Alumni

2011 Delta Omega Scholarship Winners

Five winners were chosen.

Applied:

Talia Abbott Chalew, PhD Student
Stability, Treatability, and Toxicity of Engineered Nanoparticles in Natural Waters.

Engineered nanoparticles (NP) are currently used in many consumer products without a full understanding of their environmental fate. According to the Project on Emerging Nanotechnology’s inventory, silver, zinc oxide, and titanium dioxide NPs are commonly incorporated into personal care products, food storage containers, and clothing. These NP-containing products may release NPs into the domestic waste stream and surface waters during their production, usage, cleaning, and final disposal. For example, titanium dioxide NPs were found in urban streams after rain events that washed these NPs off of the outdoor NP- containing house paints.

The ultimate fate of NPs released into the aquatic environment – whether they remain suspended in the water, settle onto the sediment, or completely dissolve – is currently unknown.  Transport of NPs in water is affected by NP dissolution, aggregation, and sedimentation. These processes are affected by characteristics of the water and the NPs themselves.

Humans may be exposed to NPs by ingestion of NPs contained in food and water, by dermal absorption from NP-containing personal care products, and by inhalation of NPs in the air. Through laboratory studies, NPs have been shown to induce cell death and increase reactive oxygen species, which can lead to inflammation.  It is likely that NPs will be released to surface waters and therefore, humans may be exposed through drinking water – especially if drinking water treatment does not fully remove these NPs. Yet the health effects of ingested NPs, especially at environmentally relevant concentrations, are largely unknown.

My research will help address these knowledge gaps by investigating NP stability in water, removal during drinking water treatment, and toxicity to human intestinal cell lines. This project will investigate how silver, titanium dioxide, and zinc oxide NPs behave in reagent grade and real surface waters, which will increase our understanding of NP transport and persistence in drinking water sources. The efficiency of drinking water treatments on removing NPs from surface waters will also be investigated for an understanding of the potential dose of NPs that humans may ingest in finished drinking water. Using in vitro experiments, this project will explore the toxicity of NPs on human intestinal cells following NP exposures. 

For this research project, commercially available silver, titanium dioxide, and zinc oxide nanoparticles will be purchased. Both dry nanopowders and stock suspensions of the NPs in waters will be characterized, including measurements of the size, shape, metal content, and zeta potential using dynamic light scattering (DLS), inductively coupled plasma mass spectroscopy (ICP-MS), and scanning and transmission electron microscopy (SEM and TEM). NPs will be characterized at each step of the experiments for a greater understanding of the NP properties, since environmental fate depends on NP size characteristics. Characterization of NPs in the waters and cell culture media will provide information on the ‘as dosed’ particles, as recommended by Powers, et al.

Once characterized, the NP stock will be diluted into reagent grade and natural freshwaters in the range of estimated environmental concentrations. The size and concentrations of NPs in the waters over time will be investigated in order to understand how NP stability may change over time. The kinetics of aggregation and sedimentation inform our understanding of how NPs will behave in the aquatic environment, and provide data on the NP concentrations and sizes in raw drinking waters. These results can be used to recommend the appropriate drinking water treatments needed to remove NPs. 

This project will assess the removal of NPs using conventional and advanced drinking water treatment in the lab by mimicking the processes commonly used in water treatment plants. Water spiked with NPs will be treated using a traditional flocculation/sedimentation system as well as advanced membrane filtration. Treated water will be analyzed using DLS and ICP-MS to determine size and concentration of remaining NPs in the drinking water that humans might ingest. These results can inform decisions about the most effective drinking water treatment to remove NPs.

Using in vitro cell culture methods, the toxicity of NPs following ingestion via drinking water will be investigated in the laboratory. The project will focus on the Caco-2 human cell line, which is derived from large intestine cells, but simulates the small intestine. Following NP exposures, toxicity will be probed by measuring cell death, change in cell morphology, cell uptake of nanoparticles, and generation of reactive oxygen species.

My doctoral research will provide an indication of the fate of three common NPs in natural waters, their likelihood to contaminate drinking water resources, removal under current drinking water treatment, and the toxicity of NPs to human intestinal cells. NPs are an important emerging contaminant in drinking water, and one that must be addressed in the near future. This project will address important research questions including NP environmental fate, presence in drinking water, and potential human exposures. The results of this project may be used to influence policy and practice to ensure safe drinking water and to minimize human exposures to NP ingestion. This scholarship will help provide funds to complete my research.

