bluuebunny/crossref_metadata_2025 huggingface dataset:
Commodity Prices over Two Centuries: Trends, Volatility, and Impact
Authors: Williamson Jeffrey G.
Published: June 2012

Does trade raise growth rates of commodity exporters less than those of industrial goods exporters? Do industrial countries gain more from trade? Do world trade booms over the past two centuries help account for the widening gap between rich and poor countries because of some asymmetric growth impact? These old questions can now be answered with hard evidence, and the answer is yes to all three. World trade booms have always been associated with commodity price booms and thus with terms-of-trade improvements favoring the commodity exporter. But whereas commodity exporters' GDP levels increased—that is, they gained from trade—their growth rates either did not increase or increased by much less than did rates of their industrial trading partners. This survey reports these results for the period 1800–1939, but it also shows how this so-called resource curse history has changed in recent decades.
(The Economics of) Discounting: Unbalanced Growth, Uncertainty, and Spatial Considerations
Authors: Sterner Thomas , Kyriakopoulou Efthymia
Published: June 2012

The economics of climate change and the various measures that should be implemented to reduce future damages are highly tied to the use of cost-benefit analysis. Traditional approaches ignore the fact that environmental amenities do not experience the same growth rate as do most of the sectors in the economy, which leads to changing relative prices. Uncertainty should also be considered, especially when one is conducting cost-benefit analysis involving the long-run damages from climate change. This article reviews some theoretical approaches to the economics of discounting and discusses issues associated with unbalanced growth, uncertainty, and spatial discounting.
Environmental Tax Reform: Principles from Theory and Practice
Authors: Parry Ian W.H. , Norregaard John , Heine Dirk
Published: June 2012

On the basis of the environmental tax literature, this article recommends a system of upstream taxes on fossil fuels, combined with refunds for downstream emissions capture, to reduce carbon and local pollution emissions. Motor fuel taxes should also account for congestion and other externalities associated with vehicle use, at least until mileage-based taxes are widely introduced. An examination of existing energy/environmental tax systems in Germany, Sweden, Turkey, and Vietnam suggests that there is substantial scope for policy reform. Policy options include harmonizing taxes for pollution content across different fuels and end users, better aligning tax rates with (albeit crude) values for externalities, and scaling back excise taxes on vehicle ownership and electricity use that are redundant (on environmental grounds) in the presence of more targeted taxes.
Including Jobs in Benefit-Cost Analysis
Authors: Bartik Timothy J.
Published: June 2012

Public policies may affect employment by directly creating jobs or facilitating job creation. In labor markets with high unemployment, such employment changes may have significant net efficiency benefits, which should be included in benefit-cost analyses. The research literature offers diverse recommendations on measuring employment benefits. Many of the recommendations rely on arbitrary assumptions. The resulting employment benefit estimates vary widely. This article reviews this literature and offers recommendations on how to better measure employment benefits using estimable parameters. Guidance is provided on measuring policy-induced labor demand, estimating the demand shock's impact on labor market outcomes, and translating labor market impacts into efficiency benefits. Two measures are proposed for efficiency benefits, one relying on adjusted reservation wage gains and the other relying on adjusted earnings gains.
Measuring Indirect Land Use Change with Biofuels: Implications for Policy
Authors: Khanna Madhu , Crago Christine L.
Published: June 2012

The indirect land use change (ILUC) effect of biofuels has called into question the greenhouse gas (GHG) mitigation benefit of biofuels compared with that of fossil fuels. This article reviews the various economic modeling approaches being used to assess the ILUC effect and discusses the key factors that influence estimates of its magnitude. We find that there is considerable variability in the magnitude of ILUC associated with a biofuel pathway across studies and within a study, depending on underlying model parameters. These estimates are sensitive to the scale of biofuel production, the mix of policies and biofuels considered, variations in the parametric assumptions that govern price transmission through international trade, and the ease of changes in land use at the intensive and extensive margins. We discuss the challenges in implementing policies to address ILUC.
International Trade in Natural Resources: Practice and Policy
Authors: Ruta Michele , Venables Anthony J.
Published: June 2012

Natural resources account for 20% of world trade and dominate the exports of many countries. Policy is used to manipulate both international and domestic prices of resources, yet policy is largely outside the disciplines of the WTO. The instruments used include export taxes, price controls, production quotas, and domestic producer and consumer taxes (equivalent to trade taxes if no domestic production is possible). We review the literature and argue that the policy equilibrium is inefficient. This inefficiency is exacerbated by market failure in long-run contracts for the exploration and development of natural resources. Properly coordinated policy reforms offer an avenue to resource-exporting and resource-importing countries to overcome these inefficiencies and to obtain mutual gains.
On the Value of Agricultural Biodiversity
Authors: Di Falco Salvatore
Published: June 2012

Crop biodiversity is very important for both the functioning of ecological systems and the generation of a vast array of ecosystem services. More agricultural biodiversity is associated with higher agriculture production and lower risk exposure. This article explores the recent contributions on the economics of agrobiodiversity. The focus is (mostly) on the empirical literature. Future issues are also highlighted.
Behavioral Economics and Environmental Policy
Authors: Carlsson Fredrik , Johansson-Stenman Olof
Published: June 2012

