bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the hydrodynamic forces on geobag revetments
Authors: Akter A. , Pender G. , Wright G. , Crapper M.
Published: August 2011

Sand‐filled geotextile bags (geobags) are commonly used for riverbank protection, however, despite their deployment in a significant number of locations, the failure modes of such structures are not well understood. This paper describes a series of 1:10 physical model tests designed to improve our understanding of the basic failure modes of geobag revetments used as river bank protection. In particular, the aim of the experimental programme is to quantify the relationship between hydraulic shear stress on the revetment surface and geobag displacement. The aspect of the work reported is the use of two analytical techniques, the Conveyance Estimation System (CES) and the membrane analogy method developed by Chow to predict hydraulic shear stress on the geobag surface. It is concluded that both methods produce acceptable shear stress predictions for the initially washed away bags, although the CES is recommended for future use because of its better prediction and ease of application.
COI is better than 16S rRNA for DNA barcoding Asiatic salamanders (Amphibia: Caudata: Hynobiidae)
Authors: XIA YUN , GU HAI‐FENG , PENG RUI , CHEN QIN , ZHENG YU‐CHI , MURPHY ROBERT W. , ZENG XIAO‐MAO
Published: August 2011

The 5′ region of the mitochondrial DNA (mtDNA) gene cytochrome c oxidase I (COI) is the standard marker for DNA barcoding. However, because COI tends to be highly variable in amphibians, sequencing is often challenging. Consequently, another mtDNA gene, 16S rRNA gene, is often advocated for amphibian barcoding. Herein, we directly compare the usefulness of COI and 16S in discriminating species of hynobiid salamanders using 130 individuals. Species identification and classification of these animals, which are endemic to Asia, are often based on morphology only. Analysis of Kimura 2‐parameter genetic distances (K2P) documents the mean intraspecific variation for COI and 16S rRNA genes to be 1.4% and 0.3%, respectively. Whereas COI can always identify species, sometimes 16S cannot. Intra‐ and interspecific genetic divergences occasionally overlap in both markers, thus reducing the value of a barcoding gap to identify genera. Regardless, COI is the better DNA barcoding marker for hynobiids. In addition to the comparison of two potential markers, high levels of intraspecific divergence in COI (>5%) suggest that both Onychodactylus fischeri and Salamandrella keyserlingii might be composites of cryptic species.
Melanotic neuroectodermal tumor of infancy: a histopathological and immunohistochemical study
Authors: Mendis Balapuwaduge Ranjit Rigobert Nihal , Lombardi Tommaso , Tilakaratne Wanninayake Mudiyanselage
Published: August 2011

Melanotic neuroectodermal tumor of infancy is an uncommon neoplasm that normally occurs in the anterior maxilla of children less than 1 year of age. This is a tumor with controversial origin, although neural crest origin is proposed. This case report presents an analysis of histopathological and immunohistochemical findings in this rare tumor.
Why Impacted Yarns Break at Lower Speed Than Classical Theory Predicts
Authors: Walker James D. , Chocron Sidney
Published: August 2011

Fabrics are an extremely important element of body armors and other armors. Understanding fabrics requires understanding how yarns deform. Classical theory has shown very good agreement with the deformation of a single yarn when impacted transversely. However, the impact speed at which a yarn breaks based on this classical theory is not correct; it has been experimentally noted that yarns break when impacted at a lower speed. This paper explores the mechanism of yarn breakage. The problem of the transverse strike of a yarn by a flat-faced projectile is analytically solved for early times. It is rigorously demonstrated that when a flat-faced projectile strikes a yarn, the minimum impact speed that breaks the yarn will always be at least 11% less than the classical-theory result. It is further shown that when the yarn in front of the projectile “bounces” off the projectile face due to the impact, the impact speed that breaks the yarn is further reduced. If the yarn bounces elastically off the projectile face at twice the impact velocity (the theoretical maximum), there is a 40% reduction in the projectile impact speed that breaks the yarn.
Development of a Colonoscope Sheath Device for Colonoscopy
Authors: Choi JungHun , Drozek David
Published: August 2011

