.7). The observed minimal and maximal values were 179 and 500 min., respectively. The filter medium potential contamination was checked out through determination of the mass variation of the blank samples. The filter contamination was assumed possible through absorption and/or adsorption of humidity at level of minus 0.00407 mg with lower limit of minus 0.01 and upper limit of 0.00183 mg. The results on exposure indicate high exposure dose in maize crop cultivation in contrast to root plant crop cultivation. The findings show that in medium-sized farming, the average exposure to respirable dust is 0.702 (SD 0.571) and the average exposure for respirable quartz is 0.074 (SD 0.06). About 96 per cent of respirable dust exposure measurements were found in compliance with the South Africa standard for respirable dust; and for respirable quartz 74 per cent, 45 per cent and 17 per cent of exposure measurements were in compliance with the SA, NIOSH and ACGIH occupational exposure limits respectively. Each tractor operator‟s measurements showed a significant variation of the exposure concentration, probably due to the intraday and interday variation. The exposure measurements geometric standard deviation (GSD) was found equal or above 2.0 for both maize and root plant measurements and this indicates the influence of environmental factors in the exposure profile variation. CONCLUSION The research is supportive of some international published studies in which respirable quartz exposure in agriculture sector, although highly variable, has potential significance for over-exposure. The measurements of exposure to respirable quartz have shown over-exposure scenarios. However some were found below the permitted exposure limits.

Thesis (Ph.D.)--University of the Witwatersrand, Faculty of Health Sciences, 1997.

(no abstract available)

The safety of antipsychotic use in elderly persons has recently been questioned. The incidence of adverse events (AEs) (extrapyramidal syndromes (EPS), cerebrovascular and cardiac events, and all-cause mortality) in the elderly users of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) was compared. Risks of AEs in antipsychotic-exposed persons and non-exposed individuals were also assessed. A population-based retrospective cohort study was conducted in the elderly Manitoba residents who received their first antipsychotic medication between April 1, 2000 and March 31, 2007. Cox proportional hazards models were built to compare risks of AEs in FGA and SGA users, as well as in non-exposed subjects. SGAs were associated with a lower risk of all-cause mortality (adjusted HR 0.683, 95% CI 0.577–0.809) and a higher risk of myocardial infarction (1.614 [1.024–2.543]) compared to FGAs. No significant differences between FGAs and SGAs were found for cerebrovascular events, cardiac arrhythmia and congestive heart failure (CHF) but a higher incidence of EPS was observed for FGAs compared to risperidone. Both FGA and SGA users were at a higher risk of cerebrovascular events (FGAs 1.415 [1.114–1.797]; SGAs 1.611 [1.388–1.869]) and CHF (FGAs 1.228 [0.893–1.689]; SGAs 1.242 [1.003–1.536]) compared to non-exposed subjects. Only FGA-users were at a higher risk of death compared to non-exposed subjects (FGAs 1.387 [1.065–1.805]; SGAs 0.824 [0.708–0.959]). Both FGA and risperidone use were associated with a higher risk of EPS (FGAs 3.503 [2.271–5.403]; risperidone 1.733 [1.214–2.472]). Both classes of antipsychotics might lead to potentially life-threatening AEs. Neither FGAs nor SGAs seem to have a superior overall safety profile. Antipsychotic pharmacotherapy should be prescribed in elderly persons after careful consideration of all risks and benefits.

The safety of antipsychotic use in elderly persons has recently been questioned. The incidence of adverse events (AEs) (extrapyramidal syndromes (EPS), cerebrovascular and cardiac events, and all-cause mortality) in the elderly users of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) was compared. Risks of AEs in antipsychotic-exposed persons and non-exposed individuals were also assessed. A population-based retrospective cohort study was conducted in the elderly Manitoba residents who received their first antipsychotic medication between April 1, 2000 and March 31, 2007. Cox proportional hazards models were built to compare risks of AEs in FGA and SGA users, as well as in non-exposed subjects. SGAs were associated with a lower risk of all-cause mortality (adjusted HR 0.683, 95% CI 0.577–0.809) and a higher risk of myocardial infarction (1.614 [1.024–2.543]) compared to FGAs. No significant differences between FGAs and SGAs were found for cerebrovascular events, cardiac arrhythmia and congestive heart failure (CHF) but a higher incidence of EPS was observed for FGAs compared to risperidone. Both FGA and SGA users were at a higher risk of cerebrovascular events (FGAs 1.415 [1.114–1.797]; SGAs 1.611 [1.388–1.869]) and CHF (FGAs 1.228 [0.893–1.689]; SGAs 1.242 [1.003–1.536]) compared to non-exposed subjects. Only FGA-users were at a higher risk of death compared to non-exposed subjects (FGAs 1.387 [1.065–1.805]; SGAs 0.824 [0.708–0.959]). Both FGA and risperidone use were associated with a higher risk of EPS (FGAs 3.503 [2.271–5.403]; risperidone 1.733 [1.214–2.472]). Both classes of antipsychotics might lead to potentially life-threatening AEs. Neither FGAs nor SGAs seem to have a superior overall safety profile. Antipsychotic pharmacotherapy should be prescribed in elderly persons after careful consideration of all risks and benefits.

This thesis studies existence and characterization of optimal solutions to the principal-agent problem with adverse selection for both discrete and continuous problems. The existence results are derived by the abstract concepts of differentiability and convexity. Under the Spence Mirrlees condition, we show that the discrete problem reduces to a problem that always satisfies the linear independence constraint qualification, while the continuum of type problem becomes an optimal control problem. We then use the Ellipsoid algorithm to solve the problem in the discrete and convex case. For the problem without the Spence Mirrlees condition, we consider different classes of constraint qualifications. Then we introduce some easy-to-check conditions to verify these constraint qualifications. Finally we give economic interpretations for several numerical examples. / Graduate

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