Determinants of mammographic breast density by race among a large screening population

Background: Because of the mixed reports from smaller studies, we examined associations of race with mammographic breast density and evaluated racial differences in the determinants of breast density. Methods: Participants included 37 839 women (23 166 non-Hispanic white and 14 673 African American) receiving screening mammograms at the Joanne Knight Breast Health Center at Washington University School of Medicine from June 2010 to December 2015. Mammographic breast density was assessed using the Breast Imaging Reporting and Data System (5th edition). To determine the association of race and participant characteristics with mammographic breast density, we used multivariable polytomous logistic regression models (reference group: almost entirely fatty). Results: African American women had increased odds of extremely dense (adjusted odds ratio = 1.31, 95% confidence interval = 1.13 to 1.52) and reduced odds of heterogeneously dense breasts (adjusted odds ratio = 0.91, 95% confidence interval = 0.84 to 0.99) compared with non-Hispanic white women. Altogether, race, parity and age at first birth, current age, current body mass index (BMI), BMI at age 18 years, menarche, family history of breast cancer, oral contraceptive use, alcohol use, and menopausal status explained 33% of the variation in mammographic breast density. Among African American and non-Hispanic white women, these factors explained nearly 28.6% and 33.6% of the variation in mammographic density, respectively. Current BMI provided the greatest explanation of breast density (26.2% overall, 22.2% in African American, and 26.2% in non-Hispanic white women). Conclusions: The determinants of mammographic breast density were generally similar between African American women and non-Hispanic white women. After adjustments for confounders, African Americans had higher likelihood of extremely dense breasts but lower likelihood of heterogeneously dense breasts. The greatest explanation of breast density was provided by BMI, regardless of race

Association of baseline inflammatory biomarkers with cancer mortality in the REGARDS cohort

This study examines the association between inflammatory biomarkers and risk of cancer mortality by race. Data were obtained from 1,856 participants in the prospective REGARDS cohort who were cancer-free at baseline, and analyzed in relation to cancer mortality prospectively. Biomarkers were log-transformed and categorized into tertiles due to non-normal distributions, and Cox proportional hazard regression models were utilized to compute hazard ratios with 95% confidence intervals using robust sandwich methods. Individuals in the highest tertile of IL-6 had over a 12-fold increased risk of cancer mortality (HR: 12.97, 95% CI: 3.46-48.63); those in the highest tertile of IL-8 had over a 2-fold increased risk of cancer mortality (HR: 2.21, 95% CI: 0.86-5.71), while those in the highest tertile of IL-10 had over a 3-fold increased risk of cancer mortality (HR: 3.06, 95% CI: 1.35-6.89). In race-stratified analysis, each unit increase in IL-6 was associated with increased risk of cancer mortality among African-Americans (HR: 3.88, 95% CI: 1.17-12.88) and Whites (5.25, 95% CI: 1.24-22.31). If replicated in larger, racially diverse prospective cohorts, these results suggest that cancer patients may benefit from clinical or lifestyle approaches to regulate systemic inflammation as a cancer prevention strategy

The role of BMI in allostatic load and risk of cancer death

INTRODUCTION: Obesity and proinflammatory conditions are associated with increased risks of cancer. The associations of baseline allostatic load with cancer mortality and whether this association is modified by body mass index (BMI) were examined. METHODS: A retrospective analysis was performed in March-September 2022 using National Health and Nutrition Examination Survey years 1988 through 2010 linked with the National Death Index through December 31, 2019. Fine and Gray Cox proportional hazard models were stratified by BMI status to estimate subdistribution hazard ratios of cancer death between high and low allostatic load status (adjusted for age, sociodemographics, and health factors). RESULTS: In fully adjusted models, high allostatic load was associated with a 23% increased risk of cancer death (adjusted subdistribution hazard ratio=1.23; 95% CI=1.06, 1.43) among all participants, a 3% increased risk of cancer death (adjusted subdistribution hazard ratio=1.03; 95% CI=0.78, 1.34) among underweight/healthy weight adults, a 31% increased risk of cancer death (adjusted subdistribution hazard ratio=1.31; 95% CI=1.02, 1.67) among overweight adults, and a 39% increased risk of death (adjusted subdistribution hazard ratio=1.39; 95% CI=1.04, 1.88) among obese adults, when compared to those with low allostatic load. CONCLUSIONS: The risk of cancer death is highest among those with high allostatic load and obese BMI, but this effect was attenuated among those with high allostatic load and underweight/healthy or overweight BMI