Endoscopy is a minimally invasive procedure using instruments that pass through the body for diagnostic purposes and minimizes the risks associated with open surgery. Colonoscopy can viewed as an endoscopic procedure of the colon. Colonoscopy may cause extreme discomfort to the patient and also carries the risks of perforating the lining of the colon, splenic ruptures, or bleeding. The technology is an endoscope that has an exoskeleton structure of controllable stiffness and a highly flexible stem. The device saves the patient from the pain caused by the shaft of a colonoscope when it is guided from the anus to the end of the sigmoid colon. The stiffenable sheath guides the shaft of the colonoscope up to the end of the sigmoid colon to avoid looping the shaft of the colonoscope. A prototype of the device was built and tested to validate its effectiveness. In order to further improve the performance of the device, skilled endoscopists tested and validated the device using a colonoscopy training model. The colonoscopy training model is comprised of a configurable rubber colon, a human torso, a display, and sensing part. It measures the forces caused by the distal tip and the shaft of the colonoscope and the pressure to open up the lumen. The force sensors at the rubber colon constraints measure the forces, and the real-time display panel will show the results to the colonoscopist and record the data for analysis. The endoscopy sheath device improves the process of endoscopy by reducing the mechanical trauma and loops caused by the shaft of the endoscope. With the guide provided by the colonoscope sheath, the forces to the constraints of a colon are significantly decreased in the sigmoid colon. The colonoscope sheath helps to reduce the force to constraints of the colon and isolates the direct contact between the shaft of a colonoscope and a colon wall up to the end of the sigmoid colon. For the complicated shape of the colon, the endoscopy sheath also solved possible looping problems. The colonoscope training model effectively measures the forces and makes it possible to validate the effectiveness of the endoscopy sheath.
Ovulation induction with clomifene: a primary care perspective
Authors: Wilkes Scott , Murdoch Alison
Published: August 2011

Infertility affects one in seven couples during their lifetime. Approximately one-quarter of these will have an ovulatory disorder contributing to their inability to conceive. Ovulatory disorders represent the simplest form of infertility to treat, and where this is not a result of ovarian failure or poor ovarian reserve most women require ovulation induction with clomifene citrate (CC). This review aims to examine the role of CC in a general practice setting. CC is a simple, relatively safe, easily administered and well-tolerated efficacious drug. There is, however, a 10% risk of multiple births associated with its use. CC has been used in general practice for many years and continues to be used. Currently, guidelines do not describe its use in the general practice setting and the evidence for monitoring its use with mid-luteal progesterone estimation or ultrasound scanning is conflicting.
A PAS domain within F plasmid TraJ is critical for its function as a transcriptional activator
Authors: Arutyunov D. , Rodriguez-Maillard J.M. , Frost L.S.
Published: August 2011

TraJ is the positive activator of the major transfer operon in the F plasmid of Escherichia coli that counteracts H-NS silencing at the main transfer promoter (PY). Multiple sequence alignment revealed a putative PAS (Per-ARNT-Sim) domain that might be involved in sensing redox potential or energy levels in the cell. This domain, which contains a conserved PXCXR motif along with a C(X)9–10CR/N/K motif of variable position, was identified within the N-terminal region of TraJ orthologues including F TraJ. The 5 cysteine residues in F TraJ were changed to serine to give protein with single or multiple substitutions. Single C to S substitutions had little effect on mating efficiency (ME), whereas cumulative substitutions from the N- to the C-termini (2CS to 5CS) gradually reduced ME to undetectable levels. F TraJ was able to bind to Fe (III) on an affinity sorbent column. This feature was severely impaired for the 5CS mutant. Thus, the cysteine residues within the PAS domain could be the part of a metal-containing redox centre that plays a key role in the transcriptional activation of the PYoperon by TraJ.
OxLDL-mediated survival of macrophages does not require LDL internalization or signalling by major pattern recognition receptors
Authors: Riazy Maziar , Chen Johnny H. , Yamamato Yasuhiko , Yamamato Hiroshi , Duronio Vincent , Steinbrecher Urs P.
Published: August 2011

