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2010 DELTA OMEGA POSTER COMPETITION ABSTRACTS

Poster Number    1     Applicant Name    Haley Hedlin      
Project Title    Covariate-adjusted Nonparametric Analysis of Magnetic Resonance Images using Markov Chain Monte Carlo      
Descriptive Abstract Summary    Introduction: Permutation tests are useful for drawing inferences from imaging data because of their flexibility and ability to capture features of the brain under minimal assumptions. However, most implementations of permutation tests ignore important confounding covariates. To employ covariate control in a nonparametric setting we have developed a Markov chain Monte Carlo (MCMC) algorithm for conditional permutation testing using propensity scores. We present the first use of this methodology for imaging data. Our MCMC algorithm is an extension of algorithms developed to approximate exact conditional probabilities in contingency tables, logit, and log-linear models. An application of our nonparametric method to remove potential bias due to the observed covariates is presented.

Methods:  We applied the algorithm to a dataset consisting of 161 right-handed subjects between the ages of 48 and 83. 85 are at-risk for late-onset Alzheimer’s disease, 66 of the subjects are male and 75 have at least one !4 allele of the apolipoprotein E (APOE) gene, a gene whose presence is linked with the risk of Alzheimer’s disease. Each image is a 79x95x68 array of 2 mm3 voxels obtained as contrast estimates from a verbal paired word paradigm. A Gaussian smoother was passed over the images with a 5 mm full width at half maximum kernel. Differences between the two groups are hypothesized to exist in the medial temporal lobe; hence, the imaging area was restricted. To detect volumetric differences between the at-risk and control groups while controlling for gender and the number of !4 alleles of the APOE gene, we permute the at-risk and control labels on the images while preserving the gender and APOE status associated with each image. In most datasets the number of possible permutations is too large to be enumerated so we use a MCMC algorithm to ensure we appropriately represent the null distribution.
Each iteration in the chain results in a permutation. Because the computational burden associated with each iteration is much less than the cost of calculating the test statistic at each permutation, we subsampled the Markov chain. A z-map was created at each remaining!Submitting student: H. Hedlin, Advisor: B. Caffo 1 permutation and the null distribution of the test statistic was formed from the set of all permutations. We chose to use the maximum cluster size in this application; however, the flexibility of permutation testing allows a choice of test statistics.

Results: We ran the MCMC algorithm for 1.1!109 iterations, discarded the first 1.0!108 and kept every 1.0 ! 106 iterations after the burn-in. 1,000 iterations remain to form the null distribution. In the original dataset there were two significant clusters of voxels, one containing 4 voxels and the other containing 5 voxels. Hence, the maximum cluster size is 5 voxels. From the null distribution generated by the MCMC algorithm we calculate that the probability of observing data as or more extreme than the example data to be 0.330 under the hypothesis of no difference between the two groups.

Conclusions: We have introduced a novel and flexible method for covariate control in neuroimaging studies. This nonparametric method permutes the group labels conditionally on the covariates using an algorithm supported by theory developed for MCMC and exact conditional tests. The example presented is intended for exploratory purposes to guide future research, but the method is not limited to this purpose.     
 
Poster Number    2      
Applicant Name    Lisa Wyman      
Project Title    Glycemia and Depression: The Atherosclerosis Risk in Communities Study      
Descriptive Abstract Summary    Background: Previous studies have shown a robust association between depression and risk of type 2 diabetes. Hyperglycemia is the defining feature of diabetes, but the relationship between glycemia and depression prior to the diagnosis of diabetes is not well characterized. We undertook this study to examine the association between average levels glycemia—as assessed by hemoglobin A1c (HbA1c)—and depressive symptoms in persons without diagnosed diabetes. We hypothesized that HbA1c would be positively and independently associated with depressive symptoms in individuals without diabetes.
Methods and Design: We analyzed data from 12,353 middle-aged adults without a history of diabetes who participated in the Atherosclerosis Risk in Communities (ARIC) Study. Self-reported depressive symptoms were measured using the 21-item Vital Exhaustion Questionnaire (VEQ). HbA1c was measured from stored whole blood samples.  We used logistic regression to model the association between HbA1c levels (continuous and using clinically relevant cut-points) and the highest quartile (Q4) of VEQ score (vs Q1-Q3) before and after adjustment for relevant confounding variables.
Results: We observed a significant positive and roughly linear association between HbA1c categories and depressive symptoms in unadjusted and minimally adjusted models. The odds ratios for HbA1c <5.0, 5.0-<5.5, 5.5-<6.0, 6.0-<6.5, ?6.5% and elevated depressive symptoms (VEQ Q4 vs Q1-Q3) were 0.93, 1.0 (reference), 1.23, 1.36, and 1.66, respectively. However, this association was not significant after adjustment for potential confounding variables (see Table). Adjustment for demographic, metabolic, and behavioral factors completely explained the observed association (adjusted OR 0.99, 0.91 to 1.06).

Conclusions: Our results suggest the relationship between glycemia and elevated depressive symptoms can be primarily explained by demographic, metabolic and behavioral factors, particularly adiposity, activity levels, and caloric intake. These findings suggest possible mechanisms by which depression enhances the risk of diabetes.

Odds ratios (95% CIs) of HbA1c (per 1-% point) and presence of elevated depressive symptoms, 12,353 middle-aged adults without a history of diabetes, the Atherosclerosis Risk in Communities (ARIC) Study, 1990-1992
 

Model    Outcome: Presence of elevated  depressive symptoms   
% excess odds explained      
     OR    95% CI           
    1.22    1.15-1.30          
Model 1    1.16    1.09-1.23    27%      
Model 2     1.06    0.99-1.13    73%      
Model 3     1.05    0.98-1.12    77%      
Model 4     0.99    0.91-1.06    ~100%      
Model 1: age, sex, race, center
Model 2: + body mass index, waist-hip-ratio, physical activity level, caloric intake
Model 3: + fasting LDL- and HDL-cholesterol levels, triglycerides, hypertension status
Model 4: + smoking status, alcohol intake, education level, income
Abbreviation: VEQ, Vital Exhaustion Questionnaire     
     
 
Poster Number    3      
Applicant Name    Kristina Das      
Project Title    Reintegration of ExOffenders: An Innovative Approach to Community Outreach and Human Resources at the Johns Hopkins Hospital.   -                   
Descriptive Abstract Summary    Motivation: While healthcare management is a complex business, one area that is overlooked is community outreach and the important role hospitals play in the community. It is not enough to merely medically serve the people of its community; but even more, hospitals have a social responsibility to give back to the community and must also make efforts to constantly benefit and improve the community to which it belongs. Further, in light of the many ethical issues that large corporations have faced in the past decade, many companies are making greater efforts to align their mission, vision, and values with their service. The Johns Hopkins Hospital has long realized this responsibility in serving its community, first and foremost, despite its global presence and prestige.
Often times, large teaching hospitals, like The Johns Hopkins Hospital, are located in low income cities with high crime rates. It is a well known fact that one of the greatest obstacles for many ex-offenders is finding employment with a blemished record. This lack of employment can often lead ex-offenders back into criminal activity, and thus perpetuates the cycle of crime. Studies have shown that many offenders are likely to end up in a correctional facility within one year of release. Furthermore, recent research emphasizes the importance of pre and post-release support in reducing offender recidivism.
East Baltimore, the city in which The Johns Hopkins Hospital is located, is stigmatized as having one of the highest crime rates in the United States. Rather than turning a blind eye to the problems faced by the city, The Johns Hopkins Hospital, envisioned a plan to combine The Johns Hopkins Hospital hiring practices to an initiative to facilitate integration of ex-offenders into society through employment opportunities   within the hospital.
Problem/Approach: The following paper analyzes the retention rates of hired ex-offenders with the retention rates of hired non-ex-offenders during the same period. Data has been gathered for 2003, 2004, 2005, and 2006 on ex-offenders and non-ex-offenders that were hired in those years. The method of analysis used for this project is the Kaplan-Meier Estimator, Cox Regression and Log Rank Test.
Results: The initial analysis of this study shows that the retention rate of ex-offenders is comparable to that of non-ex-offenders, and has actually shown that ex-offenders are less likely than non-ex-offenders to be terminated. The Cox Regression Test shows that the Hazard Ratio is .9160904 [CI: .8046192, 1.043005]. The Hazard Ratio (also known as relative risk) can be interpreted as the ratio of the rates of the two populations, here as ex-offenders and non-ex-offenders. Since the Hazard Ratio is calculated as less than or equal to 1, meaning that involuntary termination is no more likely to occur in ex-offenders than non-ex-offenders. Additionally, because the calculated Hazard Ratio is actually less than 1, and thus ex-offenders are actually less likely to be terminated than non-ex-offenders.
Conclusions: Given the comparable retention rates of the two groups, it is evident that hiring of these ex-offenders has been a beneficial step in the very least. By accounting that many are still employed shows that these ex-offenders have in fact stayed out of the correctional facilities. Although this study lacks the scope of evidence to show that this program has lowered the recidivism rate of the city, it does imply that current employment has kept them out of prison. The study has further implications in the realm of human resources. The similar retention rates of the two groups shows that ex-offenders are no less likely than non-ex-offenders to leave. Therefore, specifically for the institution there seems to be no greater “danger” of job abandonment in ex-offenders than for the normal population. Broader implications of this study may help to decrease the stigma associated with the hiring of ex-offenders, and possibly the introduction of this practice at other hospitals and organizations. Further studies may include comparisons of rates of promotion, types of offenses, and reasons for termination, if terminated.     
 
Poster Number    4      
Applicant Name    Kristin Gibson      
Project Title    Tangential Flow Ultrafiltration and Molecular Detection of Surrogates and Pathogens in Large-Volume Environmental Water Samples      
Descriptive Abstract Summary    Accurate and comprehensive assessments of microbial water quality are vital if both existing and new drinking water sources are to be safely employed. Water quality issues are of increasing importance due to increasing negative environmental impacts on current water supplies. These impacts can affect the development of alternative water sources. Emerging human and animal microbial pathogens associated with waterborne transmission are of particular concern to the public health community. A major limiting factor in evaluating the microbial quality of various water sources is the lack of an effective and efficient method for simultaneous collection and recovery of low levels of bacteria, viruses, and protozoa and the subsequent inability of these isolated microbes to be rapidly identified and quantified. Current methods for the assessment of microorganisms in water are targeted towards specific pathogen groups.

This research aimed to address some of the inadequacies of the current methods and standards used for evaluating microbial water quality within drinking water systems and source waters. The goals were to optimize and implement tangential flow ultrafiltration (UF) technology for the simultaneous recovery of low levels of bacteria, viruses, and protozoa from large-volume water samples; to evaluate quantitative polymerase chain reaction (qPCR) for the detection of select enteric pathogens; and to apply these methods to large-volume environmental water samples for the detection and quantification of microbial contaminants.

A UF method was optimized to simultaneously concentrate and recover each class of microorganism from 100L water samples. Filter type, surfactant addition, and elution steps were evaluated during UF optimization. For these evaluations, microbial surrogates including E. coli CN-13, E. faecalis, C. perfringens spores, MS2 and PRD1 bacteriophages, poliovirus and murine norovirus (MNV-1) were added to either dechlorinated tap water (DW) or surface water (SW). During UF, 100L water samples were recirculated using a peristaltic pump at 1,700 mL/min through commercially available capsule filters containing hollow fiber membranes with an average molecular weight cut off  (MWCO) of 70,000 daltons and a total surface area of 2.1m2. This initial filtration concentrated the water sample 86-1,250 fold.  The ultrafilter concentrate (80 to 1,200 mL) was portioned into three aliquots for further microbial-specific processing. A portion of these aliquots was further concentrated using a Centricon Plus-70 (100kDa MWCO) centrifugal filtration unit to provide an additional concentration of 35-350 fold. The secondary concentrate was then analyzed for infective virus particles and viable bacterial cells and spores. For viral analysis, an additional 200ml of the secondary concentrate was processed using QIAamp® MinElute® Virus Spin kit for total viral nucleic acid (NA) extraction and removal of potential PCR inhibitors. This extracted NA was analyzed for target NA by quantitative reverse transcription PCR (qRT-PCR).

Recovery efficiency was assessed via standard culture methods and/or qRT-PCR. The following culture methods were used for analysis of microbial surrogates: IDEXX Quanti-tray® system (E. coli  CN-13 and E. faecalis); spread plate on mCP agar (C. perfringens bacterial spores); Double Agar Layer method using E.coli Famp and S. typhimurium bacterial hosts (MS2 and PRD1 bacteriophages, respectively); and plaque assay using RAW 264.7 cells and BGM-K cells (MNV-1 and poliovirus, respectively). UF concentrates were also analyzed for MNV-1 RNA by qRT-PCR. For viral RNA amplification, QuantiTect Probe RT-PCR Kit was used. An ABI Prism 7300 Sequence Detection System was used for target NA amplification in a total reaction volume of 25µl (5µl of prepared sample added to 20 µl master mix). Positive and negative control samples were analyzed with each thermocycler run to ensure reagent and cycling efficiency. Each qRT-PCR sample assay incorporated an internal standard using Hepatitis G RNA to identify potential sample inhibition. Sample inhibition occurred if the sample hepatitis G RNA threshold cycle (Ct) value deviated from the average Ct value of the positive control (PC) Hepatitis G RNA by one Ct value.

During optimization of the UF method, 100L water samples were seeded with a total of 104 to 106 plaque forming units (PFU) or colony forming units (CFU) of target microorganisms. Using standard culture techniques listed above, the average recovery efficiencies for vegetative bacteria, viruses, and bacterial spores in DW (n=25) were 75, 50, and 59% and in SW (n=5) were 62, 49, and 30%, respectively. In addition, target MNV-1 was detected in all DW concentrates (n=15) and 4 of 5 spiked SW sample concentrates tested. The recovery efficiency demonstrates the ability of the UF system to simultaneously concentrate bacteria, viruses, and spores from large volume lab-based water samples and allow for detection via standard culture methods and molecular assays.

Following optimization, UF was then applied to 100L surface water (SW) and ground water (GW) samples collected from the Lower Yakima Valley, WA—a region with the densest concentration of dairy operations and milk cows in WA and with known nitrate contamination in GW sources. The study area comprised a 49-mile corridor between the cities of Prosser and Yakima where there are approximately 79 dairy operations. One hundred liter GW (n=10) and SW (n=11) UF sample concentrates were evaluated for total coliforms, E. coli, and Enterococcus spp. using the IDEXX® detection system. A portion of the UF concentrates were then further concentrated and total NA extracted as described above. Grab samples of the GW (i.e. before concentration with UF), revealed that 3 GW sites were positive for the presence of total coliforms, and none were positive for either E. coli or Enterococcus spp. Following UF concentration, total coliforms and Enterococcus spp. were present in 9 and 4 GW UF concentrates, respectively. No E. coli were present in GW UF concentrates. All SW samples were positive for the presence of total coliforms, E.coli, and Enterococcus spp. before and after concentration with UF with average recovery efficiencies of 77, 70, and 143%, respectively. In addition, to evaluate viral recovery, each 100L sample was spiked with a total of 106 MNV-1 PFU and analyzed by plaque assay and qRT-PCR. A Hepatitis G RNA internal standard was incorporated in these qRT-PCR assays to identify potential sample inhibition.  MNV-1 was detected in 8 of 10 GW UF concentrates by plaque assay. MNV-1 RNA was detected in all processed GW (n=10) and 9 of 11 SW UF concentrates via qRT-PCR. Additional viral and protozoa analysis are ongoing and include analysis for the presence of bovine enteroviruses and bovine noroviruses as well as Cryptosporidium and Microsporidia.

This study demonstrates the effectiveness of using a UF method for microbial evaluation of 100L environmental water samples. By developing a universal method for the recovery of microorganisms, water utilities and regulatory agencies will be better equipped to address microbial threats within public water systems. In addition, a more comprehensive understanding of the microbial contamination of various water sources is now possible. Overall, this research will assist in the formulation of effective control measures for the reduction of water-related transmission of pathogenic microorganisms.     
 
Poster Number    5      
Applicant Name    Russell Shinohara      
Project Title    Estimating effects by combining instrumental variables with case-control designs      
Descriptive Abstract Summary    Many scientific studies seek to estimate the causal effect of an exposure E on an outcome Y. Although experimentation with E is the most reliable design for making causal claims, there is a plethora of situations in which it is either impossible or unfeasible. To address this, it is often useful to combine designs.
An example of such a combined design is involved in the CLUE II study (e.g., see Erlinger et al.  2004), a prospective cohort follow-up of serological risk factors for cancer and heart disease. The subjects were sampled as a large cohort from communities in Maryland between 1989 and 2000. The scientific target here is the effect that chronic low-grade inflammation has on the risk of colorectal cancer. Inflammation is measured via C-reactive protein (CRP) concentrations in archived baseline blood samples. For reasons common to many such studies, two designs are employed simultaneously.

First, the cost of measuring some variables made it infeasible to record all such information for each member of the cohort. A nested case-control design was thus employed. All 172 cases of colorectal cancer were sampled and 342 matched controls were selected based on age, sex, and date of blood draw.

Secondly, the mechanisms of inflammation are not fully known. For this reason we also use the genotype G of each member of the case-control study for a given SNP called rs1205 that is known to stimulate inflammatory processes (Carlson et al., 2005), because the variation in G is well understood and stems from meiosis and fertilization. Details on the genotyping and SNP selection process have been published elsewhere  (Tsilidis et al., 2009). In the more general literature, such genetic variables are also known as Mendelian randomizers (see Didelez and Sheehan, 2007, or Davey Smith and Ebrahim, 2003, for an extensive review). The above design therefore combines case-control and Mendelian randomization. 
We show that the methodology of standard instrumental variables is not directly applicable to estimate general causal effects based on potential outcomes, when Mendelian randomization is combined with case-control designs. This is because case-control data alone do not include any information about the prevalence or incidence of disease in the population (our points apply when either prevalence or incidence over a time period, as in the colorectal cancer study, is involved). We demonstrate that in order to identify the causal effects of interest, the data require supplementation with the incidence of cancer. This result is important when contrasted with the classical estimation of odds ratios of association, where such incidence information is ancillary (Prentice and Pike, 1979). Specifically, one can estimate those odds ratios by simply conditioning on the exposure. In the combined case-control Mendelian randomization, however, the incidence plays a crucial role.

We also show how to address this problem. First, as the incidence information is not available from the case-control study alone, it must be obtained externally. Such information is often readily available from prior studies directly or through databases such as the Surveillance Epidemiology and End Results Program which lists the estimated incidence of cancer in the United States. This information must be combined with the observed case-control data in order for proper analysis to be conducted. We show that this can be accomplished through the use of principal stratification (Frangakis and Rubin, 2002), a framework which generalized the work of Angrist, Imbens, and Rubin (1996) for instrumental variables in broader settings.     
 
Poster Number    6      
Applicant Name    Judy Choi      
Project Title    Functional role of the neurotoxicity biomarker protein TSPO/PBR in primary microglia.      
Descriptive Abstract Summary    Translocator protein-18 kDa (TSPO), previously called the peripheral benzodiazepine receptor (PBR), is a glia protein that has been extensively used as a biomarker of brain injury in a variety of animals models of neurotoxicity and in human neurodegenerative disease (Chen&Guilarte, Pharm Ther 118:1-17,2008). While TSPO is a validated biomarker of neurotoxicity, the functional role of TSPO in glial cells is not known. In this study, we examine the effect of TSPO activation by the TSPO-specific ligands RPK11195 (PK) and Ro5-4864 (Ro) in primary microglia. Exposure to different concentrations (1-1000 nM) of PK for 24 hrs resulted in increased production of intracellular reactive oxygen species and increased microglia proliferation and phagocytosis. No effect on intracellular levels of reactive nitrogen species was measured. A similar effect was observed with Ro. These ligands did not affect microglia migration, but PK produced mitochondria hyperpolarization while Ro did not. We also examine whether these ligands could alter expression of pro-inflammatory genes and cytokine release in lipopolysaccharide (LPS)-activated microglia. At a 10 nM concentration, neither PK nor Ro had an effect on LPS-induced increase in COX-2, IL- 1?, or TNF-? gene expression. Ro but not PK did enhance the LPS-induced release of IL-1?. Consistent with this finding, Ro but not PK increased the number of apoptotic microglia. These studies showed that TSPO activation regulates cellular processes that are essential to microglia function. Further, when microglia are activated by an inflammogen, TSPO activation enhances IL-1? release and increases microglia apoptosis. These findings suggest that TSPO plays a critical role in cellular functions that are essential to mount a microglia response to the disruption of brain homeostasis. They also indicate that under pathological conditions, TSPO activation may be responsible for the elimination of activated microglia via apoptosis. [Supported by NIEHS-ES07062 to TRG and NIEHS-T32 ES07141]     
 
Poster Number    7      
Applicant Name    Sivabalan Manivannan      
Project Title    AMPA receptors are present on mouse lymphocytes and AMPA receptor antagonist, GYKI-52466, inhibits lymphocyte proliferation.       
Descriptive Abstract Summary    AMPA receptors are glutamate-gated ion channels canonically found on mammalian neurons for excitatory neurotransmission.  AMPA receptors are composed of a tetrameric combination of subunits, GluR1-4, in the form of a homo or hetero dimers.  The presence of a post-transcriptionally edited GluR2 subunit confers Ca++ impermeability to the ion channel.  Because treatment of mice with viral encephalitis with AMPA receptor antagonists inhibits inflammation and protects from fatal paralysis, we studied the presence and function of AMPA receptors on lymphocytes.  Using RT-PCR and restriction digest assays of mRNAs obtained from mouse spleen cells, we showed the presence of unedited mRNA for Ca++-permeable GluR2 and for variants with alternative splicing patterns. Using an in vitro CFSE proliferation assay with plate bound anti-CD3/CD28 we showed that the noncompetitive AMPA receptor antagonist, GYKI-52466, suppresses T-cell receptor CD3+ lymphocyte proliferation in a dose dependent manner, with the greatest effect on CD4+ T cells.  Decreased proliferation correlated with decreased production of IL-2.   Lymphocytes treated with GYKI-52466 did not show an increase in cell death compared to controls.  These studies show that AMPA receptors are present on lymphocytes and participate in the proliferative response to signaling through the T-cell receptor.          
 
Poster Number    8      
Applicant Name    Su Yeon Lee      
Project Title    Prevalence of Depression, Cognitive Impairment and Mental Health Service Utilization among community-residing Korean Elders: Preliminary Findings from the Memory and Aging Study among Koreans in Maryland (MASK-MD)      
Descriptive Abstract Summary    Introduction: While the number of Asian-Americans 65 year and older is expected to triple by 2030, little is known about their mental health needs and pattern of mental health service utilization. Estimated nearly two million in U.S., Korean-Americans comprise the fourth largest Asian-American subgroup, and the vast majority (up to 85%) of Korean elders attends ethnic churches. The Memory and Aging Study among Koreans in Maryland (MASK-MD) is a community-based, cross-sectional study that examines mental health service needs of Korean elders while establishing partnership with Korean churches to develop strategies to improve their mental health.

Methods: Based on cluster sampling method, we selected twenty out of one hundred fifty Korean churches in Baltimore-Washington area and recruited 631 Korean American elders (mean age: 71.03 +/- 6.31 years; female: 69.5%), all were first-generation immigrants. Participants were screened for depression and dementia based on Korean versions of Patient Health Questionnaire (PHQ-9-K) and Mini-mental Status Examination (MMSE-KC) administered face-to-face by trained community health workers.

Results: 22.8% and 7.2% of the participants had PHQ-9 scores of 5 or above ("any depression") and 10 or above ("clinical depression"), respectively. 19.2% scored less than 24 on MMSE-KC, and 7.0% scored below the age- and education-specific cut-off values for “probable dementia” based on Korean normative data for MMSE-KC. Of forty-five participants screened positive for severe depression (PHQ>=10), only eight (18.2%; all females) reported seeking treatment from a health care provider and one of them was on antidepressant. Likewise, of forty-one participants with “probable dementia” based on Korean MMSE-KC normative data, only three (7.3%) sought consultation and treatment from a health care provider.

Conclusions: The prevalence of depression and cognitive impairment are high in this sample of community dwelling Korean American elders. Rate of mental health service utilization among depressed or cognitively impaired Korean elders, especially men, is low. Further research is needed to further identify barriers to and strategies for adequate mental health care for Korean immigrant elders.

Table 1. Prevalence of depressive symptoms, cognitive impairment, and mental health utilization
 
     Male (n=193)    Female (n=440)         Total (N=633)      
     Mean (SD)    Mean (SD)    P-value    Mean (SD)      
Age    71.45(5.69)    70.84 (6.14)    NS    71.03      
Education    7.24 (2.52)    4.97 (5.26)    <0.001    5.67 (4.11)      
# Medication    2.35 (1.96)    3.11 (2.23)    <0.001    2.88 (2.15      
PHQ-9 score    2.27 (2.60)    3.48 (4.05)    <0.001    3.11 (3.80)      
MMSE    26.84 (2.59)    25.54 (3.62)    <0.001    25.97 (3.40)      
     N (%)    N (%)         N (%)      
PHQ-9 score >= 5    28 (14.6)    115 (26.4)    0.001    143 (22.6)      
PHQ-9 score >= 10    11 (5.7)    34 (7.8)    NS    45 (7.4)      
Saw Health Service Provider    5 (2.6)    24 (5.5)    NS    29 (4.6)      
On Antidepressant    0 (0)    7 (1.6)    NS    7 (1.1)      
On Benzodiazepine    2 (1.0)    6 (1.4)    NS    8 (1.3)      
MMSE below 24    21 (10.9)    100 (23.0)    0.001    121 (19.3)      
MMSE below cutoff    11 (5.7)    30 (6.9)    NS    41 (6.5)      
Saw health service provider    6 (3.1)    5 (1.1)    NS    11 (1.8)      
On cognitive enhancer    2 (1.0)    3 (0.7)    NS    5 (0.8)     


Table 2. Utilization of mental health services among depressed or cognitively impaired
 
Sought help from health service provider for mood    On antidepressant    On benzodiazepine       
          N    %    N    %    N    %      
PHQ>=5    Total (n=142)    18    12.7    5    3.5    6    4.2      
     Male (n=28)    0    0    0    0.0    1    3.6      
     Female (n=144)    18    14.2    5    4.3    5    4.3      
PHQ>=10    Total (n=45)    8    17.8    1    2.2    4    8.9      
     Male (n=9)    0    0    0    0.0    1    11.1      
     Female (n=36)    11    30.6    1    2.8    3    8.3      
Sought help from health service provider for cognition    On cognitive enhancer                 
          N    %    N    %                
MMSE below cutoff    Total (n=41)    3    7.3    2    4.9                
     Male (n=11)    1    9.1    1    9.1                
     Female (n=30)    2    6.7    1    3.3               
     
 
Poster Number    9      
Applicant Name    Miranda Jones      
Project Title    Acute Coronary Events Following Enactment of Smoke-Free Legislations:  A Systematic Review and Meta-analysis      
Descriptive Abstract Summary    Context: Secondhand tobacco smoke is a risk factor for cardiovascular disease. To protect the population from exposure to secondhand smoke, governments worldwide are implementing legislations banning smoking in indoor public places and worksites. Several studies have reported reductions in hospitalizations for acute coronary events following the enactment of comprehensive smoke-free legislations.

Objective: To systematically review and summarize the evidence available on the impact of legislations that ban smoking in all public settings and workplaces, including restaurants and bars, on subsequent population risk for acute coronary events.

Methods: We searched MEDLINE, EMBASE, and relevant bibliography for ecological studies that evaluated hospitalizations for acute coronary events, including myocardial infarction, pre- and post-implementation of smoke-free legislations. Studies were identified through July 2009. Relative risk (RR) estimates for acute coronary events post- vs. pre-legislation were pooled using inverse-variance weighted random-effects models.

Results: Of 1,078 studies identified, 11 met the inclusion criteria (7 were conducted in North America and 4 in Europe). Legislations were implemented between 2002 and 2006. Pre-legislation follow-up ranged from 12 to 48 months. Post-legislation follow-up ranged from 3 to 39 months. Seven studies assessed hospitalizations for acute myocardial infarction (ICD-9 410) and 4 for acute coronary disease (ICD-9 410-414, 428). Overall, the enactment of comprehensive smoke-free legislations was associated with a 25% reduction in hospitalizations for acute coronary events (pooled RR: 0.75, 95% CI: 0.69-0.81). Reductions were larger in studies from North America (RR 0.63, 95% CI: 0.52-0.76) compared to studies conducted in Europe (RR 0.91, 95% CI 0.82-1.01). Reductions in acute coronary events were similar by gender (RR: 0.80 for men and 0.86 for women). In studies that evaluated differences by age, reductions were generally smaller in older compared to younger age groups. Only two studies stratified by smoking status, with reductions in coronary events occurring both in never and ever smokers.

Conclusion: The implementation of comprehensive smoke-free legislations was consistently associated with short-term reductions in hospitalizations for acute coronary events. Further research is needed to evaluate long-term benefits of smoke-free initiatives in reducing the burden of cardiovascular disease morbidity and mortality. Meanwhile, these short-term cardiovascular benefits provide additional support to the urgent need to implement worldwide smoke-free legislations that protect the population from indoor exposure to tobacco smoke.     
 
Poster Number    10      
Applicant Name    Yayi Guo      
Project Title    A Comparative Analysis of the Microorganism Removal Capabilities of Potters for Peace Ceramic Filtration Devices Manufactured in Different Countries      
Descriptive Abstract Summary    Over 850 million people do not have access to improved drinking water. In areas where treated, piped water systems are not available, point-of-use ceramic water filters (CWFs) may provide safe drinking water to individual households. One internationally promoted treatment system is a pot-shaped CWF adopted by the Potters for Peace (PfP) organization. However, differences in manufacturing practices may result in variable microorganism removal. To assess microbial removal capabilities, PfP CWFs imported from Honduras (n=24) and Nicaragua (n=24) with and without colloidal silver coatings were analyzed in a laboratory setting. Both reagent grade laboratory water and stream water were used as influent matrixes. Microbial removal was assessed by spiking 6L of water per filter with 106/ml of E. coli and MS2 bacteriophage. The influent and effluent were analyzed for spiked microbes and removal efficiencies were determined. With reagent grade water, colloidal silver lined filters from Honduras and Nicaragua demonstrated bacterial removal averaging 4.35 and 3.43 logs, respectively, and viral removal averaging 0.60 and 0.42 logs, respectively. Using spiked stream water, bacterial removal averaged to 4.64 and 4.06 logs, respectively, and viral removal averaged to 1.29 and 0.56 logs, respectively. Non-silver filters had minimal microbial reduction. In conclusion, silver coated CWFs were able to remove substantial levels of bacteria, but were limited in their capacity to remove viruses. However, 1 of 15 Honduran and 15 of 24 Nicaraguan filters had inconsistent microbial removal in reagent waters potentially due to reduced manufacturing quality control, necessitating further investigation of production variability.     
 
Poster Number    11      
Applicant Name    David Hanna      
Project Title    Disparities in HIV-related mortality in persons with HIV infection by state, 34 US states, 2001-2006      
Descriptive Abstract Summary    Introduction:  Geographic disparities in HIV-related mortality highlight areas that may require more resources.  Published US HIV-related death rates by state have used general population denominators.  We used HIV-infected population denominators to control for prevalence differences among states, better reflecting the quality of care.

Methods:  We calculated HIV-related death rates per 1,000 HIV-infected person-years among persons age 15+ for 2001 through 2006 by state, age-adjusted to the 2000 US Standard Population.  Numerators were HIV-related deaths (defined by ICD-10 codes B20-B24) by state of residence at death from the National Vital Statistics System, which records the underlying cause of all US deaths.  Denominators were person-years based on yearly differences between cumulative HIV infection diagnoses and cumulative deaths among persons with those diagnoses, adjusted for reporting delays, by state of residence at diagnosis.  Denominator data came from the national HIV/AIDS Reporting System, which documents all persons diagnosed with HIV infection and their deaths, as reported to state health departments.  Negative binomial regression determined rate ratios (RRs) among states, adjusted for age, sex, race/ethnicity, and year.  Analysis was limited to 34 states with confidential name-based HIV reporting for at least four years.

Results:  Based on 2,437,274 HIV-infected person-years, the overall death rate due to HIV was 22.8/1,000 person-years (95% confidence interval [CI], 22.5-23.2).  Rates by state ranged from 10.5 (95% CI 8.8-12.3) to 35.2 (95% CI 31.8-38.7), showing significant heterogeneity across states even after adjusting for race/ethnicity (p<0.0001).  Rates increased by age (RR 1.36 per decade, 95% CI 1.35-1.38) and decreased by calendar year (RR 0.91, 95% CI 0.90-0.91).  States with the 11 highest rates were all in the southern region. 

Conclusions:  Our findings suggest that, among US states, the need for more resources to prevent HIV-related mortality is concentrated disproportionately in the South.  Policymakers should consider state or regional differences within a country when analyzing death rates.      
 
Poster Number    12      
Applicant Name    Ilene Browner      
Project Title    Effect of Cognitive Impairment on Colorectal Cancer Screening Among African American Older Adults      
Descriptive Abstract Summary    Purpose: To describe the prevalence of cognitive impairment (CI) and its association with adherence to colorectal cancer (CRC) screening among African American (AA) older adults in Baltimore, MD.

Methods: We examined baseline data from a screening trial within the Cancer Prevention & Treatment Demonstration (CPTD) project, designed to address disparities in cancer prevention & treatment among racial & ethnic minorities. Potentially eligible subjects - age ?65 yrs, Medicare enrollment parts A & B; AA; residence in Baltimore; no history of active cancer - were identified through the rosters of the Centers for Medicare & Medicaid Services & venue-based sampling. Participants responded to a standardized questionnaire administered face-to-face by a trained interviewer which included demographics & medical and cancer screening histories. CI was assessed by the Mini-Cog, a simple screening tool, which has been validated in multiple ethnic groups. We conducted univariate & multivariate analyses to determine the association between CI & having been screened by colonoscopy within the previous 10 yrs. Covariates were demographics, comorbidity, knowledge of Medicare coverage for cancer screening, & having Medigap insurance.

Results: Participants (n=826) had a median age of 71 years (range 65-85 yrs) with 10% >79 yrs, & 75% were women, 70% had ? 12 yrs education, & 40% reported an annual income > $20,000. Forty-two percent participants had CI, in univariate analysis, they were less likely to be adherent to CRC screening compared to those with CI (72.1% vs. 82.1%, p=0.0006). Other factors related to poor adherence were lower income, less education, being single, lack of Medigap, more ER visits, & ? 2 comorbid conditions. In multivariate analysis, adjusting for age, gender, education, income, marital status, knowledge of Medicare coverage for cancer screening, comorbidity & Medigap, CI was associated with a 35% decreased odds of being adherent with CRC screening (OR=0.65; 95%CI 0.44,0.96).

Conclusions: In this cohort of AA older adults, CI may be more common than previously perceived; and there is a statistically significant association between CI & poor adherence to CRC screening. These observations have profound implication for CRC control.     
 
Poster Number    13      
Applicant Name    Sarah Lynne      
Project Title    An Investigation of the Underlying Latent Structure of Deviance in Adolescence      
Descriptive Abstract Summary    Many different theories have been developed to describe deviant behavior during adolescence.  A general theory of crime conceptualizes all deviant behaviors (e.g., aggression, substance use, etc.) as arising from a common underlying disposition towards general deviance (Gottfredson & Hirschi, 1990).  This assumes that the underlying latent structure of deviance is one continuously distributed construct.  Other theories of deviant behavior, such as problem behavior theory (Jessor, 1992), posit that different deviant behaviors cluster together but this is not necessarily due to a single underlying latent structure of deviance.  Rather, qualitatively different classes of deviance manifest as deviant behavior clusters.  Currently available latent variable models allow for the estimation of latent constructs of deviance.  These statistical techniques usually presuppose the type of underlying latent structure of deviance, continuous or categorical, which may or may not reflect the true ontological status of deviance.  Masyn and colleagues (2008) developed a comparative statistical technique based on what they term the Dimensional-Categorical Spectrum, which allows researchers to investigate empirically the underlying latent structure most consistent with the observed data through the systematic examination of a candidate set of general factor mixture models (e.g., factor analysis, semi-parametric factor analysis, discretized latent trait analysis, factor mixture analysis, latent class analysis, etc.).  The fits of all the candidate models (estimated with maximum likelihood) are compared using a set of information-heuristic indices and the optimal model is selected.

First, this study will explore the underlying latent structure of deviance in a sample of urban, minority adolescents.  Second, this study will evaluate a.) if the underlying latent structure of deviance is similar in early versus late adolescence, and b.) if it is similar for males and females. The participants for this study (n = 225) come from the control group of a randomized controlled trial and were followed longitudinally from 1st grade through age 18 (53.2% male, 86.8% Black, 13.2% White).  Analyses will evaluate the underlying latent structure of multiple deviant behaviors (e.g. substance use, aggression, gambling) in 8th and 11th grades.

Determining the most probable latent structure of deviance based on observed data has important implications for theoretical conceptualizations of deviance as well as prevention of deviant behavior in youth and adolescents.  Information on the stability of the underlying latent structure of deviance across adolescence and between males and females has the potential to facilitate gender and age appropriate effective preventive interventions or validate current universal intervention strategies.     
 
Poster Number    14      
Applicant Name    Dilini Ranatunga      
Project Title    Effects of cell-type specific hIL-10 expression on disease susceptibility      
Descriptive Abstract Summary    IL-10 is an immunoregulatory cytokine produced by many cell types. Studies in mice suggest the cellular source of IL-10 plays a critical role in determining disease outcome. Yet the effects of tissue specific human IL-10 (hIL-10) expression are not well understood. To address this issue, we generated a hIL-10 transgenic mouse using a bacterial artificial chromosome (hIL10BAC). The hIL10BAC contains most if not all the regulatory sequences that govern hIL-10 production thus allowing tissue specific expression.  As hIL-10 is biologically active in the mouse, reconstituting Il10-/- mice with the hIL10BAC allowed us to evaluate the effects of hIL-10 on known IL-10 dependant phenotypes. Expression of IL-10 from myeloid sources in WT mice protects against lethal endotoxic shock. Faithful expression of the hIL10BAC in myeloid cells rescued Il10-/- mice from this fate. In contrast, T-cell-derived IL-10 leads to high parasite burdens in the livers and spleens of WT mice infected with Leishmania Donovani. However both Il10-/- and Il10-/-/hIL10BAC mice cleared the parasites. The failure to reproduce the susceptibility phenotype is attributed to weak hIL-10 expression in CD4+ T cells. Similarly, inflammatory bowel disease (IBD) is also IL-10-dependant and resistance is thought to involve T-cell-derived IL-10. Surprisingly, we found that the hIL10BAC rescues Il10-/- mice from IBD, suggesting differential regulation of hIL-10 in CD4+ T cells found in the gut versus the spleen.     
 
Poster Number    15      
Applicant Name    Tianjing Li      
Project Title    Setting Priorities for Comparative Effectiveness Research: A Case Study Using Primary Open-Angle Glaucoma      
Descriptive Abstract Summary    Objective: To test the feasibility of a framework for prioritizing new comparative effectiveness research questions related to management of primary open-angle glaucoma (POAG) using practice guidelines and a survey of clinicians.

Design: Cross-sectional survey

Participants: Members of the American Glaucoma Society

Methods: We restated as an answerable clinical question each recommendation in the 2005 American Academy of Ophthalmology Preferred Practice Patterns (PPPs) regarding the management of POAG. We asked members of the American Glaucoma Society to rank the importance of each clinical question, on a scale of 0 (not important at all) to 10 (very important), using a two-round Delphi survey conducted online between April and September 2008. Respondents had the option of selecting “no judgment” or “research has already answered this question” to each question in lieu of the 0 to 10 rating. We used the ratings assigned by the Delphi respondents to determine the importance of each clinical question.

Main Outcome Measure: Ranking of importance of each clinical question
Results: We derived 45 clinical questions from the PPPs. Of the 620 American Glaucoma Society members invited to participate in the survey, 169 completed the Round One survey; 105 of 169 also completed Round Two. To address the challenge in analyzing the response “research has already answered the question”, we assumed first that this represented a missing response, and subsequently that this response corresponded to the highest ranking. Nine clinical questions ranked as the most important under both of these assumptions:  four on medical intervention, four on filtering surgery, and one on adjustment of therapy.

Conclusions: Our theoretical model for priority setting for comparative effectiveness research question is a feasible and pragmatic approach that merits testing in other medical settings.     
 
Poster Number    16      
Applicant Name    Dionne Robinson      
Project Title    Inflammatory Responses to H1N1 Influenza Virus in Female Mice is Modulated By Estrogen      
Descriptive Abstract Summary    Data from the 1918 H1N1 influenza pandemic, the H5N1 avian influenza outbreak, and the current 2009 H1N1 pandemic, reveal that sex is one fundamental determinant of morbidity and mortality associated with influenza A virus infection of young (18-40 years of age) adults. Males and females differ biologically, though the implications of these differences on influenza pathogenesis are not well characterized. Generally, females mount more robust immune responses to viral challenge than males, correlating with efficient clearance and greater antibody production at the cost of developing immunopathology. To test the hypothesis that males and females respond differently to influenza A viruses and that sex steroid hormones may be involved, we inoculated adult (6-8 weeks) male and female C57BL/6 mice with the mouse-adapted influenza A virus, A/Puerto Rico/8/34 (PR8; H1N1) and monitored them daily for 21 days or euthanized them at select time points during the first week post-inoculation (p.i.). Infection of adult mice with PR8 significantly affected reproductive function by dysregulating the estrus cycle (i.e., increasing the number of days in diestrus) and concentrations of 17?-estradiol (E2) and progesterone (P4) in females and reducing concentrations of testosterone (T) in males. Female mice also lost significantly more weight, showed a greater reduction in body temperature, and were more likely to die following inoculation with influenza than males. Although virus replication kinetics in the lungs were similar between the sexes during the first week p.i., females had significantly higher concentrations of IFN-?, MIP-1?, MCP-1, and TNF-? in the lungs than males. To assess the role of sex steroid hormones in modulating the immune response to influenza, adult male and female mice remained intact or were bilaterally gonadectomized. Among gonadectomized mice, half received exogenous time-release capsules filled with T (for males) or E2 (for females) to maintain concentrations at a high steady-state for the duration of infection.
Manipulation of T concentrations in males did not significantly impact virus titers in the lungs, concentrations of cytokines and chemokines in the lungs, morbidity, or mortality. In contrast, gonadectomized females that received exogenous E2 had significantly lower concentrations of IFN-?, MCP-1, and TNF-? in the lungs and increased rates of survival as compared with gonadectomized and gonadally-intact females. Manipulation of E2 in females had no effect on virus replication in the lungs. In summary, influenza dysregulates hormones and immune responses in females resulting in greater immunopathology and death as compared with males. Sex steroids, in particular E2, regulate responses to infection by suppressing inflammatory responses and increasing survival in females. Studies are currently on going to elucidate the mechanisms by which E2 modulates immune responses to influenza A viruses. This research is supported by NIH grant AI079342.     
 
Poster Number    17      
Applicant Name    Christen Fornadel      
Project Title    Analysis of Anopheles arabiensis blood feeding behavior in southern Zambia during the two years following the introduction of insecticide treated bed nets.      
Descriptive Abstract Summary    Anopheles arabiensis is the primary vector responsible for Plasmodium falciparum transmission in Macha, Zambia. Since insecticide treated bed nets (ITNs) have the potential to alter host feeding behavior, the extent of the vector’s zoophilic and exophagic tendencies was evaluated during the two rainy seasons following ITN introduction. Paired indoor/outdoor human landing catches (HLCs) and outdoor cattle-baited collections were used to assess potential changes in host preference. Results support the hypothesis that An. arabiensis in Macha remains highly anthropophilic despite high ITN use. Additionally, HLCs and Centers for Disease Control light traps were employed to determine if ITNs were having an effect on foraging behavior. Similar numbers of mosquitoes were caught in light traps hung next to treated and untreated bed nets, suggesting that ITNs have little effect on entering behavior. Although no repellant effect was observed, An. arabiensis in Macha appears to be relatively exophagic and has been caught biting outdoors both right after sunset and right before sunrise, potentially circumventing the protective effects of ITNs.     
 
Poster Number    18      
Applicant Name    Jesse Berman      
Project Title    Health Benefits from Large Scale Ozone Reduction in the United States      
Descriptive Abstract Summary    Tropospheric ozone is one of six “criteria” air pollutants for which the U.S. Environmental Protection Agency (EPA) sets a health-based National Ambient Air Quality Standard (NAAQS).  The EPA monitors levels of ozone across the United States (US) through a network of air quality monitors.  Increased levels of ozone have been correlated with increased risk of adverse health effects, including premature mortality and related cardiopulmonary and respiratory morbidity.  In 2008, the United States Environmental Protection Agency (EPA) lowered the ozone NAAQS from 84 ppb to 75ppb, expressed as the maximum 8-hr average over a 24-hr period.  Based on current monitoring data, ozone levels in numerous locations across the U.S. exceed this standard.  The avoided potential adverse health impacts are quantified among the U.S. population associated with attaining the current and two alternative ozone NAAQS levels.  We estimate the avoided health impacts occurring after “rolling back” ozone values to just attain three alternate 8-hr ozone NAAQS: 75, 70, and 60 ppb (a range under current consideration for a revised ozone standard).  The two lower alternatives reflect the upper and lower-bound range of EPA Clean Air Scientific Advisory Committee recommended values.  The EPA Environmental Benefits Mapping and Analysis Program (BenMAP) is used to project the number of avoided cases of premature mortality and morbidity for an analysis year of 2007.  Using a suite of short-term ozone mortality studies (Bell et al. 2005 and Levy et al. 2005) the avoided incidences from current ozone-related all-cause premature mortality range from 290-410 at 75ppb, 580-820 at 70ppb, and 1,890-2,660 at 60ppb.  We also find that attaining the 75ppb standard result in prevention of 290 emergency room visits (respiratory) and 250 hospital admissions (respiratory), with a reduction of 550,250 acute respiratory symptoms and 237,100 lost school days.  Attainment of the 70 and 60 ppb 8-hr maximum levels yielded substantial additional health benefits, with about 1.1 and 3.5 million acute respiratory symptoms and 510 and 1,670 hospital admissions (respiratory) prevented at the 70 and 60ppb rollbacks, respectively.  Mapping of all scenario results display regional variation in health benefits, and reporting by metropolitan statistical areas (MSAs) show the greatest health benefits to be in the New York, Los Angeles, Philadelphia, and Riverside, California MSAs.       
 
Poster Number    19      
Applicant Name    Miho Tanaka      
Project Title    Influence of Interpersonal Communication on Perceived Risk of Lung Cancer      
Descriptive Abstract Summary    Research shows that interpersonal communication is an effective way to change personal beliefs about health risks, while mass-media is effective in raising awareness or knowledge about health issues.  A previous study on skin cancer concluded that those who discussed skin cancer with others were more likely to have higher perceived risk of skin cancer.  This study examined whether the interpersonal communication with friends or family members would increase perceived risk of developing lung cancer, with 1,872 survey participants who responded to the mental model section for lung cancer of the Health Information National Trend Survey (HINTS) 2005.  The effects of the interpersonal discussions with close associates were assessed, controlling for a variety of socio-demographic variables.  An independent variable of primary interest was the frequency of discussing health information with close associates.  Bivariate analyses indicated that age group, race/ethnicity, annual household income, marital status, educational attainment, the number of community organizations a survey respondent belonged to and frequency of discussing health issues with close associates were associated with the perceived risk of developing lung cancer (P<0.01).  Older, more educated, higher income and married respondents were less likely to believe they were at risk of developing lung cancer. Multivariable logistic regression analysis indicated that those who had frequent discussions of health issues with close associates were more likely to perceive themselves at risk compared to those who had never discussed health issues with others.  However, this relationship was not significant after controlling for socio-demographic variables and smoking history.  Of all the covariates, age group, household income and smoking history were the strongest predictors (p<0.001) of the perceived risk.  Interpersonal communication is a potential means to increase perceived risk and to encourage individuals to adopt protective behavior, however, it may not be effective for high-income or older individuals.     
 
Poster Number    20      
Applicant Name    Talibah Metcalf      
Project Title    Characteristics of trafficking and long-term maintenance of B-cells in the central nervous system in response to Sindbis virus infection      
Descriptive Abstract Summary    Alphaviruses are mosquito-borne message-sense RNA viruses that can cause encephalitis in a wide range of vertebrates including humans. Previous studies with Sindbis virus (SINV), the prototype alphavirus, have shown that infectious virus is cleared within 7-9 days, but that viral RNA persists. IFN-gamma plays a role in noncytolytic clearance of virus from neurons and anti-viral antibodies are important for both viral clearance and suppression of viral reactivation. After recovery, SINV-specific antibody secreting cells are present in the central nervous system (CNS) for the life of the animal. However, little is known about the changing functional characteristics of B-cells and important determinants of B-cell trafficking and long-term maintenance in the CNS.  To characterize the B-cell subset populations in the periphery and CNS tissue, as well as to understand the role of chemokines, C57BL/6 mice were infected intracerebrally with SINV and tissue was assessed at various times after infection by flow cytometry and qRT-PCR.
 