This article provides an interpretive survey on implications of insights from behavioral economics for environmental policy. In particular, it discusses whether, and if so how, policy implications based on conventional economic theory have to be modified when insights from behavioral economics are considered. More specifically, it discusses concerns for cooperation, fairness, self-image, social approval, and status. Moreover, it addresses potential crowding-out effects, context-dependent and incoherent preferences, risk misperceptions, ambiguity aversion, and regulator bias. We conclude that behavioral economics has a lot to offer environmental economics and that some normative policy recommendations have to be modified. Yet the most fundamental policy recommendations in environmental economics generally prevail and are sometimes even reinforced through behavioral economics insights.
The New Fisheries Economics: Incentives Across Many Margins
Authors: Smith Martin D.
Published: June 2012

New research in fisheries economics addresses incentives across many margins. These margins include within-season effects, incentives to harvest different ages and sizes of fish, responses to ecological disturbances, spatial choices, and multispecies interactions. Even developments in global seafood markets are relevant for understanding contemporary fisheries management. What connects this diverse literature is the attempt to align incentives of harvesters with the objectives of optimal management and reflections on when delineating policy instruments along particular margins is worthwhile. This theme echoes the older fisheries bioeconomic literature that first identified the commons problem and proposed solutions to it using an elegant but now principally metaphorical model of a single stock.
Inhibition of intercellular coupling stabilizes spiral-wave reentry, whereas enhancement of the coupling destabilizes the reentry in favor of early termination
Authors: Takemoto Yoshio , Takanari Hiroki , Honjo Haruo , Ueda Norihiro , Harada Masahide , Kato Sara , Yamazaki Masatoshi , Sakuma Ichiro , Opthof Tobias , Kodama Itsuo , Kamiya Kaichiro
Published: June 2012

Spiral-wave (SW) reentry is a major organizing principle of ventricular tachycardia/fibrillation (VT/VF). We tested a hypothesis that pharmacological modification of gap junction (GJ) conductance affects the stability of SW reentry in a two-dimensional (2D) epicardial ventricular muscle layer prepared by endocardial cryoablation of Langendorff-perfused rabbit hearts. Action potential signals were recorded and analyzed by high-resolution optical mapping. Carbenoxolone (CBX; 30 μM) and rotigaptide (RG, 0.1 μM) were used to inhibit and enhance GJ coupling, respectively. CBX decreased the space constant (λ) by 36%, whereas RG increased it by 22–24% ( n = 5; P < 0.01). During centrifugal propagation, there was a linear relationship between the wavefront curvature (κ) and local conduction velocity (LCV): LCV = LCV0 − D·κ (D, diffusion coefficient; LCV0, LCV at κ = 0). CBX decreased LCV0 and D by 27 ± 3 and 57 ± 3%, respectively ( n = 5; P < 0.01). RG increased LCV0 and D by 18 ± 3 and 54 ± 5%, respectively ( n = 5, P < 0.01). The regression lines with and without RG crossed, resulting in a paradoxical decrease of LCV with RG at κ > ∼60 cm−1. SW reentry induced after CBX was stable, and the incidence of sustained VTs (>30 s) increased from 38 ± 4 to 85 ± 4% after CBX ( n = 18; P < 0.01). SW reentry induced after RG was characterized by decremental conduction near the rotation center, prominent drift and self-termination by collision with the anatomical boundaries, and the incidence of sustained VTs decreased from 40 ± 5 to 17 ± 6% after RG ( n = 13; P < 0.05). These results suggest that decreased intercellular coupling stabilizes SW reentry in 2D cardiac muscle, whereas increased coupling facilitates its early self-termination.
Mitochondrial Roles and Cytoprotection in Chronic Liver Injury
Authors: Degli Esposti Davide , Hamelin Jocelyne , Bosselut Nelly , Saffroy Raphaël , Sebagh Mylène , Pommier Alban , Martel Cécile , Lemoine Antoinette
Published: June 2012

The liver is one of the richest organs in terms of number and density of mitochondria. Most chronic liver diseases are associated with the accumulation of damaged mitochondria. Hepatic mitochondria have unique features compared to other organs' mitochondria, since they are the hub that integrates hepatic metabolism of carbohydrates, lipids and proteins. Mitochondria are also essential in hepatocyte survival as mediator of apoptosis and necrosis. Hepatocytes have developed different mechanisms to keep mitochondrial integrity or to prevent the effects of mitochondrial lesions, in particular regulating organelle biogenesis and degradation. In this paper, we will focus on the role of mitochondria in liver physiology, such as hepatic metabolism, reactive oxygen species homeostasis and cell survival. We will also focus on chronic liver pathologies, especially those linked to alcohol, virus, drugs or metabolic syndrome and we will discuss how mitochondria could provide a promising therapeutic target in these contexts.
BAY 11-7082 Is a Broad-Spectrum Inhibitor with Anti-Inflammatory Activity against Multiple Targets
Authors: Lee Jaehwi , Rhee Man Hee , Kim Eunji , Cho Jae Youl
Published: June 2012

BAY 11-7082 (BAY) is an inhibitor ofκB kinase (IKK) that has pharmacological activities that include anticancer, neuroprotective, and anti-inflammatory effects. In this study, BAY-pharmacological target pathways were further characterized to determine how this compound simultaneously suppresses various responses. Primary and cancerous (RAW264.7 cells) macrophages were activated by lipopolysaccharide, a ligand of toll-like receptor 4. As reported previously, BAY strongly suppressed the production of nitric oxide, prostaglandin E2, and tumor necrosis factor-αand reduced the translocation of p65, major subunit of nuclear factor-κB, and its upstream signaling events such as phosphorylation of IκBα, IKK, and Akt. In addition, BAY also suppressed the translocation and activation of activator protein-1, interferon regulatory factor-3, and signal transducer and activator of transcription-1 by inhibiting the phosphorylation or activation of extracellular signal-related kinase, p38, TANK-binding protein, and Janus kinase-2. These data strongly suggest that BAY is an inhibitor with multiple targets and could serve as a lead compound in developing strong anti-inflammatory drugs with multiple targets in inflammatory responses.
Development and Clinical Application of a Precise Temperature-Control Device as an Alternate for Conventional Moxibustion Therapy
Authors: Takayama Shin , Takashima Shigeru , Okajima Junnosuke , Watanabe Masashi , Kamiya Tetsuharu , Seki Takashi , Yamasaki Miyako , Yaegashi Nobuo , Yambe Tomoyuki , Maruyama Shigenao
Published: June 2012

Moxibustion therapy has been used in East Asian medicine for more than a thousand years. However, there are some problems associated with this therapy in clinical practice. These problems include lack of control over the treatment temperature, emission of smoke, and uneven temperature distribution over the treatment region. In order to resolve these problems, we developed a precise temperature-control device for use as an alternate for conventional moxibustion therapy. In this paper, we describe the treatment of a single patient with paralytic ileus that was treated with moxibustion. We also describe an evaluation of temperature distribution on the skin surface after moxibustion therapy, the development of a heat-transfer control device (HTCD), an evaluation of the HTCD, and the clinical effects of treatment using the HTCD. The HTCD we developed can heat the skin of the treatment region uniformly, and its effect may be equivalent to conventional moxibustion, without the emission of smoke and smell. This device can be used to treat ileus, abdominal pain, and coldness of abdomen in place of conventional moxibustion in modern hospitals.
Listeria monocytogenesin Ready-to-Eat Seafood and Potential Hazards for the Consumers
Authors: Gambarin Patrizia , Magnabosco Cristian , Losio Marina Nadia , Pavoni Enrico , Gattuso Antonietta , Arcangeli Giuseppe , Favretti Michela
Published: June 2012

The risk of exposure toListeria monocytogenes(L. monocytogenes) when consuming Ready-to-Eat (RTE) seafood was assessed in the Veneto Region (Italy). Thirty-eight samples were analyzed, each sample consisted of three subunits belonging to the same batches. The first of the three units was examined immediately, the second was stored at +4°C (for all of its shelf-life) and the third at +10°C (for the latter third of itsshelf-life) before the analysis. Chemical-physical and microbiological parameters were tested simultaneously. Culture results showed the presence of viableL. monocytogenesin 9 (23,68%) of the 38 samples analysed, 3 (33,33%) of which with a concentration >100 cfu/g. PCR tests yielded 12L. monocytogenespositive samples. Semipreserves with aw (water activity) and pH values that favourL. monocytogenesgrowth were the only ones to result positive to microbiological and PCR tests. Temperature proved to be an important factor as it limits the growth ofL. monocytogenes, including products with potentially high competitive microbial charges. Four different serotypes were recovered and ribotyping has helped to highlight the genomic variability ofL. monocytogenesstrains in food. This supports the hypothesis thatL. monocytogenescontinues to evolve genetically to the detriment of phenotypic conservation.
Induction of Fetal HemoglobinIn VivoMediated by a Syntheticγ-Globin Zinc Finger Activator
Authors: Costa Flávia C. , Fedosyuk Halyna , Neades Renee , de Los Rios Johana Bravo , Barbas Carlos F. , Peterson Kenneth R.
Published: June 2012

Sickle cell disease (SCD) andβ-thalassemia patients are phenotypically normal if they carry compensatory hereditary persistence of fetal hemoglobin (HPFH) mutations that result in increased levels of fetal hemoglobin (HbF,γ-globin chains) in adulthood. Thus, research has focused on manipulating the reactivation ofγ-globin gene expression during adult definitive erythropoiesis as the most promising therapy to treat these hemoglobinopathies. Artificial transcription factors (ATFs) are synthetic proteins designed to bind at a specific DNA sequence and modulate gene expression. The artificial zinc finger gg1-VP64 was designed to target the −117 region of theAγ-globin gene proximal promoter and activate expression of this gene. Previous studies demonstrated that HbF levels were increased in murine chemical inducer of dimerization (CID)-dependent bone marrow cells carrying a humanβ-globin locus yeast artificial chromosome (β-YAC) transgene and in CD34+erythroid progenitor cells from normal donors andβ-thalassemia patients. Herein, we report that gg1-VP64 increasedγ-globin gene expressionin vivo, in peripheral blood samples from gg1-VP64β-YAC double-transgenic (bigenic) mice. Our results demonstrate that ATFs function in an animal model to increase gene expression. Thus, this class of reagent may be an effective gene therapy for treatment of some inherited diseases.
Nd:YAG Lasers Treating of Carious Lesion and Root Canal In Vitro
Authors: Xia Danqing , Mo Zenggui , Zhao Gang , Guo Fei , You Chao , Chen Ze , Zhu Xiao , Li Zhengjia , Chen Di , Fan Xiaohong
Published: June 2012

Dental caries is a transmissible bacterial disease process, with cavities at the end, and caused by acids from bacterial metabolism. The essence of dental treatment is to clean and disinfect bacterial contamination from the tooth. In this work, we tried to demonstrate the cleaning and disinfecting effects of Nd:YAG laser irradiation on dental carious lesion and root canal in vitro. Acousto-optic Q-switched quasicontinuous and Cr3+:YAG crystal Q-switched pulse Nd:YAG lasers were employed to treat caries lesion and the root canal, respectively. Results showed that acousto-optic Q-switched quasicontinuous Nd:YAG laser irradiation and Cr3+:YAG crystal Q-switched pulse Nd:YAG laser irradiation could rapidly clean decayed material and bacterial contamination from dental carious lesion and the narrow tail end of root canal with minimally invasive in vitro, respectively. It was concluded that acousto-optic Q-switched quasicontinuous laser irradiation may be a rapid and effective alternative caries treatment, and Cr3+:YAG crystal Q-switched pulse Nd:YAG laser irradiation may be an effective method for canal cleaning and disinfecting during root canal therapy.
Native and Complexed IGF-1: Biodistribution and Pharmacokinetics in Infantile Neuronal Ceroid Lipofuscinosis
Authors: Huhtala Tuulia , Rytkönen Jussi , Jalanko Anu , Kaasalainen Martti , Salonen Jarno , Riikonen Raili , Närvänen Ale
Published: June 2012

Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder of childhood characterized by selective death of cortical neurons. Insulin-like growth factor 1 (IGF-1) is important in embryonic development and is considered as a potential therapeutic agent for several disorders of peripheral and central nervous systems. In circulation IGF-1 is mainly bound to its carrier protein IGFBP-3. As a therapeutic agent IGF-1 has shown to be more active as free than complexed form. However, this may cause side effects during the prolonged treatment. In addition to IGFBP-3 the bioavailability of IGF-1 can be modulated by using mesoporous silicon nanoparticles (NPs) which are optimal carriers for sustained release of unstable peptide hormones like IGF-1. In this study we compared biodistribution, pharmacokinetics, and bioavailability of radiolabeled free IGF-1, IGF-1/IGFBP-3, and IGF-1/NP complexes in a Cln1-/- knockout mouse model. IGF-1/NP was mainly accumulated in liver and spleen in all studied time points, whereas minor and more constant amounts were measured in other organs compared to free IGF-1 or IGF-1/IGFBP-3. Also concentration of IGF-1/NP in blood was relatively high and stable during studied time points suggesting continuous release of IGF-1 from the particles.
Stability and Limit Oscillations of a Control Event‐Based Sampling Criterion
Authors: De la Sen M. , Soto J. C. , Ibeas A.
Published: June 2012

This paper investigates the presence of limit oscillations in an adaptive sampling system. The basic sampling criterion operates in the sense that each next sampling occurs when the absolute difference of the signal amplitude with respect to its currently sampled signal equalizes a prescribed threshold amplitude. The sampling criterion is extended involving a prescribed set of amplitudes. The limit oscillations might be interpreted through the equivalence of the adaptive sampling and hold device with a nonlinear one consisting of a relay with multiple hysteresis whose parameterization is, in general, dependent on the initial conditions of the dynamic system. The performed study is performed on the time domain.
Developmental Potential for Endomorphin Opioidmimetic Drugs
Authors: Okada Yoshio , Tsuda Yuko , Salvadori Severo , Lazarus Lawrence H.
Published: June 2012

Morphine, which is agonist for μ-opioid receptors, has been used as an anti-pain drug for millennia. The opiate antagonists, naloxone and naltrexone, derived from morphine, were employed for drug addiction and alcohol abuse. However, these exogenous agonists and antagonists exhibit numerous and unacceptable side effects. Of the endogenous opioid peptides, endomorphin(EM)-1 and endomorphin(EM)-2 with their high μ-receptor affinity and exceptionally high selectivity relative to δ- and κ-receptors in vitro and in vivo provided a sufficiently sequence-flexible entity in order to prepare opioid-based drugs. We took advantage of this unique feature of the endomorphins by exchanging the N-terminal residue Tyr1 with 2′,6′-dimethyl-L-tyrosine (Dmt) to increase their stability and the spectrum of bioactivity. We systematically altered specific residues of [Dmt1]EM-1 and [Dmt1]EM-2 to produce various analogues. Of these analogues, [N-allyl-Dmt1]EM-1 (47) and [N-allyl-Dmt1]EM-2 (48) exhibited potent and selective antagonism to μ-receptors: they completely inhibited naloxone- and naltrexone-induced withdrawal from following acute morphine dependency in mice and reversed the alcohol-induced changes observed in sIPSC in hippocampal slices. Overall, we developed novel and efficacious opioid drugs without deleterious side effects that were able to resist enzymatic degradation and were readily transported intact through epithelial membranes in the gastrointestinal tract and the blood-brain-barrier.
More Than Flow: Revisiting the Theory of Four Channels of Flow
Authors: Teng Ching-I , Huang Han-Chung
Published: June 2012

