The Effects of Anthropometry and Angiogenesis on Breast Cancer Etiology

Factors such as mammographic breast density and angiogenesis may be related to breast cancer development, though numerous questions about the etiologic mechanisms remain. Percent density is positively associated with breast cancer risk, yet is negatively associated with another breast cancer risk factor, body mass index (BMI). Vascular endothelial growth factor (VEGF) is a primary regulator of angiogenesis, yet its relationship to breast cancer risk is unclear. We evaluated the longitudinal association between BMI and breast density in the Study of Women's Health Across the Nation (SWAN) Mammographic Density Substudy (N=834). Using adjusted random intercept models, changes in BMI were not associated with changes in dense breast area (Beta=-0.0105, p=0.34), but were strongly negatively associated with changes in percent density (Beta=-1.18, p<0.001). Thus, effects of changes in anthropometry on percent breast density may reflect effects on non-dense tissue, rather than on the dense tissue where cancers arise. Breast density was measured from routine screening mammograms which were not timed with SWAN visits. We developed a method to align the off-schedule mammogram data to the study visit times using linear interpolation with multiple imputation. Our method was shown to be valid, with an average bias for dense breast area of 0.11 cm2. In the random intercept models, use of a simple matching algorithm to estimate breast density produced different (Beta=-0.0155, p=0.04), and likely incorrect, results. Our linear interpolation with multiple imputations method may be applicable to other longitudinal datasets with important data collected off-schedule. In a separate case-control study, the Mammograms and Masses Study (MAMS), we evaluated the association between serum VEGF levels and breast cancer (N=407). Geometric mean VEGF levels were higher among cases (331.4 pg/mL) than controls (291.4 pg/mL; p=0.21). In a multivariable logistic regression model, VEGF greater than or equal to 314.2 pg/mL was positively associated with breast cancer (odds ratio 1.37, 95% confidence interval 0.88-2.12), albeit non-significantly. Higher levels of VEGF may increase breast cancer risk. We have identified roles for anthropometry and angiogenesis in breast carcinogenesis. Enhancing knowledge of breast cancer etiology is a significant contribution to public health and may lead to improved opportunities for prevention or early detection

NUMERICAL ANALYSIS OF A COMPOSITE STEEL BOX GIRDER BRIDGE IN FIRE

Box girder bridges are becoming more common because of their ease of construction, pleasing appearance, and serviceability. Projects with curved configuration and long spans can especially benefit from these advantages. However, the industry lacks a wide range of research on multi-span steel box girder cross-sections and their response to fire events. This poses a major risk to unprotected steel bridges using a box girder design. This paper will discuss a mathematical approach to determining and classifying different failure modes of weathering steel box girder bridges subject to two fire cases. Due to the rapid increase of temperature in the thin steel members, the strength of the steel deteriorates quickly. Results show that different fire locations can greatly affect the forces that act on the individual members of the structure

Evaluating lithium diffusion mechanisms in the complex spinel Li2NiGe3O8

Lithium-ion diffusion mechanisms in the complex spinel Li2NiGe3O8 have been investigated using solid-state NMR, impedance, and muon spectroscopies. Partial occupancy of migratory interstitial 12d sites is shown to occur at lower temperatures than previously reported. Bulk activation energies for Li+ ion hopping range from 0.43 ± 0.03 eV for powdered samples to 0.53 ± 0.01 eV for samples sintered at 950 °C for 24 h, due to the loss of Li during sintering at elevated temperatures. A lithium diffusion coefficient of 3.89 × 10−12 cm2 s−1 was calculated from muon spectroscopy data for Li2NiGe3O8 at 300 K

A long, hard look at MCG-6-30-15 with XMM-Newton II: detailed EPIC analysis and modelling

The bright Seyfert 1 galaxy MCG-6-30-15 has provided some of the best evidence to date for the existence of supermassive black holes in active galactic nuclei. Observations with ASCA revealed an X-ray iron line profile shaped by strong Doppler and gravitational effects. In this paper the shape of the iron line, its variability characteristics and the robustness of this spectral interpretation are examined using the long XMM-Newton observation taken in 2001. A variety of spectral models, both including and excluding the effects of strong gravity, are compared to the data in a uniform fashion. The results strongly favour models in which the spectrum is shaped by emission from a relativistic accretion disc. It is far more difficult to explain the 3-10 keV spectrum using models dominated by absorption (either by warm or partially covering cold matter), emission line blends, curved continua or additional continuum components. These provide a substantially worse fit to the data and fail to explain other observations (such as the simultaneous BeppoSAX spectrum). This reaffirms the veracity of the relativistic `disc line' interpretation. The short term variability in the shape of the energy spectrum is investigated and explained in terms of a two-component emission model. Using a combination of spectral variability analyses the spectrum is successfully decomposed into a variable power-law component (PLC) and a reflection dominated component (RDC). The former is highly variable while the latter is approximately constant throughout the observation, leading to the well-known spectral variability patterns. (Abridged)Comment: 25 pages. 24 figures. Accepted for publication in MNRA

Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study

BACKGROUND: The etiology and pathophysiology of chronic fatigue syndrome (CFS) remain inchoate. Attempts to elucidate the pathophysiology must consider sleep physiology, as unrefreshing sleep is the most commonly reported of the 8 case-defining symptoms of CFS. Although published studies have consistently reported inefficient sleep and documented a variable occurrence of previously undiagnosed primary sleep disorders, they have not identified characteristic disturbances in sleep architecture or a distinctive pattern of polysomnographic abnormalities associated with CFS. METHODS: This study recruited CFS cases and non-fatigued controls from a population based study of CFS in Wichita, Kansas. Participants spent two nights in the research unit of a local hospital and underwent overnight polysomnographic and daytime multiple sleep latency testing in order to characterize sleep architecture. RESULTS: Approximately 18% of persons with CFS and 7% of asymptomatic controls were diagnosed with severe primary sleep disorders and were excluded from further analysis. These rates were not significantly different. Persons with CFS had a significantly higher mean frequency of obstructive apnea per hour (p = .003); however, the difference was not clinically meaningful. Other characteristics of sleep architecture did not differ between persons with CFS and controls. CONCLUSION: Although disordered breathing during sleep may be associated with CFS, this study generally did not provide evidence that altered sleep architecture is a critical factor in CFS. Future studies should further scrutinize the relationship between subjective sleep quality relative to objective polysomnographic measures

Restored Agricultural Wetlands in central Iowa: Habitat Quality and Amphibian Response

Amphibians are declining throughout the United States and worldwide due, partly, to habitat loss. Conservation practices on the landscape restore wetlands to denitrify tile drainage effluent and restore ecosystem services. Understanding how water quality, hydroperiod, predation, and disease affect amphibians in restored wetlands is central to maintaining healthy amphibian populations in the region. We examined the quality of amphibian habitat in restored wetlands relative to reference wetlands by comparing species richness, developmental stress, and adult leopard frog (Lithobates pipiens) survival probabilities to a suite of environmental metrics. Although measured habitat variables differed between restored and reference wetlands, differences appeared to have sub-lethal rather than lethal effects on resident amphibian populations. There were few differences in amphibian species richness and no difference in estimated survival probabilities between wetland types. Restored wetlands had more nitrate and alkaline pH, longer hydroperiods, and were deeper, whereas reference wetlands had more amphibian chytrid fungus zoospores in water samples and resident amphibians exhibited increased developmental stress. Restored and reference wetlands are both important components of the landscape in central Iowa and maintaining a complex of fish-free wetlands with a variety of hydroperiods will likely contribute to the persistence of amphibians in this landscape

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation. NKs were screened for FcγRIIIa (human) and FcγRIII (RM) genotypes (FcγRIII(a)), receptor signaling, and antibody-dependent cellular cytotoxicity (ADCC), the latter mediated by a cocktail of monoclonal IgG1 antibodies with human or RM Fc. FcγRIII(a) genetic polymorphisms alone did not explain differences in NK effector functionality in either species cohort. Using the same parameters, hierarchical clustering separated each species into two clusters. Importantly, in principal components analyses, ADCC magnitude, NK contribution to ADCC, FcγRIII(a) cell-surface expression, and frequency of phosphorylated CD3ζ NK cells all contributed similarly to the first principal component within each species, demonstrating the importance of measuring multiple facets of NK cell function. Although ADCC potency was similar between species, we detected significant differences in frequencies of NK cells and pCD3ζ+ cells, level of cell-surface FcγRIII(a) expression, and NK-mediated ADCC (P&lt;0.001), indicating that a combination of Fc-FcR parameters contribute to overall inter-species functional differences. These data strongly support the importance of multi-parameter analyses of Fc-FcR NK-mediated functions when evaluating efficacy of passive and active immunizations in pre- and clinical trials and identifying correlates of protection. The results also suggest that pre-screening animals for multiple FcR-mediated NK function would ensure even distribution of animals among treatment groups in future preclinical trials