Practice:

Maria Au, DrPH Student
Ethnic and Generational Differences in Lifestyle Patterns and Their Effects on Obesity among U.S. Adults in California

Introduction/Goals

The prevalence of overweight and obesity in the United States has risen markedly in the past three decades.  Between 1980 and 2008, obesity prevalence doubled in adults aged 20 years or older.  Most recent studies demonstrated that 68% of the adult population in the U.S. is either overweight or obese. Ethnic minorities, especially African American and Latino populations, are at greater risk for obesity and concomitant dietary and physical activity patterns, and bear an increasingly disproportionate chronic disease burden compared to their White counterparts.  To date, studies targeting Asian Americans on these issues have been scarce and most population-based data do not provide sufficient sample size for Asian Americans to assess these lifestyle patterns. To further complicate the existing ethnic disparities in obesity, many ethnic minorities, with the exception of non-Hispanic African Americans, are first generation immigrants from countries where the prevalence of obesity is lower than the U.S., and as a population, are in better health than their counterparts born in the U.S. However, these differences in better health outcomes and healthy behaviors dissipate with the increase in duration of residence in the U.S and the factors associated with this decline in health have not been well examined.

The goal of this study is to explore the ethnic and generational differences in lifestyle patterns among minority adults, and to assess the effects these disparities have on overweight/obesity among these populations in California. Specifically, research questions are as follow: 1) What are the differences in dietary pattern, level of physical activity, and obesity among Latino, African American, and Asian American adults compared to White adults? 2) What are the lifestyle pattern changes among Latino and Asian American adults with longer duration of residence in the U.S.?  3) Is there a difference in regards to the association of lifestyle patterns with obesity among the various racial/ethnic adult populations?

Methods

A secondary analysis of two different sets of population-based cross-sectional surveys, the 2001 and 2007 California Health Interview Surveys (CHIS) and the 2002 and 2007 Los Angeles County Health Surveys (LACHS) will be performed. All adults aged 18 or older residing in California at the time of the interview who classified themselves as either Non-Hispanic White, Latino, African American or Asian American/Native Hawaiian/Pacific Islander in the CHIS and LACHS data will be included. These surveys will be geocoded and linked to the 2000 Census data, InfoUSA food environment data, and spatial data on physical environment from local county public database, to assess the neighborhood and county level factors.  It will utilize multilevel (hierarchical) regression techniques to estimate the differences in the effects of lifestyle pattern on obesity risk among Non-Hispanic White, African American, Hispanic white, and Asian American adults aged 18 or older in California on the individual, neighborhood, and county levels.

The assessment of physical food environment will be conducted using InfoUSA database, a comprehensive commercial database of approximately 14 million private and public U.S. companies that are located by address geocodes, and will be spatially linked at the census tract and county levels in this study.  Using the North American Industry Classification System, the types of food outlets included in the InfoUSA database will be classified into fast-food outlets, full service restaurants, supermarkets/grocery stores, small food stores, and produce vendors.

Physical environment data to assess neighborhood walkability will be obtained from the local county departments of urban planning derived from Geographic Information Systems (GIS).  Individuals’ home address (or cross streets) from the CHIS and LACHS will be geocoded and a one mile network buffer around their residence will be created using ArcGIS 9.1 software.

Significance

The results of this study are expected to impact public health programs and policy at different levels.  Because the risk of overweight and its related co-morbidities have risen dramatically over the past 20 years, with striking health disparities between minorities and the overall U.S. population, exploring the issue of the determinants of these disparities on obesity is timely and important.  Between 1990 and 2000, the U.S. experienced an increase in population that was disproportionally higher among foreign-born populations (57% increase) compared to native born (9% increase) from 19.8 million to 31.1 million. Furthermore, it is projected that 87% of the population growth between 2005 and 2050 will be as a result of immigrants and their U.S-born children.  Given this shift in demographic perspective, understanding the determinants of obesity and other preventable chronic diseases among these growing minority populations is a public health concern for the U.S.  With ethnic minorities generally experiencing higher risks of obesity and engaging in unhealthy lifestyle patterns than whites, this proposal seeks to gain a better understanding of individual and racial predisposition and behavior, and neighborhood and county effects upon adult obesity, which could help shape the policy and programmatic responses for this issue.  Furthermore, given the scarcity of publication on lifestyle patterns among Asian Americans, the results of this study will add to the existing literature gap.  It is hoped that the findings will offer insight into how best to improve the effectiveness of ethnically targeted obesity-reduction interventions and will provide important information for policymakers to mitigate the issues with ethnic disparities, whether they be individual (i.e. access to insurance, health services), structural (i.e. lack of recreational area or walking path in neighborhood, access to healthy food), or environmental (i.e. neighborhood safety).