Flow (FCF) theory has received considerable attention in recent decades. In addition to flow, FCF theory proposed three influential factors, that is, boredom, frustration, and apathy. While these factors have received relatively less attention than flow, Internet applications have grown exponentially, warranting a closer reexamination of the applicability of the FCF theory. Thus, this study tested the theory that high/low levels of skill and challenge lead to four channels of flow. The study sample included 253 online gamers who provided valid responses to an online survey. Analytical results support the FCF theory, although a few exceptions were noted. First, skill was insignificantly related to apathy, possibly because low-skill users can realize significant achievements to compensate for their apathy. Moreover, in contrast with the FCF theory, challenge was positively related to boredom, revealing that gamers become bored with difficult yet repetitive challenges. Two important findings suggest new directions for FCF theory.
Abstract A17: Prostate cancer screening of African American men aged 40–75 in Jefferson County, Arkansas
Authors: Rice Sederick , Taylor Felicia , William Torrence , Mosley Letha J. , Smith Michelle R. , Baldwin Helen
Published: June 2012

Prostate Cancer Screening of Men in Jefferson County, Arkansas applicably named Men Aware of Cancer (MAC) is an interdisciplinary pilot study that aims to utilize a Community Popular Opinion Leaders model (CPOL) by recruiting ten community leaders, who will recruit one-hundred (100) men of Black/African American) descent, aged 40–75, in Jefferson County, Arkansas, for a prostate cancer prevention awareness and action program. The MAC pilot program seeks to educate the community about co-morbidities and other health related issues such as obesity, dietary intake, and physical inactivity behaviors that play a role in the onset and development of prostate cancers. Ten CPOLs will be recruited through local churches, barbershops, civic organizations, and physician's offices, and trained to assist in reaching and mentoring the target population in Jefferson County, Arkansas. CPOLs will assist in the discussion and dissemination of literature, identification of patient barriers to active individual prevention and screening, and recruit participants for the educational components of the program that will be provided throughout the year. The MAC pilot program will also provide community based, accessible, and culturally relevant programming, that will bridge the gap between community members and health care. The overall goal is to affect the disproportionate cancer health disparities experienced in Black/African American communities in Jefferson County and throughout Arkansas.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A17.
Abstract A66: βarrestin2 contributes to aggressive tumor growth in African American prostate cancer cells
Authors: Thomas Ariel J. , Akins-Rivers Elizabeth J.
Published: June 2012

Prostate cancer (PCa) is the second leading cause of death in African American males (AA). Studies have found the incidence of PCa to be 60% higher in AA men than their Caucasian American counterparts (CA). Poorer prognosis in AA men is exacerbated by lack of adequate access to healthcare and non financial factors such as distrust of the healthcare system. However, these social and socioeconomic factors fail to fully account for this disparity. AA men are diagnosed at younger ages and often present with more advanced tumor stages and higher Gleason scores. Thus, elucidating possible biological causes of prostate cancer disparity is of utmost importance.

βarrestin2 (βarr2) is a scaffold protein that associates with G protein coupled receptors (GPCRs) and leads to the desensitization and internalization of these receptors. In addition, more recent studies have implicated βarr2 in a variety of cellular processes including androgen metabolism. We have shown increased βarrestin2 expression in prostate cell lines from AA men (MDA PCa 2B) when compared to those from CA men (LNCap). Furthermore, overexpression of βarr2 in LNCap cells or knockdown of βarr2 in MDA PCa 2B cells was sufficient to alter the growth properties of these cells. These results were seen both in vitro and in vivo. Thus preliminary data indicates that βarr2 may contribute to differences between tumor growth in our model system. Further studies are needed to ascertain the cause and mechanism of βarr2 overexpression in AA men, as well as the clinical significance of these findings.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A66.
Abstract A79: Socioeconomic status, health care density, and risk of prostate cancer among African-American men in a large prospective study
Authors: Major Jacqueline M. , Oliver M. Norman , Doubeni Chyke A. , Graubard Barry I. , Sinha Rashmi
Published: June 2012

Background: Given the large racial differences in prostate cancer risk, further investigation of socioeconomic (SES) indicators at the individual and community level is warranted among high-risk groups. The purpose of this study was to examine the association between neighborhood deprivation, healthcare facilities, and prostate cancer risk among African-American men.

Methods: In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995–1996) data from African-American participants, ages 50–71 years. Incident prostate cancer cases (n=1,089) were identified through December 2006. Life-style and health risk information was ascertained by questionnaires administered at baseline. Area-level socioeconomic indicators were ascertained by linkage to the US Census and the Area Resource File. Multilevel survival models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Among African-American men, no associations were observed between area-level factors and development of nonadvanced prostate cancer. Compared to African-American men living in counties with the highest density of radiologists, those in the middle tertile had the highest risks of advanced prostate cancer (HR=2.88, 95% CI=1.61-5.18), however, no significant trend was found (Ptrend=0.08).

Certain socioeconomic (SES) indicators were positively associated with prostate cancer risk among African-American men. Further studies are needed to replicate these findings.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A79.
Abstract A82: Understanding disparities in acute leukemia: A national study
Authors: Patel Manali I. , Ma Yifei , Mitchell Beverly , Rhoads Kim
Published: June 2012

Background: Disparities in solid tumors have been well studied. However disparities in hematologic malignancies in adults remain relatively unexplored. The purpose of this study is to explore the relationship between race/ethnicity and mortality from acute leukemia among adults.

Methods: All patients with acute leukemia (Acute Lymphoblastic Leukemia (ALL) and Acute Myelogenous Leukemia (AML)) were identified in the Surveillance Epidemiology and End Results (SEER) database, 1998–2008. Kaplan Meier curves were generated to reflect mortality by race/ethnicity. Multivariable Cox proportional hazard models estimated hazard of mortality by race with adjustment for individual covariates (age, gender) and specific chromosomal translocations (11q23 and 15;17q24;q21).

Results: A total of 40,951 patients with acute leukemia were included in the study. Overall, there was a disparity in mortality in acute leukemia for Blacks (HR 1.17, p<0.0001) and Hispanics (HR 1.12, p<0.0001) compared with Non-Hispanic Whites (NHW). In stratified analysis, disparities in ALL were greater than AML; Blacks (HR[ALL]1.45 p<.0001; HR[AML]1.12 p<0.0001); Hispanics (HR[ALL]1.46 p<0.0001; HR[AML]1.06 p<0.01). Adjustment for individual patient factors and chromosomal translocations do not explain the disparities in ALL or AML. There was no disparity among Asian/Pacific Islander populations compared with NHW.

Conclusions: Overall, disparities in acute leukemia mortality exist for Blacks and Hispanics compared with NHWs. While incidence and mortality are consistently increased among Hispanics with acute leukemia, Blacks suffer from a low incidence but higher mortality paradox as is seen in other solid tumors such as breast cancer. Further investigation is needed to understand the drivers of poor outcomes in these populations.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A82.
Abstract A89: Examination of ancestral informative markers and self-reported race with tumor characteristics of breast cancer among black and white women
Authors: Reding Kerryn W. , Carlson Christopher S. , Malone Kathleen E. , Chen Christina T. , Doody David R. , Ornelas India , Chen Chu , Lowe Kimberly , Weiss Linda , Simon Michael , Strom Brian
Published: June 2012

African American (AA) women have higher mortality from breast cancer (BC) compared to European American (EA) women. This may be due to the higher proportion of AA women with tumors that are diagnosed at advanced stage and are estrogen receptor negative (ER-) /progesterone receptor negative (PR-). Our study sought to determine whether self-reported race and percent African ancestry were associated with BC tumor characteristics. In a multi-center, population-based case-control study of BC, we determined percent African ancestry using ancestry informative markers (AIM) among women self-reporting as Black. While self-reported race was associated with several BC tumor characteristics, AIMs markers among AA women were not. Specifically, women self-reporting as Black were at a 30% reduction in ER+/PR+ tumors (95% CI: 0.6–0.9), a non-significant risk of ER-/PR-tumors (OR = 1.3 [95% CI: 0.9–1.7]), a 1.4-fold increased risk of regional/distant stage (95% CI: 1.1–1.7) and a 1.5-fold increased risk of high grade tumors (95% CI: 1.2–1.9) compared to EA women. Percent African ancestry was not associated with any BC tumor characteristics (OR=1.0 for ER+/PR+ [95% CI: 0.6–1.8], OR = 0.9 for ER-/PR-[95% CI: 0.5–1.6], OR = 1.3 for regional/distant stage [95% CI: 0.8–2.1], and OR=0.9 for high-grade tumors [95% CI: 0.6–1.4] comparing those with ≥95% African ancestry to those with <80% African ancestry). This analysis suggests that factors unrelated to AA women's genetic ancestry contribute to racial differences in BC tumor characteristics.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A89.
Abstract B31: Molecular signature discriminating triple-negative breast tumors between African American and Caucasian women
Authors: Ellsworth Rachel , Field Lori , Shriver Craig
Published: June 2012

Background: Triple negative (TN) tumors are characterized by aggressive behavior and, the negative hormone receptor and HER2 status precludes the use of personalized therapies such as tamoxifen and trastuzumab. African American women have higher rates of both breast cancer mortality as well as TN breast tumors. What remains unknown is how much of these disparities can be attributed to molecular differences between populations.

Methods: The Clinical Breast Care Project database was queried to identify African American women with triple negative, high-grade tumors. Caucasian women with highgrade TN tumors were then matched by age at diagnosis, tumor stage, size and lymph node status. RNA was isolated after laser microdissection of the tumor and hybridized to HG U133A 2.0 microarrays. Data was analyzed using Partek Genomics Suite.

Results: Principal Component Analysis accurately clustered the triple negative specimens by ethnicity. Using a false-discovery rate (FDR) p-value <0.05 with a minimum 2.0-fold change of expression, 132 probes from 117 genes were differentially expressed. Hierarchical clustering using a subset of these probes (P<0.00001) representing 23 known genes reliably partitioned all samples as African American or Caucasian. Genes differentially expressed include lower expression of AQP5, VEGF and RAD51C and higher expression of hemoglobin B, and complement factors CFD and C4A in tumors from African Americans.

Discussion: Despite matching of tumors by clinicopathological characteristics, molecular profiles of triple negative breast tumors differed between AAW and CW. These differences may serve as molecular targets for the development of novel prevention strategies and therapeutics to reduce the risk of developing and improve treatment of African American women with triple negative breast cancer.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B31.
Abstract B64: Low estrogen receptor expression level and early age of breast cancer onset are the common breast cancer features in Arab population
Authors: Dhaheri Mariam Al
Published: June 2012

Breast cancer is the common malignant related disease of Women worldwide. In clinic, molecular classification of the disease is a key to setup therapeutic strategy for patients. To date, few reports describe the molecular basis of the disease, survival rate and therapeutic strategies that applied to encounter breast cancer in the Arab population. Nevertheless, advancement of medical research varied among Arab nations. This study reviews published data of breast cancer in the Arab World and integrate the available data to propose a model that describes the common molecular features of breast cancer in the Arab population. In conclusion, almost all of Arab nations share an early onset of breast cancer. Grade I cases accounted for ≤10% of the total cases, while grade III cases accounted for ≥40% of the total diagnosed cases. In general, breast tumor poor differentiation is associated with decrease in estrogen receptor (ER) and B-cell lymphoma 2 (Bcl2) expression and an increase of protein 53 (p53) protein expression. Human epidermal growth factor receptor 2 (HER2/neu) expression is varied, yet it is associated with poor differentiation. Most importantly ER expression level is relatively lower compared to the reported ER expression level in breast cancer cases detected in Western countries. This could be due to the fact that the majority of breast cancer cases detected in Arab population were grade II or III of cancer progression. The dominance of advanced form of the disease with early age of onset urge to screen samples to identify biomarkers associated with breast cancer onset in Arab population. In deed; identifying new biomarkers responsible of early onset of the disease might advance our understanding of disease progression and/ or discover new molecular therapeutic targets.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B64.
Abstract B75: Association of insurance status and age with stage at diagnosis among cervical cancer patients, National Cancer Database 2000–2007
Authors: Fedewa Stacey A. , Virgo Katherine S. , Bandi Priti , Saslow Debbie , Ward Elizabeth M. , Cokkinides Vilma
Published: June 2012

Introduction: Late stage cervical cancer at diagnosis is associated with greater morbidity and mortality and higher treatment costs. Few studies have examined the association between insurance status and cervical cancer stage at diagnosis. Existing studies have been either state-specific or limited to elderly Medicare recipients. This study aims to examine the relationship between patient characteristics, with a particular focus on age at diagnosis and insurance status, and stage in a large number of cervical cancer patients aged 21–85 in the National Cancer Database (NCDB).

Methods: Women diagnosed with their first primary invasive cervical cancer between 2000 and 2007 were selected from the NCDB. We evaluated the association between late stage (stage III/IV) and insurance and age while adjusting for race/ethnicity and other socio-demographic and clinical factors. Multivariate log binomial models were used to estimate risk ratios (RR) and 95% confidence intervals (CIs), respectively.

Results: Among the 69,739 evaluable patients, the rate of late stage disease increased from 16.53% in 21–34 year olds to 42.44% in women ≥70. The adjusted risk of advanced stage of disease among women 50 years and older was 2.2 to 2.5 times that of patients aged 21–34. Uninsured (RR=1.44, 95% CI 1.40–1.49), Medicaid (RR=1.37, 95% CI 1.34–1.41), Younger Medicare (RR=1.12, 95% CI 1.06–1.19), and Older Medicare (RR=1.20, 95% CI 1.15–1.26) patients had a higher risk of late stage disease compared to privately insured patients. African Americans (RR=1.05, 95%CI 1.02–1.08) had slightly higher risks of advanced stage disease while Hispanics (RR=0.86, 95%CI 0.83–0.89) and other race/ethnicities (RR=0.88, 95%CI 0.84–0.92) had a lower risks compared to whites.

Conclusion: In a large national sample of women diagnosed with cervical cancer, the strongest predictor of late stage at diagnosis was age. Patients without private insurance were also more likely to be diagnosed at later stages, particularly uninsured and Medicaid insured patients. Screening should be encouraged for those women for whom it is recommended, especially those at higher risk of advanced stage disease. Consideration of these findings in developing future guidelines for cervical cancer screening among older women is recommended.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B75.
Abstract B83: Factors influencing adherence to mammography screening guidelines in Appalachian women participating in a mobile mammography program
Authors: Vyas Ami , Madhavan S. Suresh , Lemasters Traci , Atkins Elvonna , Kennedy Stephenie , Kelly Kimberly , Vona-Davis Linda , Halverson Joel , Remick Scot
Published: June 2012

Objectives: The objectives of this study were to evaluate the characteristics (demographic, access to care, health-related behavioral, self and family medical history, psychosocial) of women age 40 years and above who participated in a mobile mammography screening program conducted throughout West Virginia to determine the factors influencing their self-reported adherence to mammography screening guidelines.

Methods: The data were collected from 738 women who participated in the Bonnie Wells Wilson Mobile Mammography Program and completed a six-page Preventive Care Survey. Data were analyzed using the Andersen Behavioral Model of Healthcare Utilization framework to determine the factors associated with adherence to mammography screening guidelines in these women.

Results: Of the 686 women included in the analysis, 46.2% reported having had a mammogram in the past two years as per current mammography screening guidelines. The unadjusted model showed predisposing factors such as older age and unemployed status, visit to a gynecologist in the past year (an enabling factor) and need-related factors such as having a family history of breast cancer (BC), having had breast problems in the past, having had breast biopsy in the past, having had a Pap test in past two years, and having had all the screenings for cholesterol, blood glucose, bone mineral density and high blood pressure in past two years to be significant predictors of self-reported adherence to mammography guidelines. In the adjusted model, being of age 65 and above (OR=3.787), having a family history of BC (OR=1.909), having had breast problems in the past (OR=1.992) and having had a Pap test (OR=6.035) were significant predictors of self-reported mammography screening adherence.

Conclusions: Forty-six percent of the sample reported having had a mammogram in the past two years as per current mammography screening guidelines which is lower than the 70% goal of Healthy People 2010. Breast cancer related events seem to be associated with mammography screening adherence in this rural Appalachian population. Increasing adherence to mammography screening may require targeted, community-based educational interventions that precede and complement visits by the mobile mammography unit.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B83.
Abstract ED03-01: Validation and quantitation of DNA methylation changes
Authors: Kwabi-Addo Bernard
Published: June 2012

Advances in the molecular mechanisms underlying prostate cancer demonstrates that prostate cancer cells carry a myriad of genomic defects including both genetic and epigenetic alterations such as DNA methylation. Underlying this aberrant DNA methylation is the accumulating body of data hinting that normal prostate cells may be subjected to a relentless barrage of genome-damaging stresses due to both exogenous and endogenous carcinogens, with damage accumulating over time and age. There are increasing numbers of genes that show aberrant DNA methylation changes in human prostate cancer. In addition, recent reports indicate widespread methylation changes that correlate with a broad range of clinical behavior in prostate cancer patients. Thus aberrant DNA methylation changes may represent the integration of environmental or lifestyle exposures and genetic predisposition to prostate cancer. Such events may differ between individuals belonging the same ethnic group or individuals belonging to different ethnic groups. We hypothesize that differential methylation patterns maybe associated with ethnicity and could potentially contribute to the incidence and mortality of prostate cancer. Our research studies validate and quantify selected regions of genes from a genome-wide methylation analysis in a large sample number from African American and Caucasian male patients with prostate cancer. Our preferred method for studying DNA methylation is pyrosequencing over other methods of methylation analysis in that it is processive and quantitative. The principle of pyrosequencing is the real-time detection of pyro-phosphate (PPi), released after each incorporation of a specific nucleotide, initiated by simple primer extension on a PCR product template. Pyrosequencing has both qualitative and quantitative applications, and is optimal for allele quantification, DNA methylation estimation, and for regions that contain multiple polymorphisms (SNPs, IN/DELs) adjacent or in close proximity. Using this approach, we have observed significant differences in the methylation pattern for several genes in prostate tissue samples from African American and Caucasian men. Such alterations can contribute to the biological differences underlying prostate cancer disparity.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):ED03-01.
Abstract PL04-02: Efficacy of PSA screening for prostate cancer: A case-control study of Caucasian and African American Medicare beneficiaries
Authors: Godley Paul A. , Carpenter William R. , Edwards Lloyd J. , Talcott James A. , Zullig Leah L. , Peacock Sharon , Schenck Anna P.
Published: June 2012

Background: PSA screening has become standard practice in the US although mortality data from controlled trials is lacking to assess the efficacy of screening of African American men. We investigated whether PSA screening efficacy is similar among elderly Caucasian and African American men.

Methods: This case-control study compared PSA exposure history of Surveillance, Epidemiology, and End Results (SEER) dataset-derived cases deceased from prostate cancer to that of control subjects from a linked Medicare dataset. The prostate cancer cases include males diagnosed with prostate cancer between 1992 and 2005 that subsequently died from the disease (matched with 3:1 on race, age, and SEER region).

Results: We identified 8,846 cases deceased from prostate cancer, and 23,538 age-, race-, and SEER site-matched controls. African Americans comprised about 10% of both the cases (779) and controls (2,337). Conditional logistic regression analyses were used to calculate prostate cancer-specific mortality among African American (1.09 [95% CI 0.917–1.303]) and Caucasian subjects (1.14 [95% CI 1.076–1.201]) who were asymptomatic at the time of their PSA screening test.

Conclusions: The results of this large, claims-based, case-control study suggest that the efficacy of PSA screening among elderly African American men is not dissimilar to that of elderly Caucasian men, and that neither group benefitted from reduced mortality attributable to screening.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):PL04-02.