Macrophages play a key role in the pathogenesis of atherosclerosis, in part by destabilizing plaques. We and others have shown that low concentrations of oxidized LDL (oxLDL) inhibit macrophage apoptosis. As oxLDL is present in lesions, this may be a mechanism by which macrophage populations in the intima are expanded. We have previously shown that oxLDL activates prosurvival signalling pathways such as the phosphoinositide 3-kinase (PI3K) pathway in bone marrow derived macrophages (BMDMs). However, little is known about more upstream signalling events especially at the receptor level. The endocytic pattern recognition receptors (PRRs), scavenger receptor A (SR-A) and CD36, are the main receptors on macrophages for uptake of oxLDL and are therefore important in foam cell formation. The signalling PRRs such as toll-like receptor (TLR) 2 and 4 also bind some types of oxLDL. This study was done to determine if any of the known PRRs are required for the anti-apoptotic effects of oxLDL in BMDMs. To do this, we tested the effect of oxLDL on viability of BMDMs lacking both SR-A and CD36 or lacking TLR2, TLR4, CD14, FcγRIIb, or RAGE. Our results indicate that none of these receptors are essential for activating the oxLDL prosurvival pathway. Furthermore, we show that the anti-apoptotic effect is not dependent on the uptake of oxLDL.
Recent success in the discovery of coronary artery disease genes
Authors: Roberts Robert , Chen Li , Wells George A. , Stewart Alexandre F.R.
Published: August 2011

For more than 50 years, epidemiological studies have indicated that genetic predisposition accounts for approximately 50% of the susceptibility to coronary artery disease (CAD) and its sequelae, including myocardial infarction. Since common diseases such as CAD are caused by multiple genes, the age-old method of linkage analysis used to map monogenic Mendelian disorders in families unfortunately lacks the required sensitivity. The technology to identify genes predisposing individuals to CAD and other common diseases did not become available until 2005. This technology provided computerized arrays containing hundreds of thousands of DNA markers in the form of single-nucleotide polymorphisms (SNPs). This made it possible to pursue an unbiased approach referred to as genome-wide association studies. The first gene for CAD was simultaneously identified by 2 independent groups in 2007. In a very short interval, a total of 23 loci were mapped that were linked to increased risk for CAD. The results of these studies confirm that CAD is caused by multiple genes, each contributing minimal risk. The most exciting and novel findings are that these loci do not act through known risk factors for CAD and that the loci are more likely to be in DNA regions that regulate transcription rather than being in coding regions for protein.
M-CAT element mediates mechanical stretch-activated transcription of B-type natriuretic peptide via ERK activation
Authors: Koivisto Elina , Karkkola Laura , Majalahti Theresa , Aro Jani , Tokola Heikki , Kerkelä Risto , Ruskoaho Heikki
Published: August 2011

The muscle-CAT (M-CAT) promoter element is found on promoters of most muscle-specific cardiac genes, but its role in cardiac pathology is poorly understood. Here we studied whether the M-CAT element is involved in hypertrophic process activated by mechanical stretch, and identified the intracellular pathways mediating the response. When an in vitro stretch model of cultured neonatal rat cardiomyocytes and luciferase reporter construct driven by rat B-type natriuretic peptide (BNP) promoter were used, mutation of M-CAT element inhibited not only the basal reporter activity (88%), but also the stretch-activated BNP transcription (58%, p < 0.001). Stretch-induced BNP promoter activation was associated with an increase in transcriptional enhancer factor-1 (TEF-1) binding activity after 24 h mechanical stretch (p < 0.05). Inhibition of mitogen-activated protein kinases ERK, JNK, or p38 attenuated stretch-induced BNP activation. Interestingly, as opposed to p38 and JNK, inhibition of ERK had no additional effect on transcriptional activity of BNP promoter harboring the M-CAT mutation, suggesting a pivotal role for ERK in regulating stretch-induced BNP transcription via M-CAT binding site. Finally, immunoprecipitation studies showed that mechanical stretch induced myocyte enhancer factor-2 (MEF-2) binding to TEF-1. These data suggest a central role for M-CAT element in regulation of mechanical stretch-induced hypertrophic response via ERK activation.
Atrial natriuretic factor in the developing heart: a signpost for cardiac morphogenesis
Authors: Bruneau Benoit G.
Published: August 2011