Infra-Red Stable Supersymmetry in Chern-Simons Theories with Matter and Quenched Disorder

We study Abelian Chern-Simons field theories with matter fields and global SU(N) symmetry in the presence of random weak quenched disorder. In the absence of disorder these theories possess N=2 supersymmetric fixed points and N=1 supersymmetric fixed lines in the infra-red limit. We show that although the presence of disorder forbids any supersymmetry of the bare action, infra-red stable supersymmetric fixed points and fixed lines are realized in the disorder-averaged effective theories.Comment: 8 pp., LaTeX. Explanatory remarks and references added. Version to appear in Phys. Rev. Let

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Merging Resource Availability with Isotope Mixing Models: The Role of Neutral Interaction Assumptions

Background: Bayesian mixing models have allowed for the inclusion of uncertainty and prior information in the analysis of trophic interactions using stable isotopes. Formulating prior distributions is relatively straightforward when incorporating dietary data. However, the use of data that are related, but not directly proportional, to diet (such as prey availability data) is often problematic because such information is not necessarily predictive of diet, and the information required to build a reliable prior distribution for all prey species is often unavailable. Omitting prey availability data impacts the estimation of a predator's diet and introduces the strong assumption of consumer ultrageneralism (where all prey are consumed in equal proportions), particularly when multiple prey have similar isotope values. Methodology: We develop a procedure to incorporate prey availability data into Bayesian mixing models conditional on the similarity of isotope values between two prey. If a pair of prey have similar isotope values (resulting in highly uncertain mixing model results), our model increases the weight of availability data in estimating the contribution of prey to a predator's diet. We test the utility of this method in an intertidal community against independently measured feeding rates. Conclusions: Our results indicate that our weighting procedure increases the accuracy by which consumer diets can be inferred in situations where multiple prey have similar isotope values. This suggests that the exchange of formalism for predictive power is merited, particularly when the relationship between prey availability and a predator's diet cannot be assumed for all species in a system.National Science Foundation (NSF) [DEB-0608178]U.S. Environmental Protection AgencyDepartment of EducationSigma XiUniversity of ChicagoFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)(CAPES) Coordenacao de Aperfeicoamento de Pessoal de Nivel Superiori

CD14 Signaling Restrains Chronic Inflammation through Induction of p38-MAPK/SOCS-Dependent Tolerance

Current thinking emphasizes the primacy of CD14 in facilitating recognition of microbes by certain TLRs to initiate pro-inflammatory signaling events and the importance of p38-MAPK in augmenting such responses. Herein, this paradigm is challenged by demonstrating that recognition of live Borrelia burgdorferi not only triggers an inflammatory response in the absence of CD14, but one that is, in part, a consequence of altered PI3K/AKT/p38-MAPK signaling and impaired negative regulation of TLR2. CD14 deficiency results in increased localization of PI3K to lipid rafts, hyperphosphorylation of AKT, and reduced activation of p38. Such aberrant signaling leads to decreased negative regulation by SOCS1, SOCS3, and CIS, thereby compromising the induction of tolerance in macrophages and engendering more severe and persistent inflammatory responses to B. burgdorferi. Importantly, these altered signaling events and the higher cytokine production observed can be mimicked through shRNA and pharmacological inhibition of p38 activity in CD14-expressing macrophages. Perturbation of this CD14/p38-MAPK-dependent immune regulation may underlie development of infectious chronic inflammatory syndromes

The Earth: Plasma Sources, Losses, and Transport Processes

This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed