Matching Items (7)

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Beginning to investigate Lactase Persistence in Turkana

Description

Lactase persistence is the ability of adults to digest lactose in milk (Segurel & Bon, 2017). Mammals are generally distinguished by their mammary glands which gives females the ability to produce milk and feed their newborn children. The new born

Lactase persistence is the ability of adults to digest lactose in milk (Segurel & Bon, 2017). Mammals are generally distinguished by their mammary glands which gives females the ability to produce milk and feed their newborn children. The new born therefore requires the ability to breakdown the lactose in the milk to ensure its proper digestion (Segurel & Bon, 2017). Generally, humans lose the expression of lactase after weaning, which prevents them being able to breakdown lactose from dairy (Flatz, 1987).
My research is focused on the people of Turkana, a human pastoral population inhabiting Northwest Kenya. The people of Turkana are Nilotic people that are native to the Turkana district. There are currently no conclusive studies done on evidence for genetic lactase persistence in Turkana. Therefore, my research will be on the evolution of lactase persistence in the people of Turkana. The goal of this project is to investigate the evolutionary history of two genes with known involvement in lactase persistence, LCT and MCM6, in the Turkana. Variants in these genes have previously been identified to result in the ability to digest lactose post-weaning age. Furthermore, an additional study found that a closely related population to the Turkana, the Massai, showed stronger signals of recent selection for lactase persistence than Europeans in these genes. My goal is to characterize known variants associated with lactase persistence by calculating their allele frequencies in the Turkana and conduct selection scans to determine if LCT/MCM6 show signatures of positive selection. In doing this, we conducted a pilot study consisting of 10 female Turkana individuals and 10 females from four different populations from the 1000 genomes project namely: the Yoruba in Ibadan, Nigeria (YRI); Luhya in Webuye, Kenya; Utah Residents with Northern and Western European Ancestry (CEU); and the Southern Han Chinese. The allele frequency calculation suggested that the CEU (Utah Residents with Northern and Western European Ancestry) population had a higher lactase persistence associated allele frequency than all the other populations analyzed here, including the Turkana population. Our Tajima’s D calculations and analysis suggested that both the Turkana population and the four haplotype map populations shows signatures of positive selection in the same region. The iHS selection scans we conducted to detect signatures of positive selection on all five populations showed that the Southern Han Chinese (CHS), the LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations had stronger signatures of positive selection than the Turkana population. The LWK (Luhya in Webuye, Kenya) and the YRI (Yoruba in Ibadan, Nigeria) populations showed the strongest signatures of positive selection in this region. This project serves as a first step in the investigation of lactase persistence in the Turkana population and its evolution over time.

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Date Created
2019-05

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Correlation between Larvicide Susceptibility and Quiescence in Aedes aegypti

Description

Mosquitoes are estimated to kill roughly 700,000 people each year through the transmission of vector-borne diseases. Vector control via insecticides is a widely used method in order to combat the spread of mosquito populations; however, this comes at a cost.

Mosquitoes are estimated to kill roughly 700,000 people each year through the transmission of vector-borne diseases. Vector control via insecticides is a widely used method in order to combat the spread of mosquito populations; however, this comes at a cost. Resistance to insecticides has the potential to increase vector-borne disease rates. Aedes aegypti is an invasive mosquito species in Arizona and is a known potential vector for a variety of infectious diseases including dengue, chikungunya, Zika, and yellow fever. In contrast to many other mosquito species Ae. aegypti mosquito eggs can undergo quiescence, an active state of dormancy, over long periods of time. Variation in quiescent periods correlates to climatic rainfall alterations and can ultimately influence hatching and mating between multiple generations. I have studied the effect of quiescence on larvicide (i.e., temephos) susceptibility using mosquito eggs collected from a susceptible lab strain and stored under optimal temperature and humidity conditions. After undergoing various quiescent periods (3, 7, 14, 28, 84, and 182 days), the experimental eggs as well as 7-day quiescent control eggs were hatched and reared to 3rd instar larvae. Temephos susceptibility was tested using the WHO bioassay procedure at lethal concentration (LC) 20, LC50, LC80, diagnostic dose (twice LC99), plus an untreated control. Each concentration dose was replicated four times with 20 larvae each. The 3-day experimental group was excluded from analysis because the mortality was significantly lower than the 7-day for both the experimental and control groups. The 3 day experimental eggs displayed decreased mortality which did not align with the hypothesis, as the quiescence period elongates under optimal conditions, susceptibility to insecticides decreases, and this could have likely resulted from unintentional selection for increased fitness and faster developing eggs because the larvae that developed to 3rd instar first were those used for larvicide testing. ANOVA testing demonstrates variability in the LC80 experimental group which suggests the need for further investigation into high dose temephos concentrations. For the experimental LC20 linear regression, there were significant differences in mortality. The results indicate mortality gradually decreases when the quiescence period elongates, therefore there are significant differences in insecticide susceptibility when quiescence is 182 days (or longer), compared to when quiescence is 7 days. Further investigation into field mosquito’s genetic diversity, insecticide resistance profile, and environmental conditions should be considered.

