Medicine and Health Sciences Commons^™

Maternal Psychiatric Disease And Epigenetic Evidence Suggest A Common Biology For Poor Fetal Growth, Timothy H. Ciesielski, Carmen J. Marsit, Scott M. Williams

Dartmouth Scholarship

We sought to identify and characterize predictors of poor fetal growth among variables extracted from perinatal medical records to gain insight into potential etiologic mechanisms. In this process we reevaluated a previously observed association between poor fetal growth and maternal psychiatric disease. We evaluated 449 deliveries of >36 weeks gestation that occurred between 9/2008 and 9/2010 at the Women and Infants Hospital in Providence Rhode Island. This study group was oversampled for Small-for-Gestational-Age (SGA) infants and excluded Large-for-Gestational-Age (LGA) infants. We assessed the associations between recorded clinical variables and impaired fetal growth: SGA or Intrauterine Growth Restriction (IUGR) diagnosis. After …

Cohort Of Birth Modifies The Association Between Fto Genotype And Bmi, James Niels Rosenquist, Steven F. Lehrer, A. James O'Malley, Alan M. Zaslavsky, Jordan W. Smoller, Nicholas A. Christakis

Dartmouth Scholarship

A substantial body of research has explored the relative roles of genetic and environmental factors on phenotype expression in humans. Recent research has also sought to identify gene-environment (or g-by-e) interactions, with mixed success. One potential reason for these mixed results may relate to the fact that genetic effects might be modified by changes in the environment over time. For example, the noted rise of obesity in the United States in the latter part of the 20th century might reflect an interaction between genetic variation and changing environmental conditions that together affect the penetrance of genetic influences. To evaluate this …

Sessile Serrated Adenomas In The Proximal Colon Are Likely To Be Flat, Large And Occur In Smokers, Tarun Rustagi, Priya Rangasamy, Matthew Myers, Melinda Sanders, Haleh Vaziri, George Y. Wu, John W. Birk, Petr Protiva, Joseph C. Anderson

Dartmouth Scholarship

Aim: To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs).

Methods: We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period.

Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen

Dartmouth Scholarship

Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed d population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s …

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.

Gpnn: Power Studies And Applications Of A Neural Network Method For Detecting Gene-Gene Interactions In Studies Of Human Disease, Alison A. Motsinger, Stephen L. Lee, George Mellick, Marylyn D. Ritchie

Dartmouth Scholarship

The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease.

A Critical Role For The Programmed Death Ligand 1 In Fetomaternal Tolerance, Indira Guleria, Arezou Khosroshahi, Mohammed Javeed Ansari, Antje Habicht, Miyuki Azuma, Hideo Yagita, Randolph J. Noelle

Dartmouth Scholarship

Fetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. Blockade of PDL1 signaling during murine pregnancy resulted in increased rejection rates of allogeneic concepti but not syngeneic concepti. Fetal rejection was T cell