Budget

Measurement:

Maxwell Barffour, PhD Student
Quantification of the Extent of Malaria-induced Hyporetinolemia and Validation of the icheck^TM

Introduction  

Malaria is responsible for about 800 000 deaths in children each year and vitamin A deficiency (VAD) is responsible for about 20% of these deaths.   Situational assessment of childhood vitamin A status  in malaria endemic regions is therefore critical in reducing the burden of malaria morbidity and mortality. The validity of population level estimates of VAD is often threatened by inflammation-induced hyporetinolemia;- the transient but etiologically irrelevant reductions in retinol during the acute phase response to infections. Failure to account for this bias leads to non-reliable, elevated estimates of the actual burden of functional vitamin A deficiency. The extent of hyporetinolemia in the context of malaria-induced inflammation(MIn) is incompletely characterized. A recent meta-analyses estimated that this phenomenon may result in up to 30% inflation in the actual burden of VAD in malaria endemic regions. The procedure used in estimating this effect  is however questionable. The transient nature of malaria-induced hyporetinolemia warrants that in order to appropriately quantify the bias, assessment of vitamin A and malaria status should be done at least on two different occasion to incorporate the element of time. Unfortunately, all previous  studies on this subject were either cross-sectional or a meta-analysis of  cross-sectional studies. Such designs have the tendency to overestimate the bias owing to the clustering of other inflammation-inducing illnesses such as diarrhea and pneumonia among individuals and households in developing countries. The appropriate design is to follow the same group of individuals over time. Hence for the first time, we have proposed to use a longitudinal study to generate a correction factor to address this issue.

The lack of sensitive, feasible and affordable tools  is a major hindrance to the routine assessment of the burden of VAD in vulnerable populations. The WHO and the IVACG (International Vitamin A Consultative Groups) recommend serum or plasma retinol determined by High Pressure Liquid Chromatography(HPLC) as the standard for vitamin A determination. Unfortunately HPLC is expensive, time–consuming and often require a high degree of training and standard laboratory equipment to achieve reliable results.  There is an urgent need for  low cost technology to enable routine vitamin A assessment in low income countries where the burden is greatest. To this effect, BioAnalyt(Germany) has developed a portable flourometric  tool-icheckTM- for vitamin A assessment that requires only minimal training and  capable of producing results  within 10 minutes. Preliminary laboratory results showed that  the device is comparable to the conventional HPLC in terms of precision (correlation>0.9). It is critical that this novel technology be  validated in a population-based field setting before it is incorporated into routine vitamin A control programs.  We have therefore proposed to conduct this validation study in rural Zambian children in whom the prevalence of vitamin A deficiency is estimated at 54%.

Goal

Hence the overall goal of the proposed study is to quantify the extent of malaria-induced hyporetinolemia and to validate the icheckTM for assessment of vitamin A status in at-risk populations. Specific aims and hypotheses are as follows:

AIM 1: To quantify the  effect of malaria-induced inflammation on estimates of vitamin A status.

• Hypothesis 1a:  retinol levels will be lower in children with malaria-induced inflammation(MIn).
• Hypothesis 1b: the prevalence of VAD will be elevated by malaria-induced inflammation(MIn).

AIM2: To Validate the icheckTM against the conventional HPLC method for the determination of vitamin A status.

• Hypotheses 2: We expect the icheckTM  to be a sensitive and specific predictor of VA status. We also expect estimates of retinol levels from the icheckTM to correlate highly and significantly with the  HPLC approach for plasma retinol.

Method

Setting: Data collection shall occur at 5 rural health centers and one district hospital in Nchelenge, Zambia. Childhood malaria and VAD in this population is estimated at 30% and 54% respectively.

Study type and size:  longitudinal study involving data collection at two time points separated 6 months apart.  Study shall involve children 6-59 months. To address aim1, we shall use  870 children. We shall be able to detect a reduction in retinol levels of 0.26umol/L  and an increase in VAD of 20% with 80% power and 5% type 1 error rate. To address aim 2, we shall use a random sample of 200 children used in aim 1. Children presenting for the semi-annual child health week(CHW) shall be recruited.