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2021-05

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Evaluating the Effects of Temperature on the Toxicity of Insecticides That Target Arbovirus Vectors in the Phoenix Metropolitan Area

Description

Despite its well-documented preference for much more humid climates, the yellow fever mosquito, or Aedes aegypti, has inhabited Arizona since 1951. Their presence is of great concern as they can transmit many deadly diseases, including yellow fever, chikungunya, Zika, and

Despite its well-documented preference for much more humid climates, the yellow fever mosquito, or Aedes aegypti, has inhabited Arizona since 1951. Their presence is of great concern as they can transmit many deadly diseases, including yellow fever, chikungunya, Zika, and dengue fever, putting the residents of the Phoenix Metropolitan Area at risk. Maricopa County Vector Control has made an extensive effort to reduce this risk mainly through the act of fogging insecticides during the night in areas where mosquito numbers exceed a threshold. However, given the well-known temperature-toxicity relationships in insect species, fogging at night may be less or more effective —depending on the relationship— due to the colder temperatures at these times. Additionally, insecticide resistance testing has always been performed at temperatures not usually experienced during fogging, adding to the uncertainty on how useful those test outcomes are. This study took the first steps in determining the effects of temperature on the toxicity of a commonly used insecticide, deltamethrin, on Aedes aegypti by developing a dose response curve on a lab strain at a standard lab temperature of 25°C by performing a CDC bottle bioassay. The diagnostic dose was found to be 50 μg/mL and the lethal dose, 50% (LD50, the dose required to kill half of the test mosquitoes) was found to be 9 μg/mL. Future testing would need to be completed to compare the deltamethrin dose response curve developed in this study with deltamethrin dose response curves at various different temperatures.

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Date Created
2020-05

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Aedes aegypti Thermal Choice Experiment

Description

The non-native mosquito Aedes aegypti has become a common nuisance in Maricopa county. Associated with human settlement, Ae. aegypti is known to reproduce in standing water sources both indoors and outdoors, within vessels such as tires, flowerpots, and neglected swimming

The non-native mosquito Aedes aegypti has become a common nuisance in Maricopa county. Associated with human settlement, Ae. aegypti is known to reproduce in standing water sources both indoors and outdoors, within vessels such as tires, flowerpots, and neglected swimming pools (Jansen & Beebe, 2010). Ae. aegypti and the related Ae. albopictus are the primary vectors of the arboviral diseases chikungunya, Zika, yellow fever and dengue. Ae. aegypti tends to blood feed multiple times per gonotrophic cycle (cycle of feeding and egg laying) which, alongside a preference for human blood and close association with human habitation, contributes to an increased risk of Ae. aegypti borne virus transmission (Scott & Takken, 2012). Between 2010-2017, 153 travel-associated cases of dengue were reported in the whole of Arizona (Rivera et al., 2020); while there have been no documented locally transmitted cases of Aedes borne diseases in Maricopa county, there are no apparent reasons why local transmission can’t occur in the future via local Aedes aegypti mosquitoes infected after feeding from travelling viremic hosts. Incidents of local dengue transmission in New York (Rivera et al., 2020) and Barcelona (European Center for Disease Control [ECDC], 2019) suggest that outbreaks of Aedes borne arbovirus’ can occur in regions more temperate than the current endemic range of Aedes borne diseases. Further, while the fact that Ae. aegypti eggs have a high mortality rate when exposed to cold temperatures limits the ability for Ae aegypti to establish stable breeding populations in temperate climates (Thomas, Obermayr, Fischer, Kreyling, & Beierkuhnlein, 2012), global increases in temperature will expand the possible ranges of Ae aegypti and Aedes borne diseases.

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Date Created
2020-05

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Mathematical Modeling of Systematic Treatment Implementation and Dynamics of Neglected Tropical Diseases: Case Studies of Visceral Leishmaniasis & Soil-Transmitted Helminths

Description

Neglected tropical diseases (NTDs) comprise of diverse communicable diseases that affect mostly the developing economies of the world, the “neglected” populations. The NTDs Visceral Leishmaniasis (VL) and Soil-transmitted Helminthiasis (STH) are among the top contributors of global mortality and/or morbidity.

Neglected tropical diseases (NTDs) comprise of diverse communicable diseases that affect mostly the developing economies of the world, the “neglected” populations. The NTDs Visceral Leishmaniasis (VL) and Soil-transmitted Helminthiasis (STH) are among the top contributors of global mortality and/or morbidity. They affect resource-limited regions (poor health-care literacy, infrastructure, etc.) and patients’ treatment behavior is irregular due to the social constraints. Through two case studies, VL in India and STH in Ghana, this work aims to: (i) identify the additional and potential hidden high-risk population and its behaviors critical for improving interventions and surveillance; (ii) develop models with those behaviors to study the role of improved control programs on diseases’ dynamics; (iii) optimize resources for treatment-related interventions.

