Multistage carcinogenesis and the incidence of thyroid cancer in the US by sex, race, stage and histology

Abstract Background Thyroid cancer has the fastest growing incidence in the US. However, the underlying causes are still under debate. Methods We analyzed thyroid cancer incidence in the SEER-9 registry from 1973-2010 using multistage carcinogenesis and age-period-cohort models. Multistage models were used to investigate differences in initiation, promotion and malignant conversion rates of thyroid tumors by sex, race, stage, and histology. Models were adjusted for period and cohort trends to investigate the contributions of each factor, and determine whether birth- or diagnosis-year better correlate with observed incidence patterns. Results Significant increases in thyroid cancer incidence by period or calendar-year were found for all sex, race, stage and histology combinations, particularly for localized cases (a 3- and 4-fold increase from 1973-2010 for females and males, respectively). Multistage analyses suggest that the 3-fold higher incidence in women could be explained by 1.5-fold higher initiation and promotion rates. Analyses by race suggest that the lower incidence in blacks can be attributed to lower promotion rates versus whites. Analysis by histology showed considerable decreases in follicular cancer incidence by birth-cohort since the early 1900s. Conclusions Multistage modeling suggests that variations in thyroid cancer initiation and promotion can explain the observed differences in incidence by sex, race and histology. The consistent increases in incidence by calendar-year for all sex-race-histology-stage combinations suggest that the rise may be predominantly due to more intensive screening-diagnostics, although an environmental factor may be also at play. Our analyses constitute a first step towards the development of thyroid cancer natural history models.http://deepblue.lib.umich.edu/bitstream/2027.42/113073/1/12889_2015_Article_2108.pd

Transcriptional landscape of epithelial and immune cell populations revealed through FACS-seq of healthy human skin.

Human skin consists of multiple cell types, including epithelial, immune, and stromal cells. Transcriptomic analyses have previously been performed from bulk skin samples or from epithelial and immune cells expanded in cell culture. However, transcriptomic analysis of bulk skin tends to drown out expression signals from relatively rare cells while cell culture methods may significantly alter cellular phenotypes and gene expression profiles. To identify distinct transcriptomic profiles of multiple cell populations without substantially altering cell phenotypes, we employed a fluorescence activated cell sorting method to isolate keratinocytes, dendritic cells, CD4+ T effector cells, and CD8+ T effector cells from healthy skin samples, followed by RNA-seq of each cell population. Principal components analysis revealed distinct clustering of cell types across samples, while differential expression and coexpression network analyses revealed transcriptional profiles of individual cell populations distinct from bulk skin, most strikingly in the least abundant CD8+ T effector population. Our work provides a high resolution view of cutaneous cellular gene expression and suggests that transcriptomic profiling of bulk skin may inadequately capture the contribution of less abundant cell types

Low NOx Fuel Flexible Combustor Integration Project Overview

The Integrated Technology Demonstration (ITD) 40A Low NOx Fuel Flexible Combustor Integration development is being conducted as part of the NASA Environmentally Responsible Aviation (ERA) Project. Phase 2 of this effort began in 2012 and will end in 2015. This document describes the ERA goals, how the fuel flexible combustor integration development fulfills the ERA combustor goals, and outlines the work to be conducted during project execution

A population-based study of Kaposi Sarcoma-associated herpesvirus seropositivity in Uganda using principal components analysis

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) seropositivity is associated with sexual, environmental, and socioeconomic exposures. Whether these characteristics are independent risk factors is uncertain because of reliance on selected high-risk or hospital-based populations and incomplete adjustment for confounding. Therefore, we evaluated risk factors for KSHV seropositivity in a population-based study in Uganda using principal components analysis (PCA). METHODS: The study population comprised 2,681 individuals randomly selected from a nationally-representative population-based HIV/AIDS sero-behavioral survey conducted in 2004/05. Questionnaire and laboratory data (97 variables) were transformed into a smaller set of uncorrelated variables using PCA. Multivariable logistic regression models were fitted to estimate odds ratios and 95% confidence intervals for the association between components and KSHV seropositivity. RESULTS: Data were reduced to three principal components (PCs) labeled as Sexual behavioral, Socioeconomic, and Knowledge PCs. In crude analysis, KSHV seropositivity was associated with the Knowledge (p(trend) = 0.012) and Socioeconomic components (p(trend) = 0.0001), but not with the Sexual-behavioral component (p(trend) = 0.066). KSHV seropositivity was associated with the Socioeconomic PC (p(trend) = 0.037), but not with the Sexual-behavioral and Knowledge PCs, in the models including PCs, age, gender and geographic region. CONCLUSIONS: Our results fit with the view that in Uganda socioeconomic characteristic may influence KSHV seropositivity. Conversely, the results fit with the interpretation that in Uganda sexual-behavioral characteristics, if relevant, contribute minimally

A population-based study of Kaposi Sarcoma-associated herpesvirus seropositivity in Uganda using principal components analysis

Abstract Background Kaposi sarcoma-associated herpesvirus (KSHV) seropositivity is associated with sexual, environmental, and socioeconomic exposures. Whether these characteristics are independent risk factors is uncertain because of reliance on selected high-risk or hospital-based populations and incomplete adjustment for confounding. Therefore, we evaluated risk factors for KSHV seropositivity in a population-based study in Uganda using principal components analysis (PCA). Methods The study population comprised 2,681 individuals randomly selected from a nationally-representative population-based HIV/AIDS sero-behavioral survey conducted in 2004/05. Questionnaire and laboratory data (97 variables) were transformed into a smaller set of uncorrelated variables using PCA. Multivariable logistic regression models were fitted to estimate odds ratios and 95% confidence intervals for the association between components and KSHV seropositivity. Results Data were reduced to three principal components (PCs) labeled as Sexual behavioral, Socioeconomic, and Knowledge PCs. In crude analysis, KSHV seropositivity was associated with the Knowledge (p trend  = 0.012) and Socioeconomic components (p trend  = 0.0001), but not with the Sexual-behavioral component (p trend  = 0.066). KSHV seropositivity was associated with the Socioeconomic PC (p trend  = 0.037), but not with the Sexual-behavioral and Knowledge PCs, in the models including PCs, age, gender and geographic region. Conclusions Our results fit with the view that in Uganda socioeconomic characteristic may influence KSHV seropositivity. Conversely, the results fit with the interpretation that in Uganda sexual-behavioral characteristics, if relevant, contribute minimally.http://deepblue.lib.umich.edu/bitstream/2027.42/112399/1/13027_2012_Article_423.pd

Measurement of Trace Water Vapor in a Carbon Dioxide Removal Assembly Product Stream

The International Space Station Carbon Dioxide Removal Assembly (CDRA) uses regenerable adsorption technology to remove carbon dioxide (COP) from cabin air. Product water vapor measurements from a CDRA test bed at the NASA Marshall Space Flight Center were made using a tunable infrared diode laser differential absorption spectrometer (TILDAS) provided by NASA Glenn Research Center. The TILDAS instrument exceeded all the test specifications, including sensitivity, dynamic range, time response, and unattended operation. During the COP desorption phase, water vapor concentrations as low as 5 ppmv were observed near the peak of CO2 evolution, rising to levels of approx. 40 ppmv at the end of a cycle. Periods of high water concentration (>100 ppmv) were detected and shown to be caused by an experimental artifact. Measured values of total water vapor evolved during a single desorption cycle were as low as 1 mg

Top-Charm Associated Production in High Energy e+e−e^+e^- Collisions

The possibility of exploring the flavor changing neutral current $tcZ/tc\gamma$ couplings in the production vertex for the reaction \epem\to t\bar c + \bar tc is examined. Using a model independent parameterization for the effective Lagrangian to describe the most general three-point interactions, production cross sections are found to be relatively small at LEP II, but potentially sizeable at higher energy \epem colliders. The kinematic characteristics of the signal are studied and a set of cuts are devised for clean separation of the signal from background. The resulting sensitivity to anomalous flavor changing couplings at LEP II with an integrated luminosity of $4\times 500$ pb$^{-1}$ is found to be comparable to their present indirect constraints from loop processes, while at higher energy colliders with $0.5-1$ TeV center-of-mass energy and 50-200 fb$^{-1}$ luminosity, one expects to reach a sensitivity at or below the percentage level.Comment: Latex, 22 page

Lactate Regulates Metabolic and Proinflammatory Circuits in Control of T Cell Migration and Effector Functions

Licensed by the Creative Commons Attribution Licens

Protocol for the development of guidance for stakeholder engagement in health and healthcare guideline development and implementation

Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. METHODS: This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. DISCUSSION: We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health

Rare Charm Decays in the Standard Model and Beyond

We perform a comprehensive study of a number of rare charm decays, incorporating the first evaluation of the QCD corrections to the short distance contributions, as well as examining the long range effects. For processes mediated by the $c\to u\ell^+\ell^-$ transitions, we show that sensitivity to short distance physics exists in kinematic regions away from the vector meson resonances that dominate the total rate. In particular, we find that $D\to\pi\ell^+\ell^-$ and $D\to\rho\ell^+\ell^-$ are sensitive to non-universal soft-breaking effects in the Minimal Supersymmetric Standard Model with R-parity conservation. We separately study the sensitivity of these modes to R-parity violating effects and derive new bounds on R-parity violating couplings. We also obtain predictions for these decays within extensions of the Standard Model, including extensions of the Higgs, gauge and fermion sectors, as well as models of dynamical electroweak symmetry breaking.Comment: 45 pages, typos fixed, discussions adde