The developing heart forms during the early stages of embryogenesis, and misregulated heart development results in congenital heart defects (CHDs). To understand the molecular basis of CHDs, a deep understanding of the morphological and genetic basis of heart development is necessary. Atrial Natriuretic Factor (ANF) is an important and extremely sensitive marker for specific regions of the developing heart, as well as for disturbances in the patterning of the heart. This review summarizes the dynamic expression of ANF in the developing heart and its usefulness in understanding the early molecular defects underlying CHDs.
DRIVERS OF STABILITY OF CLIMATE COALITIONS IN THE STACO MODEL
Authors: DELLINK ROB
Published: August 2011

This paper investigates which drivers affect the formation and stability of international climate agreements (ICAs). The applied model STACO is used to project costs and benefits of an international agreement on climate change mitigation activities. The simulation results show that an incentive-based permit allocation scheme is an essential driver in stabilizing larger coalitions. Regional damage shares turn out to be another driver of coalition formation but global damages do not seem to be, thus illustrating that international coalition formation is a matter of relative costs and benefits across regions. No allocation scheme can, however, assure the stability of a global agreement due to huge free-rider incentives. This requires alternative rules, such as a condition that some players are essential in a coalition, or accepting a small loss from cooperation.
ADAPTATION AND CLIMATE CHANGE IMPACTS: A STRUCTURAL RICARDIAN MODEL OF IRRIGATION AND FARM INCOME IN AFRICA
Authors: KURUKULASURIYA PRADEEP , KALA NAMRATA , MENDELSOHN ROBERT
Published: August 2011

Although there is now an extensive literature on the economic impacts of climate change on agriculture, no study has yet addressed the endogeneity of irrigation. This paper examines how climate affects the choice to irrigate and the conditional income earned by each farmer. The paper develops a selection model of irrigation choice and conditional income. Using data from farmers across eleven African countries, the paper demonstrates that the choice of irrigation is sensitive to both temperature and precipitation. Rainfed and irrigated farm income also both respond to climate but have different climate sensitivity. Impact models that fail to account for endogenous irrigation are biased.
Fluid Retention over the Menstrual Cycle: 1-Year Data from the Prospective Ovulation Cohort
Authors: White Colin P. , Hitchcock Christine L. , Vigna Yvette M. , Prior Jerilynn C.
Published: August 2011

We report menstrual and mid-cycle patterns of self-reported “fluid retention” in 765 menstrual cycles in 62 healthy women. Self-reported “fluid retention,” commonly described as bloating, is one element of the clinical assessment and diagnosis of premenstrual symptoms. These daily diary data were collected as part of an observational prospective one-year study of bone changes in healthy women of differing exercise characteristics. Ovulation was documented by quantitative basal temperature analysis, and serum estradiol and progesterone levels were available from initial and final cycles. Fluid retention scores (on a 0–4 scale) peaked on the first day of menstrual flow (mean ± SE :0.9±0.1), were lowest during the mid-follicular period, and gradually increased from0.22±0.05to0.50±0.09over the 11 days surrounding ovulation. Mid-cycle, but not premenstrual, fluid scores tended to be lower in anovulatory cycles (ANOVAP=0.065), and scores were higher around menstruation than at midcycle (P<0.0001). Neither estradiol nor progesterone levels were significantly associated with fluid retention scores. The peak day of average fluid retention was the first day of flow. There were no significant differences in women's self-perceived fluid retention between ovulatory and anovulatory cycles.
Prevalence of Depression and Dementia among Adults with Developmental Disabilities in Manitoba, Canada
Authors: Shooshtari Shahin , Martens Patricia Joan , Burchill Charles A. , Dik Natalia , Naghipur Saba
Published: August 2011

Study Objective. To estimate and compare the prevalence of dementia and depression among adults with and without developmental disabilities (DDs). Methods. We linked data from several provincial administrative databases to identify persons with DDs. We matched cases with DD with persons without DD as to sex, age, and place of residence. We estimated the prevalence of dementia and depression and compared the two groups using the Generalized Estimating Equations (GEEs) technique. Results. The estimated prevalence of depression and dementia among younger adults (20–54) and older adults (50+) with DD was significantly higher than the estimated rates for the matched non-DD group (Depression: younger adults: RR = 2.96 (95% CI 2.59–3.39); older adults: RR = 2.65 (95% CI 1.84–3.81)), (Dementia: younger adults: RR = 4.01 (95% CI 2.72–5.92); older adults: RR = 4.80 (95% CI 2.48–9.31)). Conclusion. Significant disparities exist in mental health between persons with and without DDs.
Clinical Considerations ofBRCA1- andBRCA2-Mutation Carriers: A Review
Authors: Bougie O. , Weberpals J. I.
Published: August 2011

Individuals who carry an inherited mutation in the breast cancer 1 (BRCA1) andBRCA2genes have a significant risk of developing breast and ovarian cancer over the course of their lifetime. As a result, there are important considerations for the clinician in the counseling, followup and management of mutation carriers. This review outlines salient aspects in the approach to patients at high risk of developing breast and ovarian cancer, including criteria for genetic testing, screening guidelines, surgical prophylaxis, and chemoprevention.
Multiple Myeloma: A Review of Imaging Features and Radiological Techniques
Authors: Healy C. F. , Murray J. G. , Eustace S. J. , Madewell J. , O'Gorman P. J. , O'Sullivan P.
Published: August 2011

The recently updated Durie/Salmon PLUS staging system published in 2006 highlights the many advances that have been made in the imaging of multiple myeloma, a common malignancy of plasma cells. In this article, we shall focus primarily on the more sensitive and specific whole-body imaging techniques, including whole-body computed tomography, whole-body magnetic resonance imaging, and positron emission computed tomography. We shall also discuss new and emerging imaging techniques and future developments in the radiological assessment of multiple myeloma.
Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Depression
Authors: Salgado-Delgado Roberto , Tapia Osorio Araceli , Saderi Nadia , Escobar Carolina
Published: August 2011

Circadian factors might play a crucial role in the etiology of depression. It has been demonstrated that the disruption of circadian rhythms by lighting conditions and lifestyle predisposes individuals to a wide range of mood disorders, including impulsivity, mania and depression. Also, associated with depression, there is the impairment of circadian rhythmicity of behavioral, endocrine, and metabolic functions. Inspite of this close relationship between both processes, the complex relationship between the biological clock and the incidence of depressive symptoms is far from being understood. The efficiency and the timing of treatments based on chronotherapy (e.g., light treatment, sleep deprivation, and scheduled medication) indicate that the circadian system is an essential target in the therapy of depression. The aim of the present review is to analyze the biological and clinical data that link depression with the disruption of circadian rhythms, emphasizing the contribution of circadian desynchrony. Therefore, we examine the conditions that may lead to circadian disruption of physiology and behavior as described in depressive states, and, according to this approach, we discuss therapeutic strategies aimed at treating the circadian system and depression.
von Willebrand Factor and Oxidative Stress Parameters in Acute Coronary Syndromes
Authors: Koprivica Zoran , Djordjevic Dusica , Vuletic Milena , Zivkovic Vladimir , Barudzic Nevena , Andjelkovic Nebojsa , