The Use of Laboratory and Agent-based Models to Evaluate the Role of Natural Transformation in Biofilms in the Formation and Spread of Antibiotic Resistant Bacteria in Water Systems.

Biofilms are aggregates of bacterial cells. Frequency of gene transfer in biofilms may be higher than in corresponding planktonic counterparts due to increased competence. Biofilms, antibiotics and antibiotic resistance determinants all occur in water systems. This dissertation assesses the role of natural transformation in biofilms in the formation and dissemination of antibiotic resistant bacteria in water networks using laboratory and agent-based models. We initially demonstrated detectable transformation frequencies in Acinetobacter baylyi strain AC811 biofilms exposed to varying genomic and donor DNA encoding antibiotic resistance in a once-through flow system replicating environmental conditions in water system pipes. Another set of experiments compared transformation frequencies of AC811 biofilm and planktonic cells and demonstrated that transformation frequencies of planktonic cells were approximately 10-fold higher than frequencies in biofilm cells. qPCR was used to quantify comP gene expression in AC811. Comparison of comP gene expression trends in biofilm and planktonic cells suggests that the observed frequency differences are due to a variation in competence state between biofilm and free-floating cells. These results suggest that the assumption of increased competence of biofilm cells as compared to planktonic cells may not be generalizable across all bacterial species. Development of an agent-based model allowed us to study additional factors that may affect transformation frequency and in a setting that allows visualization of the biofilm structure. We developed an extension to the iDynoMiCs agent-based model and used this extended model to assess the effect of resistance gene burden value on the persistence of resistant bacteria in a biofilm exposed to donor DNA and varying antimicrobial concentrations. Several trends are apparent in simulations results. Bacteria harboring no cost and low cost fitness genes will persist in the absence of selective pressure and increasing antimicrobial concentration in the influent promotes increased resistance expansion within the single-species biofilm. Results suggest that influent antimicrobial concentration can substantially affect the type and frequency of resistance genes circulating in the environment. This model can be a tool to test hypotheses that are difficult to conduct in the laboratory setting and can be used to drive future laboratory studies.PHDEpidemiological ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108719/1/lmodali_1.pd

Racial-ethnic, gender identity, and sexual orientation disparities in COVID-19-related social and health outcomes: A decomposition analysis

Despite the growing literature on racial-ethnic disparities during the pandemic, less is known about the explanatory mechanisms of these disparities and inequalities across other axes, such as gender and sexual identities. We studied the levels and sources of racial-ethnic, gender identity, and sexual minority disparities in social (i.e., unmet resource needs) and health (i.e., hospitalization) outcomes among individuals diagnosed with COVID-19, hypothesizing differential age structure, underlying health, and work and living arrangements as contributors to inequalities. Using large-scale administrative data from Chicago and adjusting for covariates, we found substantial racial-ethnic and gender identity disparities in both outcomes, and weak evidence of sexual minority disparities in unmet needs. Subsequent decomposition analyses revealed that living in larger households, having a higher share of non-adult cases, and facing higher burdens of chronic illness, obesity, and unemployment each statistically significantly drove racial-ethnic disparities in unmet needs, but these together explained less than 15% of the disparities. Similarly, about 20% of the Black-White gap in hospitalization resulted from disparities in underlying health and unemployment, whereas a higher proportion of non-adult cases or higher unemployment rates respectively proved the only significant pathways to partially explain transgender individuals’ disadvantages in unmet needs (12%) or hospitalization (6%). These findings highlight the importance of considering multiple dimensions of social differences in studying health disparities, the vulnerabilities of transgender and non-adult communities during the pandemic, and the valid yet quite limited roles of previously suggested sociodemographic factors in accounting for COVID-19-related categorical inequalities

Abstract 2765: Evaluation of family history of cancer in first-degree relatives and increased cancer risk: A multinational study

Abstract Family history of cancer is a known risk factor for several of the more prevalent cancer types. However, familial aggregation of cancer may not follow the genetic linkage pattern seen with most inherited cancer syndromes. In these instances, clustering may be due to unknown hereditary genetic mutations or to an aggregation of environmental risk factors and such clustering may still confer a significant risk. We assessed the association between family history of cancer in first-degree relatives and cancer risk among 9,122 cancer cases and 76,537 controls in a multinational study. Analyses also included evaluation of breast, colon and prostate cancer risk associated with family history of these respective cancer types. Cases were verified by physician diagnosis and all study participants were administered an in-depth survey to ascertain various demographic and lifestyle factors as well as a complete family history of cancer among first-degree relatives. Multivariable logistic regression was used to assess the association between family history of cancer and cancer risk. Among all subjects, the odds ratio (OR) for individuals with a family history of cancer was 1.79 [95% confidence interval = 1.7-1.9] after adjusting for age, gender, BMI, smoking pack years and ethnicity. Additionally, a greater cancer risk was associated with increasing number of first-degree relatives with a history of cancer. Ethnic groups studied included Caucasian-Americans, African-Americans, Hispanic/Latinas and Caucasian-Polish. All ethnic groups showed a significant association between family history of cancer and cancer risk with the highest adjusted OR of 2.65 [95% confidence interval = 2.0-3.6] among the Hispanic/Latina group. Further analyses indicated that family history of colon, breast and prostate cancer was significantly associated with an increased risk of these respective cancer types across studied ethnic groups. In particular, the adjusted ORs for breast, colon and prostate cancer risk in the Caucasian-Polish group were at least double the overall adjusted ORs for each cancer type. Our study shows that family history of cancer is a significant predictor of cancer risk especially among certain ethnic groups. In addition, family history of cancer can represent both a genetic predisposition and/or environmental exposure and risk associated with familial clustering of cancer. Citation Format: Laxmi Modali, Teresa A. Lehman, Ramakrishna Modali, Luke D. Ratnasinghe. Evaluation of family history of cancer in first-degree relatives and increased cancer risk: A multinational study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2765. doi:10.1158/1538-7445.AM2015-2765</jats:p

Teaching Residents to Work with Torture Survivors: Experiences from the Bronx Human Rights Clinic

INTRODUCTION: Despite the 1984 United Nations\u27s Convention Against Torture calling to train doctors to work with torture survivors, many physicians are unaware of their obligation and few are taught the requisite clinical skills. AIM: To describe the development, implementation, and evaluation of a curriculum to teach residents to work with torture survivors. PARTICIPANTS: Medicine residents in New York City PROGRAM DESCRIPTION: A 2-component curriculum consisting of a series of workshops and clinical experiences, which provide content, skills, and practices regarding the medical, psychological, ethical, and legal aspects of evaluating and caring for torture survivors. CURRICULUM EVALUATION: All 22 trainees received surveys before and after training. Surveys assessed residents\u27 relevant prior experience, beliefs, skills, and attitudes regarding working with torture survivors. At baseline, 23% of residents described previous human rights trainings and 17% had work experiences with torture survivors. Before the curriculum, 81% of residents reported doctors should know how to evaluate survivors, although only 5% routinely screened patients for torture. After the curriculum, residents reported significant improvements in 3 educational domains-general knowledge, sequelae, and self-efficacy to evaluate torture survivors. DISCUSSION: This curriculum addresses the disparity between doctors\u27 obligations, and training to work with torture survivors. It is likely to achieve its educational goals, and can potentially be adapted to other residencies. © 2008 Society of General Internal Medicine