Plasmablasts and memory B-cells (CD19+CD38+CD138-IgM-IgD-) were 70% of the B-cell population for at least 6 months, while plasma cells (CD19+/-CD38-CD138+) were less than 5% of the population. Staining for intracellular and surface IgG at day 60 identified 40% of the B cells as plasmablasts and 50% as memory cells.  A small population of CD19+CD38-CD138- cells, characteristic of germinal center B-cells, was detected and this was confirmed by staining for the germinal center marker GL7. Levels of CXCL9/CXCL10/CCL3/CCL5 (leukocyte trafficking), CCL19/CXCL13 (follicle formation), and BAFF (B-cell survival) mRNAs peaked between days 5-7 after infection, followed by a gradual decreased and return close to baseline by 6 months, except for BAFF that was maintained at a low level. The expression of CXCR3 (receptor for CXCL9/10), CCR5 (receptor for CCL3/5), CCR7 (receptor for CCL19), and BAFF receptor was detected on CNS B-cells. 

These results show that plasmablasts and memory B-cells are present for months after infectious virus has been cleared and could play a role in the long-term suppression of SINV replication.  The detection of germinal center B-cells along with the early upregulation of chemokines involved in follicle formation suggest the formation of germinal centers in the brain in response to SINV infection.  The low levels of BAFF mRNA coincide with the low number of B-cells present after 2 months suggesting the brain provides a microenvironment for differentiation and survival of these cells.      
 
Poster Number    21      
Applicant Name    Sapeckshita Agrawal      
Project Title    Characterization of a novel periplasmic carbohydrate fibril in Myxococcus xanthus      
Descriptive Abstract Summary    Periplasmic glucans are a feature shared by many Gram-negative bacteria. These glucans exist either as linear (E. coli) or cyclic (Rhizobium spec.) polymers with an average length of 6-8 glucose residues. The main function of periplasmic glucans is the osmotic regulation of the periplasmic space, which is achieved through anionic groups attached to the polymers. Here we describe a novel, high molecular weight, periplasmic polysaccharide polymer in the soil bacterium Myxococcus xanthus that forms large fibril-like structures that resemble more extracellular polysaccharides than periplasmic glucans. HPLC analysis shows that this polymer is composed of Glucosamine, Galactosamine, Mannose and Glucose and is formed by hundreds or even thousands of sugar residues. We are currently characterizing the structure, composition, size, and function of this polymer in Myxococcus xanthus and potential homologue polymers in other bacteria including important human pathogens.      
 
Poster Number    22      
Applicant Name    Mara McAdams      
Project Title    The association of obesity on prevalent hyperuricemia and incident gout in women in the Atherosclerosis Risk in Communities (ARIC) Study      
Descriptive Abstract Summary    Purpose: Previous research in gout has focused on men. The effect of anthropometric risk factors on prevalent hyperuricemia and incident gout in women is unclear. In the Atherosclerosis Risk in Communities (ARIC) Study, we evaluated the association of obesity with hyperuricemia and gout in women. 

Methods: ARIC is a population-based cohort of 15,792 individuals (8,710 women) aged 45-64 at enrollment who participated in four examinations (3 years apart). We restricted our study population to Caucasian and African-American women with no history of gout at their first study visit. Serum urate was measured at visits 1 and 2, and we used the mean of these two measures.  Hyperuricemia was defined as a mean serum urate greater than 7.0 mg/dL. Anthropometric variables were obtained at baseline and included body mass index (BMI) and waist-to-hip ratio (WHR). BMI was examined as continuous and categorical (<25, 25-30, 30-35, >35 kg/m2) variables. Obesity was defined as BMI greater than 30. High WHR was defined as > 0.8. Weight change was calculated by subtracting the participant’s weight at cohort entry from her self-reported weight at age 25. Weight change was categorized as: no weight change (weight loss or gain <10 lbs), low weight gain (weight gain of >10 to <30lbs), and high weight gain (>30 lbs). The multivariable model was adjusted for baseline age, race, diuretic and oral contraceptive pill use, menopausal status, hypertension, diabetes, and chronic renal insufficiency. Incident cases of gout were identified by self-report at visit 4.

Results: Of the 8,505 women with serum urate measurements, 14.9% were hyperuricemic. Obesity, WHR, and weight change were significantly associated with baseline hyperuricemia. The association remained after adjusting for known risk factors for hyperuricemia. Additionally, 113 women  (1.3%) developed gout over nine years of follow-up.  At baseline, all of the women who developed gout were obese, yet only 38% were hyperuricemic.

 
    Unadjusted risk of hyperuricemia    Adjusted risk of hyperuricemia      
    PR    CI    PR    CI      
BMI (5 kg/m2) change    1.53    1.49, 1.57    1.40    1.35, 1.45      
BMI                      
<25  (reference)    1.0        1.0          
25-30    2.68    2.24, 3.21    2.21    1.84, 2.64      
30-35    4.90    4.11, 5.85    3.55    2.95, 4.26      
35-40    7.33    6.18, 8.70    4.88    4.04, 5.90      
Obese    3.33    3.01, 3.69    2.44    2.18, 2.73      
High WHR    4.35    3.24, 5.84    3.04    2.26, 4.09      
Weight change                      
No change (reference)    1.0        1.0          
Low weight gain    1.43    1.14, 1.81    1.41    1.12, 1.77      
High weight gain    4.03    3.29, 4.94    3.09    2.52, 3.79     

Conclusions: In a population-based cohort of middle-aged women, we found obesity, high WHR and weight gain to be strongly associated with hyperuricemia. Additionally, all women who developed gout over nine years of follow-up were obese at baseline. Obesity is a risk factor for hyperuricemia and may be useful for prediction of incident gout in women.      
 
Poster Number    23      
Applicant Name    Rosemay Remigio-Baker      
Project Title    A Bi-Directional Association Between Elevated Depressive Symptoms And Overweight Or Obesity In Women: The Multi-Ethnic Study Of Atherosclerosis (MESA)      
Descriptive Abstract Summary    Background: Cross-sectional studies show an association between depression and overweight/obesity; however, the temporality of the association is unclear.

Methods: We examined the direction of association between overweight/obesity and elevated depressive symptoms in the Multi-Ethnic Study of Atherosclerosis (MESA).  The study population consisted of 5,031 non-diabetic men and women aged 45-84 years at baseline in 2000-2002 and followed until 2005-2007.  Participants were categorized as either normal (body mass index [BMI] < 25kg/m2) or overweight/obese (BMI > 25kg/m2).  Depressive symptoms were defined as a Center for Epidemiologic Studies Depression Scale Score (CES-D) ? 16 or anti-depressant medication use.  To evaluate the direction of association between depressive symptoms and overweight/obesity, two longitudinal analyses were conducted using Cox Proportional Hazards Models.  In 1,496 normal weight participants at baseline, we estimated the relative hazard (RH) of incident overweight/obesity by baseline status of depressive symptoms.  In 3,801 participants without baseline depressive symptoms, we calculated the RH of developing the condition by baseline weight status.      

Results: Among women with baseline depressive symptoms, the RH for developing overweight/obesity over 4 years was 1.54 (95% CI:  1.08 to 2.22), following adjustment for age, race, MESA site, income, education, inflammatory markers, and health behaviors (current smoking status, daily caloric intake, exercise).  By contrast, in men, the association between depressive symptoms at baseline and incident overweight/obesity was not elevated (RH=0.89; 95% CI:  0.55 to 1.47).  Overweight/obesity at baseline was associated with incident depressive symptoms in women (RH=1.27; 95% CI:  1.00 to 1.61, p=0.049) but not in men (RH=0.83; 95% CI:  0.60 to 1.13).  Interaction was marginal by sex (p=0.05), but not significant in either analyses by race.   

Conclusion: A bi-directional, longitudinal association between overweight/obesity and depressive symptoms was found in women, but not in men.  This association was not explained by socioeconomic factors, inflammation or health behaviors.       
 
Poster Number    24      
Applicant Name    Andrea Radtke      
Project Title    Migration of P. berghei sporozoites to the draining lymph node is required for CD8+ T cell priming      
Descriptive Abstract Summary    Immunization with irradiated sporozoites elicits protective CD8+ T cell responses against malaria. Priming and differentiation of CD8+ T cells depends on the first interactions between naïve T cells and professional antigen presenting cells (APCs).  Therefore, a major focus of vaccine research is the identification of the antigen presenting events critical for CD8+ T cell priming.  Using a murine model of malaria infection, we have demonstrated that antigen specific CD8+ T cells are primed by dendritic cells in the lymph nodes draining the site of inoculation.  To determine whether sporozoite migration to the draining lymph node is required for CD8+ T cell priming, we created a transgenic Plasmodium berghei parasite that is unable to exit the dermis and reach the draining lymph nodes or the liver site of infection (P. berghei CS5MDN). Intradermal inoculation of P. berghei CS5MDN sporozoites failed to induce robust antigen specific CD8.+ T cell responses in wild type C57/B6 mice as compared to control sporozoites.  These studies demonstrate that sporozoite migration to the draining lymph node is likely critical for CD8+ T cell priming following sporozoite immunization.     
 
Poster Number    25      
Applicant Name    Ronald Stamper      
Project Title    Ras Regulation of GPI Anchor Biosynthesis in Yeast      
Descriptive Abstract Summary    One method by which proteins are anchored to lipid membranes in eukaryotes is by attachment of a glycosylphosphatidylinositol (GPI) anchor.  This anchor is preassembled in the endoplasmic reticulum and subsequently attached near the C-terminus of a target protein by a highly conserved enzymatic pathway.  The anchored protein then traverses the secretory system to reach the plasma membrane, where the protein is displayed in the extracellular compartment.  These proteins may remain attached to the membrane or may be cleaved from their anchors for release to the environment.  In yeast, GPI anchored proteins are frequently cleaved from their anchors for attachment to the cell wall, and in this way they comprise a major structural component of the yeast wall. 

Previous work in our lab has shown that the process of GPI anchoring in the model yeast Saccharomyces cerevisiae is regulated by the binding of the small G-protein Ras2 to the first enzyme complex of the pathway, the GPI-GlcNAc Transferase.  This complex, consisting of at least six proteins in yeast and mammals, represents only the second known target of Ras2 regulation in yeast.  Yeast Ras2 is homologous to the mammalian Ras oncogenes, which show upregulated activity in some 30% of human cancers.  Additionally, the human proteome includes homologs to each of the components of the yeast GPI-GlcNAc transferase complex.  This allows speculation about this potential new signaling pathway for mammalian Ras proteins through the GPI anchor biosynthetic pathway, especially as related to Ras-related cancers.

The current work aims to elucidate the mechanism of regulation of the yeast GPI-GlcNAc complex by Ras2.  The protein subunit within the complex which directly binds to Ras2 has been identified.  That interaction has been disrupted by site-directed mutation of the binding site in the target protein.  Finally, the phenotypic consequences of this regulation are being assessed in order to gain insight into this novel form of Ras regulation in yeast.  In addition to the basic biological insights, we hope to gain information which can be further investigated in human cancers.       
 
Poster Number    26      
Applicant Name    Gwenyth Lee      
Project Title    Effect of Malaria Vivax Infection on Growth among Children in the Peruvian Amazon      
Descriptive Abstract Summary    Background: Few prospective studies have examined the impact of malaria on child growth directly, and none to our knowledge have examined the effect by type of parasite.  Our goal was to quantify the effect of plasmodium vivax infection on ponderal and linear growth velocity in children, in an endemic area in the Peruvian Amazon region. In this region, the majority of individuals with parasitemia are symptomatic.

Methods:  A 43-month-long prospective, community-based cohort was established to explore the epidemiology of diarrhea among 438 children 0-72 months of age in the Peruvian Amazon. Participants reported all medications taken over the study period, including medications prescribed uniquely for vivax malaria and distributed by only one local health post.  Probable episodes of vivax malaria were reconstructed from this data. 
Longitudinal models that included child-level mixed effects and controlled for age,  socioeconomic status, seasonality, diarrheal disease, and non-diarrheal, non-malarial fever were fitted to test the effect of vivax incidence on 2-month, 4-month, and 6-month weight and height velocity.

Results: 228 vivax infections were identified over 11,768 child-months. 313 children were never infected, 63 children experienced one infection, and 62 experienced more than one. Infection was most frequent in May and least frequent in October.  Participants with vivax malaria infection tended to come from families in which the mother had significantly less formal education, in which the family was less likely to own a latrine, and in which the per capita income was lower. However, they were similar to uninfected children in birth weight, birth height, and mean anthropometric status (WAZ and HAZ) over the course of the study period. Malaria infection led to deficits in weight gain of 108 grams and 55 grams over 2 and 4 months respectively, and a deficit of .07 cm in height gain over 2 months. However, vivax episodes did not have a significant impact on weight gain at 6 months or on height gain over 4 or 6 months. 

Conclusions: Vivax malaria in children led to poor short-term weight gain, which persisted over intervals as long as 4 months.  However, unlike diarrhea, it was not associated with long term weight and height velocity deficits.  This may be related to the fact that, in this environment, vivax infection is infrequent, while diarrhea infection is highly common, leading to greater possibility for catch-up growth following infection.      
 
Poster Number    27      
Applicant Name    Rama Salhi      
Project Title    Neighborhood drug markets and sex partner concurrency among young African American women      
Descriptive Abstract Summary    Background: Sexually transmitted infections (STIs) including HIV disproportionately affect young African American women. Individual-level risk factors, although important, do not completely account for the disparities observed.  A growing body of evidence suggests that environmental-level factors may play a role. The existence and intensity of neighborhood drug markets, for example, may alter the structure of sexual networks within a neighborhood. Specifically, we hypothesize that neighborhood drug markets, through changes in norms around sex partner preferences and/or in the types of sex partners available for partnering, increase the likelihood for a young African American woman to select a sex partner who practices concurrency. Concurrency is one measure of network structure and is defined as overlapping sexual partnerships in time.  Concurrency has been shown to be associated with increased risk for bacterial STIs. 

Objectives: To determine whether resident perceptions of neighborhood drug markets are associated with increased risk for partnership with an individual who practices concurrency among a household sample of young, urban, African American females, adjusting for the neighborhood poverty level.

Methods: Data for this study came from two sources including a household study and the U.S. Census 2000. The household study target population included English-speaking, sexually active 15-24 year olds residing in Baltimore, MD. Among 486 eligible census block groups (CBGs), a sample of 65 was selected using a stratified, systematic, probability proportional to size sampling strategy. Within the 65, 13,873 households were selected for study inclusion. From April 2004 to April 2007, research assistants administered an audio-CASI.  To generate the main effect variable, participant reports of neighborhood drug markets on four items were summed and averaged to create individual scores (Cronbach’s alpha 0.82).  Individual scores were then summed and averaged to the neighborhood level (ICC=0.1206, p value < 0.001) to generate a neighborhood level measure of perceptions of drug markets (continuous scale). Participants were also asked to report on their sex partners in the past 90 days.  If a participant reported that any of the sex partners has other sex partners during the relationship with the participant, the participant was coded as having have a sex partner who practices concurrency (0,1).  Data on percent of households below the Federal poverty line was obtained from the U.S. Census 2000 to adjust for the poverty level of the neighborhood.

Logistic regression models using generalized estimating equations and sampling weights were used to test whether increased reports of neighborhood drug markets was associated with sex partner concurrency among African American females in two age groups, 15-18 years and 19-24 years after adjusting for the neighborhood poverty level. Post-hoc analysis of selected characteristics hypothesized to be related to sex partnering by age group were conducted to explore differences found in the main hypotheses by age group.

Results: A total of 599 sexually active youth residing in Baltimore were enrolled in the study and included in the generation of the measure of neighborhood drug markets.  A subsample of heterosexual, African American females (n=307) was then used for the remaining analyses. 
The regression models suggest that the odds of selecting a sex partner who practices concurrency significantly increased by almost 13 times (OR, 12.68; 95% CI, 1.50, 106.95) for every unit increase in neighborhood drug markets among African American females less than or equal to 18 years of age, after adjusting for the level of neighborhood poverty. Among African American females greater than 18 years of age, the odds of selecting a sex partner who practices concurrency was inversely, although not significantly, associated with average resident report in drug markets (OR, 0.33; 95% CI, 0.07, 1.45), after adjusting for the level of neighborhood poverty.  In a post-hoc analysis, African American females greater than 18 years old (vs. less than or equal to 18 years) were statistically significantly more likely to report at least one child (58.7% vs. 13.8%, p value < 0.001).

Conclusions: Increased reports of neighborhood drug markets were associated with having a sex partner who practices concurrency among African American women less than or equal to 18 years old.  Discrepancies seen in the association among individuals greater than 18 years old is likely due to differences in parity among these age groups which may in turn affect sex partner selection patterns. This study represents the first step in elucidating the mechanism through which drug markets may affect sexual networks and the position of individuals within these sexual networks.     
 
Poster Number    28      
Applicant Name    Ashish Jachak      
Project Title    Short Single Walled Carbon Nanotubes Are Extensively Trapped By Human Mucus       
Descriptive Abstract Summary    Engineered nanoparticles, such as short length single walled carbon nanotubes (sSWCNTs), are increasingly used for bone tissue engineering, chromatographic purifications and antioxidant functionality. Industrial-scale production of sSWCNTs likely leads to pulmonary exposure of workers in occupational settings. While most toxicology studies have focused on the toxicity of SWCNTs to cells, whether the SWCNTs can penetrate across the protective mucus coating in the lung airways remains unclear. Here we sought to investigate the transport of sSWCNTs of 2 different sizes (~ 60 nm and ~ 200 nm) in human mucus, which has specifically evolved to quickly trap and eliminate foreign particles. To improve their solubility, sSWCNTs are typically wrapped by single stranded DNA (ssDNA). We used high resolution multiple particle tracking to quantify the transport rates of hundreds of fluorescent sSWCNTs in fresh, undiluted human mucus. Time-lapse traces indicate that the diffusion of both sSWCNTs are strongly hindered in mucus. Using Fick’s 2nd law of diffusion, we estimated that virtually all sSWCNTs are unable to penetrate a 10 mm thick mucus layer even after 4 hrs. Since the deep lung has little mucus present, we further evaluated the uptake and clearance by macrophages (MH-S) and human bronchial epithelial cells (BEAS-2B). Within 30 min, sSWCNTs were internalized by MH-S cells, highlighting the importance of another protective mechanism of the respiratory tract. There was also substantial uptake of sSWCNTs by human bronchial epithelial BEAS-2B cells. Nevertheless, the viability of BEAS-2B cells was not affected even at very high concentrations (50 mg/ml). These data challenge the notion that sSWNCTs will inherently penetrate the mucus mesh and impose oxidative and inflammatory stress on the underlying airway epithelia. Our work shows that sSWCNTs are extensively trapped by mucus and thus likely to be eliminated by mucociliary clearance, thus limiting their toxic exposure to airway epithelia.     
 
Poster Number    29      
Applicant Name    Melissa Opryszko      
Project Title    Factors affecting drinking water choices in rural Ghana after the introduction of Small Water Enterprises      
Descriptive Abstract Summary    The Johns Hopkins University Center for Water and Health is evaluating Small Water Enterprises (SWEs) in five Ghanaian villages. SWEs are found throughout the world vending water to households (HH) in regions beyond the reach of piped water systems.  Their ubiquity in the developing world suggests that they may prove valuable in improving potable water availability and access to vulnerable populations.    The community-based SWEs currently under study utilize advanced water kiosks that house sand filtration, activated carbon and ultraviolet light to treat surface water. Each village-level SWE aims to provide access to drinking water that meets World Health Organization (WHO) microbial guidelines at competitive market prices to HHs living below the poverty line.

In each of five villages the study consisted of a randomized selection of 100 GIS-coded HHs, key informant interviews and microbial and chemical testing of kiosk water as well as alternative drinking water sources.  HH surveys (n = 501) of female caretakers within study villages found that water vended by the SWE, meeting WHO microbial guidelines and sold at a relatively low-cost (approximately USD 0.05 per 18 liter container) was often bypassed for water that was of lower quality and/or more expensive.  Household drinking water choices were found to be made based on multiple factors including taste, distance between household and water source as determined by GPS tracking, perceived water quality, cost, belief systems and ancestral behaviors.  In many instances, treated kiosk water was purchased for household washing rather than for drinking.  These findings reinforce the need for community mobilization and behavior change communication programs to be embedded within SWE drinking water interventions to impact water collection behaviors.  Populations must be aware of the importance of drinking microbiologically safe water to prevent disease and reduce childhood morbidity and mortality.      
 
Poster Number    30      
Applicant Name    Yeny Tinoco      
Project Title    Burden of illness and risk factors for transmission of seasonal influenza in four distinct regions of Peru.      
Descriptive Abstract Summary    Introduction: Since early April 2009, the world has been responding to a pandemic of a novel H1N1 influenza A virus (pH1N1). Epidemiological data on pH1N1 collected the Southern Hemisphere has helped with planning for the current influenza season in the Northern Hemisphere. In mid-June 2009, through a joint collaboration, the Naval Medical Research Center Detachment in Peru, the CDC and the Peruvian Ministry of Health implemented a prospective population-based cohort study to better define the epidemiology of seasonal influenza and other respiratory viruses in a developing country, specifically Peru. We report on data from the first months of this study, describing the epidemiology of ILI and pH1N1 in this population.
Methods: Households from four geographically disparate and ecologically distinct locations of Peru (Tumbes, Lima, Cusco and Madre de Dios) were randomly selected to participate in the study. All household members were eligible for enrollment and invited to participate. Subsequently, field workers performed screening visits to households three times per week to identify influenza-like illness (ILI) cases. The ILI case definition for individuals ?5 years of age included sudden onset of fever ? 38°C, with cough and/or sore throat. For children <5 years old, we considered rhinorrhea and/or nasal congestion in addition to fever ? 38°C with cough and/or sore throat. Once an ILI case was identified, both nasal and oropharyngeal swabs were collected, combined and placed into viral transport media, transported at 4°C to the laboratory and stored at -80C until processing. Laboratory diagnosis of pH1N1 was performed using the CDC 2009 pH1N1 real-time RT-PCR (rRT-PCR) assay. Attack rates (AR) and incidence rates (IR) were estimated by age group for ILI and pH1N1 confirmed cases, respectively.
Results: A total of 6548 individuals, living in 1432 households (approximately 350 per cohort site) were enrolled in the study from April until July, 2009. Screening visits were initiated on June, 25 and, as of January 23, 2010, 1343 ILI cases had been identified and 61.5% of them have PCR results for pH1N1. ILI cumulative attack rates have been higher in Tumbes (32.56 %), followed by Lima (26.79 %), Puerto Maldonado (14.10 %) and Cusco (9.01 %). Highest weekly ILI attack rates occurred earlier in Lima in epidemiological week (EW) 26, reaching 35.5 x 1000 person-weeks of follow up in comparison to Tumbes (28.4 x 1000 person-weeks of follow up) and Puerto Maldonado (14.34 x 1000 person-weeks of follow up ) that both presented picks of weekly ILI attack rates during EW 38. The numbers of ILI episodes per person during the study period were higher in Tumbes for all the age groups except for 10-17 and 50-59 years old when compared to the other sites. Of 96.3% individuals who provided a sample, the percentages of ILI due to infection with pH1N1, ranged from 24% - 48% in Cusco and Lima, respectively. The percentage of ILI due to pH1N1 was highest in the age group of 5-9 years (59.6%), followed by 56.9% in the 10-17 years old.
Conclusions: Most epidemiological information on influenza in Peru is based upon passive, inpatient and outpatient clinic surveillance data. These results provide the first unbiased description of the epidemiology of ILI and pH1N1 occurrence from a developing country as they are gathered from an active population-based surveillance system in 4 different ecological regions. We have identified differences in the epidemiology and transmission dynamics of ILIs and influenza across the 4 sites, perhaps due to their unique environmental and socioeconomic differences. As data is being generated by this population-based, study calculation of measures of disease impact for a larger population will be assessed. Such data may help inform pH1N1 mitigation strategies, surveillance strategies, and vaccination policy.     
 
Poster Number    31      
Applicant Name    Sudharsanam Manni Balasubramaniam       
Project Title    Temporal and seasonal trends in pneumonia associated childhood mortality (1998-2007) in Gadchiroli district, India      
Descriptive Abstract Summary    Background: Pneumonia accounts to about 20% of all deaths in children aged under five years. Studies show that community based approach by health workers using an algorithm and timely treatment with antibiotics reduce mortality due to pneumonia. However, little information is available on long term trends of pneumonia in populations where this approach is implemented for a longer period.

Objectives: To examine the temporal trends of pneumonia mortality and explore the trends in age and season specific pneumonia mortality from 1988 to 2007 in Gadchiroli, India.

Materials and Methods: This study was undertaken in Gadchiroli district of Maharashtra state in India. This non randomized community trial was started by Society for Education Action and Research in Community Health (SEARCH) in the year 1988. There were 58 villages in intervention areas (6176 children) and 44 villages in control areas (3947 children). The health workers were trained to use a standard algorithm of W.H.O to diagnose and treat pneumonia in children with antibiotic Co-trimoxazole. All children aged under five years in the intervention areas were treated for pneumonia by community health workers. The children in the control areas were treated by already existing system. Specific cause of mortality was assigned by verbal autopsy in both the areas using standardized questionnaires. This initial study was carried out till 1990 and was proven to be effective and results were published. This study is continued and monitored as a service program in the intervention areas by SEARCH till date. This project involved secondary analysis of the data of original study and the service program. The data from April 1988 to March 2008 was used for the current data analysis. Summary measures and indicators like incidence of mortality due to pneumonia, disease specific mortality due to pneumonia in different age groups were calculated for different years, seasons and age groups.

Results: There was a decline in mortality due to pneumonia in the children aged under five years in the intervention areas (from 8.7 per 1000 to 0.8 per thousand). During the first year after the trial the child mortality rate due to pneumonia was 8.79 per 1000 population of children aged under five years in the intervention areas and 14.44 per 1000 in the control areas and was higher than the intervention areas. This difference between the two areas continued till 2000. After 2000 the difference in child mortality was less obvious between intervention and control areas. On fitting a quadratic prediction line for the trends due to mortality in both areas, the mortality is progressively declining in both the groups. The decline in both areas slowed down after the year 2000.

On analyzing the trends comparing Infant and 1 to 5 years pneumonia specific mortality, the decline in mortality was progressive and steeper in less than one year of age when compared to the 1 to 5 years and this was seen throughout twenty years. The pneumonia mortality was more in the rainy season and then in winters and least in the summer. The mortality declined with time in all the seasons. The rate of reduction appeared to be more in the rainy season followed by winter and then summer. The difference in mortality between seasons became less obvious as time advanced.

Conclusions:
-    Community based approach of pneumonia management can effectively reduce childhood mortality due to pneumonia as revealed by the temporal trends.
-    The decline was sustained over the years and there was decline in mortality was in infants and toddlers, though the decline was pronounced in infants.
-    The pneumonia specific mortality decline was similar in all seasons and mortality has declined to a low level that the seasonal variations were no longer obvious.

Triggers for further research:
-    Examining for Individual determinants, operational issues, cost effectiveness of the approach and behavioral changes which helped in achieving and sustaining the effectiveness for twenty years can give several insights.
-    The attribution of trends in birth rate, female literacy rate, overall child mortality, socioeconomic status and changes in health seeking behavior for reduction of mortality can be studied as the control areas also showed decrease in mortality.
-    It is worthwhile to study the decline in both the intervention and control areas slowed down after sometime as it can throw light on factors that affect pneumonia specific mortality beyond a certain time in areas where community based approach is under implementation.     
 
Poster Number    32      
Applicant Name    Wen-Hsuan Lin      
Project Title    Route of Immunization Influences the Induction of Humoral, Cellular and Protective Immunity by Live Attenuated Measles Vaccine in Rhesus Macaques      
Descriptive Abstract Summary    Despite the availability of an effective live attenuated measles virus (MV) vaccine (LAV), measles remains a leading cause of vaccine-preventable morbidity and mortality worldwide. Maintaining high vaccine coverage is necessary for elimination of endemic measles transmission, but has been difficult in many developing countries. The respiratory route offers an opportunity to deliver vaccines through a needle-less platform, which may facilitate high vaccine coverage and avoid transmission of needle-borne diseases.  To date, the immune response induced by LAV given through respiratory route has not been systematically studied. In this study, measles seronegative, juvenile rhesus macaques were immunized with liquid Edmonston- Zagreb (EZ) measles vaccine targeting the upper airway through a nebulizer (LN, n=3), or by delivery through an endotracheal tube (LT, n=3) or parenterally by intramuscular injection (IM, n=3). A powder formulation of EZ LAV was also tested by administration through an endotracheal tube (PT, n=3). Both the route and depth of immunization significantly influenced the induction of the humoral immune response to LAV. Monkeys given the vaccine IM developed high titers of neutralizing antibody and long lasting MV-specific IgG while monkeys immunized by the respiratory route developed low titer and poor neutralizing antibody to MV. Among animals immunized through the respiratory route, liquid vaccine delivered via endotracheal tube (LT) induced better humoral responses with higher MV-specific IgG, higher hemagglutinin-specific IgG and better neutralization titers than liquid vaccine targeting upper airway (LN) or powder vaccine delivered via endotracheal tube (PT). Unexpectedly, the influence of route and depth of immunization on cellular immune response was not correlated with the humoral response. Animals in the LN group had the highest T cell responses to MV in comparison with the IM, PT and LT groups. On intratracheal challenge with wild type MV, the IM-immunized monkeys were fully protected while the respiratory tract -immunized monkeys showed signs of infection and viremia. Despite the fact that respiratory immunization did not prevent MV infection, animals primed with LN immunization showed an acceleration of viral clearance from both blood and respiratory tract compared to animals in the PT group that had no immunity to MV prior to challenge.  Moreover, the acceleration of MV clearance coincided with significantly faster and higher levels of MV-specific recall CD4+ and CD8+ T cell responses in animals in the LN group. Taken together, these studies demonstrate that the route of immunization influences the induction of humoral, cellular and protective immune responses to measles vaccine. Protection from measles correlates with neutralizing antibody and not with T cell responses. Furthermore, although memory T cells alone are not sufficient for preventing MV infection, a robust recall T cell response does accelerate viral clearance systemically and at the respiratory tract. To achieve the goal of eliciting protective immunity through respiratory delivery of LAV, it may be necessary to design vaccines and delivery devices that target the nasopharynx, as well as the lung.     
 
Poster Number    33      
Applicant Name    Shuzhen Sim      
Project Title    Dengue virus inhibits immune signaling in Aedes aegypti cells      
Descriptive Abstract Summary    The ability of many viruses to manipulate the host antiviral immune response often results in complex host-pathogen interactions. In order to study the interaction of dengue virus (DENV) with the Aedes aegypti immune response, we have characterized the DENV infection-responsive transcriptome of the immune-competent A. aegypti cell line Aag2. As in mosquitoes, DENV infection transcriptionally activated the cell line Toll pathway and a variety of cellular physiological systems. Most notably, however, DENV infection down-regulated the expression levels of numerous immune signaling molecules and antimicrobial peptides (AMPs). Functional assays showed that transcriptional induction of AMPs from the Toll and IMD pathways in response to bacterial challenge is impaired in DENV-infected cells. In addition, Escherichia coli, a Gram-negative bacterial species, grew better when co-cultured with DENV-infected cells than with uninfected cells, suggesting a decreased production of AMPs from the IMD pathway in virus-infected cells. Pre-stimulation of the cell line with Gram-positive bacteria prior to DENV infection had no effect on DENV titers, while pre-stimulation with Gram-negative bacteria resulted in an increase in DENV titers. These results indicate that DENV is capable of actively suppressing immune responses in the cells it infects, a phenomenon that may have important consequences for virus transmission and insect physiology.      
 
Poster Number    34      
Applicant Name    Sachiko  Ozawa      
Project Title    Trust Matters: Villagers’ Trust in Providers and Insurers & Their Demand for Community-Based Health Insurance in Cambodia      
Descriptive Abstract Summary    Objective: To understand the effect of villagers’ trust for health insurers and healthcare providers on enrollment in a community-based health insurance (CBHI) scheme in Cambodia.
Background: Community-based health insurance (CBHI) schemes have been launched in recent years to cover the costs of healthcare in order to reduce poverty associated with healthcare and improve access to health services. While these schemes have gained international support as part of a solution to healthcare financing problems, increasing subscription rates has faced challenges. The notion of prepayment for healthcare can be difficult to accept in developing countries, particularly where experience with such schemes is lacking and trust in relevant financing organizations is not well established.
Having a large enrollment base is important in CBHI schemes because it relies on the size of enrollment to pool financial resources and offer financial protection. Low enrollment rates can limit the coverage and protection these schemes can offer, and also make them vulnerable to bankruptcy. Increasing CBHI enrollment can ensure continued existence of these funds beyond donor support and enhance financial sustainability. It can also reduce the negative effects of adverse selection by attracting greater numbers of healthy individuals in the pool, which is necessary to maintain CBHI premiums at affordable rates to the community.
Methodology/Approach: The study was conducted in northwest Cambodia where a CBHI scheme operates with the highest enrollment rate (19%) in the country. Unlike other CBHI schemes in Cambodia with average enrollment rates of 1-4%, this scheme was started by members of the community and is run by a local Cambodian NGO. This study hypothesized that villagers’ relationships with health insurers and healthcare providers matter in their decisions to enroll in CBHI schemes. A mixed method approach was employed to gauge how individuals in the community trust the health insurer, public providers and private providers, and whether this plays a role in their decisions to enroll in CBHI schemes. Focus groups and a cluster random household survey were carried out to conceptualize the construct of trust and measure trust levels, and to explore the association of insurer trust, public and private provider trust, and enrollment in CBHI schemes using factor analysis and multinomial logistic regressions.
Findings: In the CBHI context, villagers’ trust appeared to consist of 5 main components: organizational trust, financial trust, personal interactions, honesty, & competence. Organizational trust displays villagers’ beliefs in the health facility or health insurance organization as an institution, while financial trust represents confidence in financial transactions with the health insurer or healthcare provider. Personal interactions demonstrate positive rapport with healthcare providers or employees of the health insurance organization. Honesty captures the perception that healthcare providers or the health insurer is telling the truth, while competence measures the perceived ability of healthcare providers and staff of health insurance organization to provide service at a level that meets their basic expectations. Trust scales for the health insurer, public provider and private provider were developed by drawing on these domains of trust. 
Statistically significant associations were found when assessing the relationship between insurer trust levels and CBHI enrollment. After controlling for demographic factors, healthcare utilization and household socio-economic status, standardized insurer trust levels for villagers who dropped-out (RRR=1.74, p<0.001), newly enrolled (RRR=1.80, p=0.001), and renewed insurance (RRR=3.08, p<0.001) were statistically significantly higher than those who never enrolled in CBHI schemes. For healthcare providers, villagers’ trust in public providers was found to be associated with CBHI enrollment. Standardized public provider trust scores for those who never enrolled in CBHI remained statistically significantly different from drop-outs (RRR=1.28, p=0.04), newly enrolled (RRR=1.45, p=0.02) and renewed individuals (RRR=2.56, p<0.001) after controlling for confounders. The study also confirmed the hypothesis of no association between trust for private providers and CBHI enrollment, since the CBHI scheme only provides coverage for public providers and not care offered by private providers.
Implications for policy: This study is the first to establish statistical associations between CBHI enrollment and healthcare provider trust, and between CBHI enrollment and CBHI insurer trust. It fills the gap in the existing literature of the association between trust and enrollment in CBHI schemes. The study confirms the hypothesis that villagers’ relationships with providers and insurers matter in their decisions to enroll in CBHI schemes, and provides an alternative explanation for villagers’ demand for CBHI. It also developed three trust scales which can be applied to measure insurer and healthcare provider trust in other CBHI contexts in low-income countries. The findings contribute to the knowledge-base on demand for voluntary health insurance and trust in health financing systems.
This study comes at an important point in time when the Cambodian government is developing policies and regulations to standardize CBHI schemes. The study draws attention to the need for public healthcare providers and health insurers to place greater emphasis on building trusting inter-personal relationships with villagers. The results illustrate the importance of considering villagers’ trust in the context of health financing systems in low-income countries, in order to improve health insurance enrollment, provide access to essential health services, and protect people in poor rural communities against the impact of health-related shocks.      
 
Poster Number    35      
Applicant Name    Jose Ramirez      
Project Title    The Toll pathway is a conserved immune defense active against different dengue serotypes and present in multiple Aedes aegypti strains      
Descriptive Abstract Summary    The dengue virus has become one of the most important arboviral pathogens given the recent increase in incidence in the tropics and subtropics. It is transmitted among humans, primarily by the mosquito Aedes aegypti. Dengue transmission and disease dynamics are exacerbated by the existence of four closely related dengue serotypes. Mosquito vectors are able to limit infection with certain pathogens by mounting a range of immune responses. Although great advances have been made in understanding the mosquito responses to other pathogens such as Plasmodium, little is known about the mosquito antiviral immune responses.
Our previous studies have demonstrated the implication of the Toll Pathway as part of the anti-dengue defense repertoire at 7days post-infection. In this study we have assessed the anti-dengue effectiveness of this pathway at the early stage of infection and against different dengue virus serotypes and in field-derived mosquitoes. We observed that the Toll pathway is active at the early stages of infection (72h post-infection), at the time when new virions are released from the midgut for widespread dissemination. Furthermore, this immune defense is effective against other dengue virus serotypes and present in different strains of field-derived Aedes aegypti mosquitoes. This work adds important information to our understanding of mosquito-dengue virus interactions at the early stages of infection and key factors that modulate dengue transmission. The implication of the mosquito’s innate immune system in the defense against infection was investigated through reverse genetic RNAi methodology and viral plaque assays.     
 
