This thesis describes the creation of substituted diphenylacetic acids and their results.

Thesis submitted to the Faculty of Science, University of the Witwatersrand, in fulfilment of the requirement for the degree of Doctor of Philosophy 2019 School of Public Health University of the Witwatersrand, South Africa / Background: Spatial targeting of interventions is increasingly recognized as essential for malaria control, particularly in areas aiming for elimination. The associations between house characteristics and malaria transmission is known, but gaps remain on whether transmission is also influenced by factors such as distances between households or the degree to which houses are clustered. It is also important to identify new interventions that can be implemented by targeting critical points in the biology of major malaria vectors and common characteristics of human settlements. Such efforts will be essential to complement current major tools. Aims: This study had the following aims; (i) understand how households densities and their distances influence malaria transmission the study area , (ii) identify housing-related factors affecting residual transmission risks in the area (iii) assess opinions of residents on how house characteristics, settlement patterns and other environmental factors influencing malaria transmission, and (iv) identify effective complementary approaches that could be used to improve malaria control in these residual transmission area with high coverage of basic interventions such as long lasting treated nets. Methodology: A mixed methods approach was used, which included: (i) indoor and outdoor mosquito collections from fixed as well as randomly selected households over 12 months, (ii) characterization of physical and microclimatic conditions of the houses and surrounding environmental variables, (iii) assessing effects of spatial clustering of households on malaria transmission risks, and (iv) assessing community concerns regarding household and environmental factors influencing transmission. During these studies, swarms of Anopheles mosquitoes were discovered for the first time in this area. Therefore, additional quantitative and qualitative observations were made to characterize the swarms and assess how they could be targeted to complement malaria control efforts. Key findings: Despite the expansive use of LLINs in the area, factors associated with housing characteristics and settlement patterns as well as people’s perceptions contribute to persistent malaria transmission, and will need to be addressed for eventual elimination to be reached. The main findings of this study were as follows: (i) household occupancy influenced indoor mosquito density (ii) high house densities increased Anopheles biting risk but mosquito density declined as distances between houses increased beyond 50m; (iii) abundance of the vector Anopheles arabiensis peaked during high rainfall months (February-May), but An. funestus densities remained stable into the dry season (May-August); (iv) there were higher indoor densities of An. arabiensis and An. funestus in houses with mud walls compared to plastered or brick walls, open eaves compared to closed eaves and unscreened windows compared to screened windows; (v) most respondents were aware of associations between their house characteristics and malaria risks but carrying out improvements was constrained by financial costs and other household priorities; (vi) in all our surveys, An. funestus mosquitoes contributed approximately 85% of ongoing malaria transmission in the areas, even when occurring in far smaller densities than An. arabiensis; and (vii) with regards to complementary interventions, small scale studies demonstrated that mating swarms of both An. arabiensis and An. funestus could be readily identified and characterized (in this case by volunteer community members), and that targeting the swarms using aerosol spraying could possibly reduce overall biting risk in the communities. Conclusions: This study yielded evidence that malaria transmission risks are significantly lower when the distances between houses are high. Variation in malaria transmission risk within a village might be important for planning and implementing spatially targeted interventions. With limited resources, malaria control efforts must be prioritized in locations with significantly higher risk in order to obtain maximum benefit. Thus, the distances between houses should be considered when planning malaria vector control strategies. Furthermore, the overall clustering of indoor densities of major disease-transmitting mosquitoes is significantly associated with household occupancy and its spatial distribution within the villages. Further research is needed to assess the potential of using this information for predicting, identifying and targeting the most intense foci of mosquito-borne disease transmission based on household occupancy. Understanding the factors influencing malaria transmission at a small scale is crucial for planning malaria control interventions. Malaria transmission heterogeneity does not only exist on a large scale, but also at small scales, which may be influenced by small variations of environmental features, such as seasonality. These variations should be considered when improving malaria control interventions. While An. funestus showed variation in density during the year, numbers of mosquitoes remained high throughout the dry season, whereas An. arabiensis showed a definite peak in the rainy season with a subsequent drop during the dry season. Further studies are required to investigate the survival strategies of major malaria vectors during the dry season. Understanding this particular feature of An. funestus may lead to the design of new control strategies or improve existing interventions so as to reduce the malaria burden in such rural areas. This study also documented high mosquito densities in mud-walled houses compared to houses with brick or plastered walls. These findings further indicate the necessity of considering house improvement as a malaria control strategy. While the community members had fairly high awareness that improved houses were associated with reduced mosquito nuisance, many families in rural areas are living in poorly constructed houses. It is therefore necessary to consider inter-sectoral collaborations to integrate housing into health policies in Tanzania. Further studies are also needed to provide epidemiological evidence on how housing design affects malaria transmission. Furthermore, community-based house improvement programs should be promoted, including simple, scalable and affordable house improvements for the populations living in high malaria endemic areas in rural communities. Generally, this study has generated information which sets the basis for further studies on the relationship between the exact house location and malaria transmission risk in rural malaria endemic countries. / MT 2020

The fate and transport of insoluble, hydrophobic organic pollutants in the aquatic environment constitutes a prominent area of concern. It is thought that pollutants of this nature may exist in association with organic carbon, which is predominantly aquatic humus. This type of association could significantly affect the kinetics of such transformation processes as volatilization or chemical and biological degradation of the pollutant. While dissolved organic matter (DOM) comprises the bulk of organic carbon (or aquatic humus) in natural waters, the interaction between naturally occurring DOM and insoluble organic pollutants has not been quantified. The work presented in this dissertation is an effort to quantify the effect of dissolved organic matter on the solubility in water and, hence, the transport of hydrophobic organic compounds (specifically, DDT) in the environment. Saturated aqueous solutions of DDT were generated by a method that is different from those used by other workers. Within a closed system, an excess of solid DDT was allowed to vaporize and enter an aqueous solution through the gas phase. The concentration of DDT in solution increased with time, leveling off when equilibrium and a saturated solution was established. The solubility of p,p'-DDT in distilled water was determined to be 1.87 (+OR-) .01 ppb. The solubility of the o,p'-DDT isomer in distilled water was determined to be 4.88 (+OR-) .03 ppb. The concentrations of p,p'-DDT and o,p'-DDT in distilled water solutions containing dissolved organic matter were definitely higher than the aqueous solubilities of these compounds. A minimum value for the DDT/DOM partition coefficient (K(,p)) in water was determined. This partition coefficient, when normalized to organic carbon, is referred to as K(,oc) (K(,oc) = K(,p)/fraction organic carbon). A minimum log K(,oc) for both p,p'-DDT and o,p'-DDT was determined to be 4.7 (+OR-) .2 log units. Under environmental conditions, this partition coefficient indicates that the majority of DDT present in aqueous systems will be associated with dissolved organic matter.

Obesity is a growing concern in the world today. As we ponder about the many causes of this global epidemic, we are driven to look at our food and the environmental toxicants that may contribute to obesity. Deltamethrin, being a common synthetic pyrethroid used in agriculture for pest control, is the primary insecticide this study explores to connect with obesity in 3T3-L1 adipocytes. To investigate the relationship between deltamethrin and adipogenesis, various concentrations were tested, 1nM, 10nM, 100nM, 1μM, and 10μM. The result indicated that higher concentration of deltamethrin had a direct impact on fat accumulation. These experiment results indicate that deltamethrin may potentiate adipogenesis in this model. Further in vivo studies will be needed to validate these findings and confirm the effects of deltamethrin on obesity.

No description available.

No description available.

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The resistance status of Tetranychus urticae Koch and Lygus hesperus Knight sourced from California strawberry fields was evaluated in laboratory bioassay experiments. Adult female T. urticae sourced from a miticide naïve population were exposed to a range of miticide active ingredient concentrations mixed with acetone in contact bioassay experiments. LC50 concentrations for the active ingredients fenpyroximate, abamectin, bifenazate, and spiromesifen as well as LC90 concentrations for the active ingredients fenpyroximate, abamectin, and bifenazate were derived from this susceptible population. A total of ten field populations of T. urticae, five from the Santa Maria growing region and five from the Ventura/Oxnard growing region, were exposed to these concentrations and mortality response was compared with the susceptible population to determine the resistance status of T. urticae on a per-field basis. Resistance detection occurred less often in the LC50 concentration groups compared to their respective LC90 concentrations. Resistance to the LC50 concentration of spiromesifen could not be detected in any field population. Resistance to the LC90 concentrations of fenpyroximate and abamectin was detected in three field populations from Santa Maria and four populations from Ventura/Oxnard. Resistance to the LC90 concentration of bifenazate was detected in three populations from Ventura/Oxnard and in no populations from Santa Maria. Lygus hesperus were exposed to formulated products registered in California strawberries after being separated into three groups based on life stage. Instars one through three were considered small, instars four and five were considered large, and winged individuals were considered adults. The small and large groups were exposed to the maximum field labeled rate of Rimon® (a.i. = novaluron). Adults were exposed to the maximum field labeled rate of Actara®, Brigade®, and Sivanto®, the active ingredients of which are thiamethoxam, bifenthrin, and flupyradifurone respectively. A total of 14 field populations were screened for resistance, six collected from the Santa Maria growing region in 2021, and eight collected in 2022, five of which came from the Santa Maria region, and three from the Salinas/Watsonville region. Resistance was detected by comparing the mortality response of an insecticide naïve population of L. hesperus and field collected populations in residual laboratory bioassay experiments. Resistance to Rimon® in the small group was effectively detected in all populations in 2021 and 2022. Resistance to Rimon® in the large group was detected in four populations in 2021 and five populations in 2022. Resistance to Actara® and Brigade® was effectively detected in all populations in 2021 and 2022. Resistance to Sivanto® was effectively detected in four populations in 2021 and two of three populations in 2022. A full submersion assay was utilized for the second half of Sivanto® trials in 2022 since mortality response of the susceptible population was low in the residual group. Five of five populations tested with the modified assay were considered effectively resistant.

Three reaction paths (Charts II, III and IV) have been shown for the preparation of the following three compounds which are of interest because they are structurally related to DB2: 9â tri-chlormethylanthracene, 3-chloro-9-â ¢trichlomethylanthracene and 2,7-dichloro·10-trichlomethylanthracene. / Master of Science

The honey bee, Apis mellifera, provides about $15 billion USD in crop value each year in the U.S. alone in the form of pollination services. Since 2006, commercial beekeepers have reported an average annual overwintering loss of about 28.6% of all managed colonies. There are many factors that are thought to contribute to colony loss including bee-specific pests (e.g. the Varroa destructor mite), bee-specific pathogens (e.g. Nosema fungus), modern beekeeping practices, diminished genetic variability, poor queens, climate change, and exposure to agricultural pesticides. While not the single cause of colony loss, the neonicotinoid insecticides elicit sublethal effects to honey bees that could increase their sensitivities to other stressors that affect colony health. Previous studies found that honey bees have differential sensitivities to the neonicotinoid insecticide imidacloprid, which suggest a mechanism of tolerance to the insecticide in certain colonies. In this study, I examined the imidacloprid sensitivity of honey bees collected from different colonies. After determining a range of LC50 values in the tested colonies, I examined the metabolic detoxification activities of honey bees collected from two colonies that represented the highest and lowest LC50 values, between which there was a 36-fold difference in their LC50 values. I discovered that of the three main families of metabolic detoxification enzymes, general esterases, cytochrome P450 monooxygenases, and glutathione S-transferases (GSTs), a reduction of GST activity with diethyl maleate (DEM) significantly increased imidacloprid-mediated mortality to the honey bees. A comparative analysis of GST kinetic activity from imidacloprid-susceptible and -insensitive honey bees revealed a lower bimolecular inhibition rate constant (ki) for imidacloprid-insensitive individuals (5.07 ± 0.098 nmol/min/mg protein) compared to the imidacloprid-sensitive honey bees (17.23 ± 1.235 nmol/min/mg protein). The IC50 of DEM estimated for bees from each colony showed that the imidacloprid-susceptible honey bees possess a higher IC50 (10 μM) than that of the tolerant honey bees (3 μM). These data suggest that the GSTs in the imidacloprid-tolerant honey bees might be a more efficient detoxification mechanism for the conjugation and elimination of imidacloprid, or imidacloprid metabolites, compared to that of imidacloprid-susceptible honey bees. Therefore, I hypothesize that the differences in metabolic detoxification enzyme activities of honey bees collected from different colonies can result in the differential toxicities of honey bees exposed to neonicotinoid insecticides, such as imidacloprid. However, a thorough examination of imidacloprid detoxification in honey bees is warranted to confirm this hypothesis. / Master of Science in Life Sciences