Treatment non-adherence is a less focused (so far) but crucial factor for the hindrance in WHO’s past VL elimination goals. Moreover, treatment non-adherers, hidden from surveillance, lead to high case-underreporting. Dynamical models are developed capturing the role of treatment-related human behaviors (patients’ infectivity, treatment access and non-adherence) on VL dynamics. The results suggest that the average duration of treatment adherence must be increased from currently 10 days to 17 days for a 28-day Miltefosine treatment to eliminate VL.

For STH, children are considered as a high-risk group due to their hygiene behaviors leading to higher exposure to contamination. Hence, Ghana, a resource-limited country, currently implements a school-based Mass Drug Administration (sMDA) program only among children. School staff (adults), equally exposed to this high environmental contamination of STH, are largely ignored under the current MDA program. Cost-effective MDA policies were modeled and compared using alternative definitions of “high-risk population”. This work optimized and evaluated how MDA along with the treatment for high-risk adults makes a significant improvement in STH control under the same budget. The criticality of risk-structured modeling depends on the infectivity coefficient being substantially different for the two adult risk groups.

This dissertation pioneers in highlighting the cruciality of treatment-related risk groups for NTD-control. It provides novel approaches to quantify relevant metrics and impact of population factors. Compliance with the principles and strategies from this study would require a change in political thinking in the neglected regions in order to achieve persistent NTD-control.

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Date Created
2020

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Mathematical Assessment of Control Measures Against Mosquito-borne Diseases

Description

Mosquitoes are the greatest killers of mankind, and diseases caused by mosquitoes continue to induce major public health and socio-economic burden in many parts of the world (notably in the tropical sub-regions). This dissertation contributes in providing deeper qualitative insights

Mosquitoes are the greatest killers of mankind, and diseases caused by mosquitoes continue to induce major public health and socio-economic burden in many parts of the world (notably in the tropical sub-regions). This dissertation contributes in providing deeper qualitative insights into the transmission dynamics and control of some mosquito-borne diseases of major public health significance, such as malaria and dengue. The widespread use of chemical insecticides, in the form of long-lasting insecticidal nets (LLINs) and indoor residual spraying, has led to a dramatic decline in malaria burden in endemic areas for the period 2000-2015. This prompted a concerted global effort aiming for malaria eradication by 2040. Unfortunately, the gains recorded are threatened (or not sustainable) due to it Anopheles resistance to all the chemicals embedded in the existing insecticides. This dissertation addresses the all-important question of whether or not malaria eradication can indeed be achieved using insecticides-based control. A novel mathematical model, which incorporates the detailed Anopheles lifecycle and local temperature fluctuations, was designed to address this question. Rigorous analysis of the model, together with numerical simulations using relevant data from endemic areas, show that malaria elimination in meso- and holo-endemic areas is feasible using moderate coverage of moderately-effective and high coverage of highly-effective LLINs, respectively. Biological controls, such as the use of sterile insect technology, have also been advocated as vital for the malaria eradication effort. A new model was developed to determine whether the release of sterile male mosquitoes into the population of wild adult female Anopheles mosquito could lead to a significant reduction (or elimination) of the wild adult female mosquito population. It is shown that the frequent release of a large number of sterile male mosquitoes, over a one year period, could lead to the effective control of the targeted mosquito population. Finally, a new model was designed and used to study the transmission dynamics of dengue serotypes in a population where the Dengvaxia vaccine is used. It is shown that using of the vaccine in dengue-naive populations may induce increased risk of severe disease in these populations.

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Date Created
2020

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Roof Tube: Developing a Device to Reduce Indoor Temperatures and Improve Air Quality of Corrugated Roofed Homes in Developing Nations

Description

This study documents and explores the process of designing a device to decrease the indoor temperature and particulate matter concentration in the air of corrugated steel homes in sub-Saharan Africa. The device, named the Roof Tube, generates power from a

This study documents and explores the process of designing a device to decrease the indoor temperature and particulate matter concentration in the air of corrugated steel homes in sub-Saharan Africa. The device, named the Roof Tube, generates power from a solar panel that goes towards powering a motor that rotates blades to output a desired airflow to draw air out from the inside environment. Excess power generated goes towards charging a battery pack during the day that then powers the motor and a light (to improve indoor living quality) during the night when the solar panel cannot collect any more energy. Calculations were done to estimate the ambient indoor temperature of a model home based on the heat transfer from the sun. From this, a rough airflow was determined to offset the temperature difference between the indoor and outdoor environment. A computational fluid dynamics test was performed to determine the effectiveness of the housing design. Results from all tests displayed a low difference between outdoor and indoor temperatures leading to a low prediction of outlet airflow. The designed device prioritized effectiveness, it displaces air at 2700 cfm and charges a 54000mAh battery pack that, when solar energy generation is cut off, can power the motor and light simultaneously for on average 3.02 hours, the motor alone for 8.88 hours, and the light alone for 4.57 hours.

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Date Created
2022-05