Poster Number    36      
Applicant Name    Debika Biswal      
Project Title    Nrf2 Protects from Dermatitis and Pneumonitis Following Thoracic Irradiation      
Descriptive Abstract Summary    Cancers of the thorax continue to account for highest number of cancer deaths in the United States. The majority of patients with thoracic malignancies receive radiation therapy as the primary form of treatment or in conjunction with chemotherapy. Of these patients, 95% experience radiation dermatitis which can result in infection and loss of function of the affected area. In addition, 20% of radiotherapy patients suffer from debilitating radiation-induced lung injury (pneumonitis and fibrosis). Thus, damage to normal tissue remains the dose-limiting factor for patients with thoracic malignancies. Radiation-induced injury to normal tissue is predominantly mediated by oxidative stress. The transcription factor Nrf2 is a master regulator of the cytoprotective environmental stress response, including the antioxidant response to oxidative stress.  We hypothesize that Nrf2 plays a critical role in protection of normal tissue from oxidative damage after thoracic radiation.  Age and sex matched Nrf2+/+ and Nrf2-/- (C57BL/6 strain) mice were irradiated with 15 Gy to the thorax region. Targeted thoracic irradiation was accomplished with a small animal irradiator that mimics clinical image-guided radiotherapy delivery in humans. Pneumonitis (airway inflammation and breathing frequency) and dermatitis (hair loss, graying and erythema) were measured after different periods of irradiation. Following thoracic irradiation, Nrf2-/- mice showed increased mortality compared to Nrf2+/+ mice. We observed that Nrf2-/- mice had significantly greater hair loss and dermatitis relative to irradiated Nrf2+/+ mice. In addition, Nrf2-/- mice showed greater pneumonitis, as measured by breathing frequency and inflammation. In conclusion, our preliminary results show that Nrf2 may protect from dermatitis and pneumonitis after thoracic irradiation. Further studies are in progress to determine whether Nrf2 protects from the development of radiation lung fibrosis and whether pharmacological activation of Nrf2 could prove to be an effective method of radioprotection of sensitive normal tissues.     

2009 Participants: Delta Omega Scientific Poster Competition

Ramya Ambikapathi Global Disease Epidemiology and Control

Whitney Austin Seeking Help for Intimate Partner Violence through Employee Assistance Programs: Understanding Women’s Experiences

Geral Baldeviano Interleukin-17 is dispensable for myocarditis but essential for the progression to dilated cardiomyopathy in a murine model

Lori Bash Defining Incident Chronic Kidney Disease in the Research Setting: The Atherosclerosis Risk in Communities (ARIC) Study

Simina Boca Analyzing the contribution of growth-promoting pathways by patient-oriented gene set analysis.

Katherine Bowerss Glutathione genes and risk of Autism Spectrum Disorders

Allison Brown In utero exposure to maternal schistosomiasis modulates both acute and memory cellular and humoral immune responses of their offspring

Brandon Brown Acceptability Survey of HPV Vaccine Among Female Sex Workers in Lima, Peru

Brandon Brown Peruvian FSWs: understanding HPV and barriers to vaccination

Talia Chalew Development of Assay to Assess Environmental Impacts of Engineered Nanoparticles on Chesapeake Bay Oysters

Carolyn Chang Predictive Value of Cord Blood Allergen-Induced T Cell Proliferation on Childhood Atopy: A Longitudinal Birth Cohort Study

Luke Chen Outbreak of Klebsiella Pneumoniae Carbapenemase Producing Organisms in a Community Hospital in Virginia

Yu-Jen Cheng Cox Models with Smooth Functional Effect of Covariates Measured with Error

Judy Choi Silica-based nanoparticle uptake and cellular response in primary microglia.

Carol Christensen Organophosphate pesticides and sex steroid hormones in NHANES III

Michael Coronado Alternative, Th2 pathway drives chronic heart disease in males following viral infection

Deidra Crews Race, Poverty and Chronic Kidney Disease: The HANDLS Study

Kristina Das Non-Communicable Disease in Latin America and Caribbean Region

Sandrah Eckel Surrogate measures of the low physical activity criterion of frailty in the Cardiovascular Health Study

Horacio Ruisenor Escudero Research Consortium on HIV/AIDS and Tuberculosis Research Agenda on HIV/AIDS

Lindsey Garver A single molecule controls an immune response influencing susceptibility of several mosquito species to human malaria parasites.

Lauren Gibbon Neighborhood Incivilities, Perceived Neighborhood Safety and Walking Behavior among Urban-Dwelling Children

Jeff Goldsmith Fitting Tubes to Medical Images

Lori Grover Measuring the Degree of Consensus Among Vision Rehabilitation Care Providers in Their Estimation of Patient Rehabilitation Potential

Elizabeth Hammond Health Disparities and Marginalization in Bosnia-Herzegovina

Christopher Harvey Nrf2- A novel target to improve host antibacterial defenses in high risk populations

Yea-Jen Hsu The role of hospital ownership in an era of emerging infectious diseases -- Taiwan’s experience during the SARS epidemic

Yea-Jen Hsu Components of physician satisfaction with care for chronically ill older patients

Chandra Jackson A Pilot Study for Neighborhoods and Health Research in Urban and Rural Chile

Chandra Jackson Correlates of Medication Non-adherence among urban African-Americans with Type 2 diabetes

Bryan James Association of Social Engagement with Brain Volumes Assessed by Structural MRI

Miranda Jones Secondhand Tobacco Smoke Exposure in Motor Vehicles

Sarah Kessler Do HIV-infected women want to discuss fertility plans with providers; and are those discussions occurring?

Elizabeth Kinter Can Patients with Schizophrenia Complete a Conjoint Analysis? Evidence from Germany

Elizabeth Kinter Identifying patient-relevant Endpoints among Individuals with Schizophrenia: An Application fo Patient CenteredHealthTechnology

Elizabeth Kinter A patient-centered approach to evaluating treatment outcomes among patients with schizophrenia in Germany: A conjoint analysis

Gabriel Lai Association of leptin with sex steroid hormones, insulin, and CRP among adult men in NHANES III

Ji Li The influence of growth patterns on risk of overweight during early childhood among a population-based longitudinal cohort in China

Wen-Hsuan Lin Influence of the Route of Administration on Humoral, Cellular and Protective Immunity Induced in Rhesus Macaques by Live Attenuated Measles Vaccine

Deepti Malhorta Decline in Nrf2-dependent proteasomal activity results in greater Endoplasmic Reticulum stress in advanced COPD lungs

Rayna Matsuno Population profiles of extra-ovarian and ovarian serous adenocarcinomas: comparisons with grade stratification

Jessica Myers Learning from near misses in medication errors: a Bayesian approach

Rebecca Nachman Use of Ambient Concentrations of PM2.5 as Surrogates for Personal Exposure in Baltimore, MD

April Neal Lead disrupts developing hippocampal neuron synapses via NMDA receptor inhibition.

Atieh Novin Risk Factors Associated with MDR-TB at the Masih Daneshvari Hospital, Tehran, Iran

Amritha Ramakrishnan Serum Cytokine Profiles after Seasonal Influenza Vaccination

Dilini Ranatunga hIL10BAC mice: A novel in vivo model for evaluating Regulation and Function of human IL-10.

Nicholas Reich Estimating incubation period distributions with coarse data

Dionne Robinson Sex Differences in Response to Influenza

Raydel Valdes Salgado An inter-laboratory comparison of nicotine in air determinations using passive nicotine monitors assembled in Mexico and the US.

Sara Schonfeld Hormonal factors and breast cancer risk in nulliparous women

Dorry Segev Age and Comorbidities Are Effect Modifiers of Gender Disparities in Renal Transplantation

Prabu Selvam Determing Potential Infectiousness using Cough Plates in Tuberculosis Endemic Settings in Peru

Kathryn Shaw The essential role lectin-glycan interactions play in the transmission biology of the malaria parasite

Shuzhen Sim Aedes aegypti cell line responses to dengue virus infection

Maroya Spalding Lipoate synthesis and lipoate scavenging are essential to P. falciparum survival

Vivian Towe Street life and drug risk behaviors associated with exchanging sex among male street children in Lahore, Pakistan</p>

Colleen Wheeler Influence of School Closure on the Incidence of Influenza among School-age Children in Arizona

Jinchun Yan Expression of stemness genes in the epithelial cells of Brown-Norway rat prostate isolated by laser capture microdisection

Hannah Yang Genetic variation in five estrogen metabolizing genes and risk of endometrial cancer

Anjie Zhen Sole copy of Z2-type human cytidine deaminase APOBEC3H has inhibitory activity against retrotransposons and HIV-1

Hong Zhu Understanding progression of ovarian cancer in US from SEER data: a semiparametric joint model for bivariate survival distribution with interval sampling

2008 Participants in Delta Omega Scientific Poster Competition

Laura Baldassar Predictors of progression from HIV-associated minor cognitive-motor disorder to HIV-associated dementia

Lori Bash Inflammation, Hemostasis and the Risk of Kidney Function Decline in the Atherosclerosis Risk in Communities (ARIC) Study

Nagesh Borse Childhood Drowning in Developing Countries _ A Neglected Research Priority

Allison Brown In utero exposure to maternal Schistosoma mansoni infection in mice modulates immune responses to vaccines in their offspring

Raquel Charles Low Adherence to Guidelines in the Laboratory Evaluation of CKD Among U.S. Physicians

Liwei Chen Alcohol Consumption and the risk of nasopharyngeal carcinoma: a systematic review

Victoria Chou Elevated Risk of Prolonged Labor with Increasing Maternal Age Among Nulliparous Women in Rural Nepal

Deidra Crews Determinants and Outcomes of Inpatient Dialysis Initiation: The CHOICE Study

Jennifer Deal Anemia and 9-Year Domain-Specific Cognitive Decline in Community-Dwelling Older Women

Lindsey Garver Silencing of an immune pathway negative regulator renders mosquitoes resistant to the human malaria parasite

Cesar Gavidia Evaluation of Nitazoxanide and Oxfendazole efficacy against Cystic Echinococcosis in naturally infected

Gabriel Lai Association of C-peptide concentration with prostate cancer incidence in a prospective cohort

Sara Lowther Use of an Oral Fluid Survey to Assess Population Immunity to Measles Virus and the Impact of HIV-1 Infection

Cynthia McOliver Recreational water contact as a risk factor for cryptosporidium exposure among persons with HIV/AIDS in Baltimore, Marlyand

Jennifer Moïsi Enhanced diagnosis of pneumococcal meningitis using the Binax NOW® S. pneumoniae immuno-chromatographic test: a multi-site study.

Alison Mondul Statin drugs and prostate specific antigen (PSA) concentration in the National Health and Nutrition Examination Survey (NHANES) 2001 _ 2004

April Neal Effects of Long Term Lead Exposure on Pre- and Post-Synaptic Protein Markers

John Pisciotta Novel antimalarial properties of an FDA approved epithelial growth factor receptor tyrosine kinase

Anna Pollack The impact of polychlorinated biphenyl exposure on the incidence of infertility and pregnancy loss

Stephanie Richard The 1918 Influenza Pandemic Experience in Japan: Age and Geographic Mortality Patterns

Hilary Schwandt Adverse Childhood Experiences and Age at First Sex in Cebu, Philippines

Tariq Shafi Thiazide-Induced Diabetes is Mediated by Potassium Depletion

David Sintasath Identification of a Novel Simian T-lymphotropic virus (STLV) Lineage in Two Monkey Species from Cameroon: High STLV Diversity at the Hunter-Primate Interface

Stephen Sozio Statins Do Not Increase Stroke Risk in Patients Initiating Dialysis: The Choices for Healthy Outcomes in Caring for End Stage Renal Disease (CHOICE) Study

Bruce Swihart The Lasagna Plot: A saucy new alternative to the Spaghetti Plot

James Williams Identifying Domain Specific Associations between Instrumental Activities of Daily Living (IADL) Disability, Cognition, & Mobility

Stella Yi Correlates of N-terminal prohormone brain natriuretic peptides (NT-proBNP) in African Americans without heart failure: the African-American Study of Kidney Disease and Hypertension (AASK)