Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer.

BACKGROUND: We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS), a population-based, case-control study. METHODS/PRINCIPAL FINDINGS: The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, non-Hispanic race. Statistical analysis was two staged: a screen using marginal Bayes factors (BFs) for 484 SNPs and a modeling stage in which we calculated multivariate adjusted posterior probabilities of association for 77 SNPs that passed the screen. These probabilities were conditional on subject age at diagnosis/interview, batch, a DNA quality metric and genotypes of other SNPs and allowed for uncertainty in the genetic parameterizations of the SNPs and number of associated SNPs. Six SNPs had Bayes factors greater than 10 in favor of an association with invasive serous ovarian cancer. These included rs5762746 (median OR(odds ratio)(per allele) = 0.66; 95% credible interval (CI) = 0.44-1.00) and rs6005835 (median OR(per allele) = 0.69; 95% CI = 0.53-0.91) in CHEK2, rs2078486 (median OR(per allele) = 1.65; 95% CI = 1.21-2.25) and rs12951053 (median OR(per allele) = 1.65; 95% CI = 1.20-2.26) in TP53, rs411697 (median OR (rare homozygote) = 0.53; 95% CI = 0.35 - 0.79) in BACH1 and rs10131 (median OR( rare homozygote) = not estimable) in LIG4. The six most highly associated SNPs are either predicted to be functionally significant or are in LD with such a variant. The variants in TP53 were confirmed to be associated in a large follow-up study. CONCLUSIONS/SIGNIFICANCE: Based on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results.

Internal languages of retrieval: the bilingual encoding of memories for the personal past.

In contrast to most research on bilingual memory that focuses on how words in either lexicon are mapped onto memory for objects and concepts, we focus on memory for events in the personal past. Using a word-cue technique in sessions devoted exclusively to one language, we found that older Hispanic immigrants who had come to the United States as adults internally retrieved autobiographical memories in Spanish for events in the country of origin and in English for events in the U.S. These participants were consistently capable of discerning whether a memory had come to them "in words" or not, reflecting the distinction between purely imagistic or conceptual memories and specifically linguistic memories. Via examination of other phenomenological features of these memories (sense of re-living, sensory detail, emotionality, and rehearsal), we conclude that the linguistic/nonlinguistic distinction is fundamental and independent of these other characteristics. Bilinguals encode and retrieve certain autobiographical memories in one or the other language according to the context of encoding, and these linguistic characteristics are stable properties of those memories over time.

Essays on the Dynamic Decisions of Homeowners and Retailers

Urban problems have several features that make them inherently dynamic. Large transaction costs all but guarantee that homeowners will do their best to consider how a neighborhood might change before buying a house. Similarly, stores face large sunk costs when opening, and want to be sure that their investment will pay off in the long run. In line with those concerns, different areas of Economics have made recent advances in modeling those questions within a dynamic framework. This dissertation contributes to those efforts.

Chapter 2 discusses how to model an agent’s location decision when the agent must learn about an exogenous amenity that may be changing over time. The model is applied to estimating the marginal willingness to pay to avoid crime, in which agents are learning about the crime rate in a neighborhood, and the crime rate can change in predictable (Markovian) ways.

Chapters 3 and 4 concentrate on location decision problems when there are externalities between decision makers. Chapter 3 focuses on the decision of business owners to open a store, when its demand is a function of other nearby stores, either through competition, or through spillovers on foot traffic. It uses a dynamic model in continuous time to model agents’ decisions. A particular challenge is isolating the contribution of spillovers from the contribution of other unobserved neighborhood attributes that could also lead to agglomeration. A key contribution of this chapter is showing how we can use information on storefront ownership to help separately identify spillovers.

Finally, chapter 4 focuses on a class of models in which families prefer to live

close to similar neighbors. This chapter provides the first simulation of such a model in which agents are forward looking, and shows that this leads to more segregation than it would have been observed with myopic agents, which is the standard in this literature. The chapter also discusses several extensions of the model that can be used to investigate relevant questions such as the arrival of a large contingent high skilled tech workers in San Francisco, the immigration of hispanic families to several southern American cities, large changes in local amenities, such as the construction of magnet schools or metro stations, and the flight of wealthy residents from cities in the Rust belt, such as Detroit.