Data collection and laboratory analyses: For all children, dried blood spots(DBS) shall be prepared using finger-pricked blood at baseline and during follow-up( 6 months later) to determine the levels of CRP, AGP and retinol. We shall also collect malariometric data including fever and RDT at baseline and during follow-up. For the validation study, about 300ul of capillary blood shall be collected from a sub-sample of 200 children to perform the icheckTM and HPLC. We shall use enzyme-linked immunoassay (ELISA) to  determine the levels of CRP and AGP. DBS retinol levels shall be analyzed using HPLC.

Outcomes and Exposure: For aim 1, our outcome of interest is the transient change in retinol attributable to malaria-induced inflammation. Outcomes for aim2(validation study) include the sensitivity, specificity, predictive values and Pearson correlation coefficient comparing results of the icheckTM  against  plasma retinol levels obtained using reverse phase HPLC. Our primary exposure of interest is  malaria-induced inflammation(MIn) defined as a positive malaria RDT PLUS fever (axillary temperature >37.5°C) in the absence of other febrile illnesses PLUS an elevated CRP(>10mg/L) or elevated (>0.8g/L).

Analysis: For aim 1, we shall limit the analyses to children who transitions between a state of MIn and a state of no MIn  over the two observation times. Thus we shall limit the analyses to children who had MIn at baseline but not at follow-up and those who had MIn at follow-up but not at baseline. We shall use generalized estimation equations (GEE) to estimate the effect of MIn on retinol status. We shall use GEE with logit link function to estimate the effect of MIn on the prevalence of VAD. We shall estimate the sensitivity, specificity, predictive values and Pearson correlation coefficient comparing results of the  icheckTM  against  plasma retinol levels obtained using reverse phase HPLC. Control for potential confounders shall be determined by prior exploratory data analyses.  Statistical significance shall be set at p=0.05.

Significance

This is the first attempt to quantify the strength of  malaria-induced hyporetinolemia using a prospective design. Failure to address this issue will inevitably result in overestimation of the burden of VAD and may lead to wasteful allocation of limited resources. The proposed study is also the first attempt to validate the icheckTM in an African setting where the burden of VAD is greatest. It is estimated that about 140-250 million children may be vitamin A deficient globally. The huge uncertainty in the  estimates of the actual burden of VAD is in part attributable to lack of low cost,  feasible tools for routine  assessment in the regions most affected. For instance in Zambia the current estimate of VAD in children is based on a  survey conducted in 2003. Without routine assessment of vitamin A status, it is impossible to  empirically demonstrate the impact of existing vitamin A control program.

Results from this study may lead to revision of previous estimates of VAD in low income countries and may also shape the design of future studies aimed at estimating the burden of VAD. The validation study may lead to a new paradigm in which population based vitamin A assessment is conducted more frequently to guide allocation of limited resources. Overall, the study has practical implications for integrated malaria-vitamin A control programs particularly in Sub-Saharan Africa. Guided malaria and vitamin A control is critical in reducing the burden  of morbidity and mortality in children.

Itemized Budget

Alison Connor, PhD Student
Uterotonic Use and Its Maternal and Perinatal Health Impact in Sarlahi, Nepal

Introduction

The goal of this study is to gain a better understanding of current practices regarding the use of uterotonics during home deliveries and their subsequent impact on the health and well-being of mothers and newborns in rural, southern Nepal. Effective uterotonics, agents such as oxytocin and misoprostol that are used to induce or speed up labor as well as to stop bleeding after delivery, have been used to ease labor and delivery and to prevent or mitigate complications for decades. When used inappropriately, however, these same uterotonics can have serious adverse effects. Home use of uterotonics before the baby is born where skilled provision and proper monitoring of danger signs are lacking is thought to be unsafe for both mothers and newborns. In low-income countries like Nepal, injectable uterotonics are widely available without a prescription or instruction on proper use.

Between August 2002 and January 2006, a placebo-based randomized controlled trial of both newborn skin cleansing and umbilical cord cleansing with chlorohexidine was completed and subsequently scaled-up in Sarlahi District, Nepal. As part of the data collection process, women were visited as soon after delivery as possible to assess the health status of the mother and infant, as well as to gather information about the delivery process. At this time, women were asked, “Was anything done to help the baby come out” to which they could provide up to three responses. Of the 22,352 live births for which there were data, 7,108 (31.8%) mothers reported receiving an injection. This study was not, however, designed to evaluate these outcomes.

This study has six primary aims: 1) To describe and to quantify the use of uterotonics in southern Nepal, including the demographic and health characteristics of the women who receive them, the reason for use, as well as the characteristics and identity of the uterotonics themselves; 2) To estimate the incidence of inappropriate use of uterotonics; 3) To evaluate the association of demographic, maternal health, and delivery characteristics with the inappropriate use of uterotonics during labor and delivery among women in southern Nepal; 4) To determine if inappropriate use of uterotonics increases the risk of postpartum hemorrhage by 20% (RR of 1.20 or greater) among women in southern Nepal compared to those who do not inappropriately use uterotonics; 5) To determine if inappropriate use of uterotonics increases the risk of fresh stillbirth by 90% (RR of 1.9 or greater) among perinates in southern Nepal compared to those who do not inappropriately use uterotonics; 6) To determine if inappropriate use of uterotonics increases the risk of intrapartum-related perinatal respiratory depression and neonatal encephalopathy during the first week of life by 40% (RR of 1.4 or greater) among neonates in southern Nepal compared to those who do not inappropriately use uterotonics.

Methods

This is a community-based, prospective cohort study that will be nested within three concurrent large-scale, community-based randomized controlled trials in Sarlahi Nepal which use similar data collection methods. It will follow a cohort of pregnant women identified mid-pregnancy until labor and delivery. Live-born infants will be followed one week until the end of the early neonatal period. All women enrolled in any of the three parent trials will be eligible for this study.

Women will be enrolled during mid-pregnancy at which time information about the woman’s household characteristics and health and reproductive history will be collected. The women will be followed until labor and delivery. Data collectors will visit the woman as soon after the delivery as possible to collect information about the course of the delivery and whether or not she received any uterotonics. If a uterotonic was administered, additional information will be collected around who administered it, how much was administered, during which stage of labor this occurred, and what the woman suspects the identity of the uterotonic to be to distinguish appropriate from inappropriate uterotonic use.

The specific maternal health outcome that will be assessed will be postpartum hemorrhage. This will be measured by providing women pads and cloth with which to collect blood immediately after delivery. These materials will be weighed by the data collector as soon after delivery as possible. This weight will be subtracted from the materials’ pre-delivery weight to calculate the amount of blood loss based on the pre-determined density of blood. The specific perinatal health outcomes that will be assessed are fresh stillbirth, intrapartum-related perinatal respiratory depression, and early neonatal encephalopathy. Fresh stillbirth will be measured by asking questions about the appearance of a stillborn infant to distinguish between macerated and fresh stillbirth. Intrapartum-related perinatal respiratory depression and early neonatal encephalopathy will employ sign-based algorithms.

The necessary sample size was calculated using a difference in proportions between unequal groups. The postpartum hemorrhage outcome will drive the sample size needs. In this setting, it is estimated that the background rate is 0.15. Current literature suggests that women who inappropriately use uterotonics may have a 20% greater risk of postpartum hemorrhage than those who do not use them inappropriately (RR=1.2). Using a 0.05 (two-sided) level of significance and 0.90 power, an assumed 10% loss to follow-up and a ratio of groups equal to 3, the required sample size would be 2,383 women receiving uterotonics inappropriately, 7,149 women not receiving uterotonics inappropriately for a total enrollment of 9,532

Significance

In Nepal, 81% of deliveries take place at home where skilled attendants and basic care are often lacking.  Thus, the majority of births take place in an unmonitored, uncontrolled environment. Synthetic uterotonics such as oxytocin are readily available in the community and the Ministry of Health is piloting the use of oral misoprostol for prevention of postpartum hemorrhage, the leading cause of maternal death globally. Without proper monitoring of current practices, however, increased access to these drugs may prove harmful to both the mother and the infant. To date, no published study has prospectively looked at the association of uterotonic use during home deliveries with adverse maternal or neonatal outcomes. This knowledge will help inform future interventions and policies to improve maternal and perinatal health as a result of safer labor and delivery by identifying positive deviants and potential avenues by which to increase the benefits of appropriate uterotonic use during labor and delivery as well as knowledge gaps, inappropriate and harmful practices, and associated health outcomes.

Allocation of expenses by category up to $1000.00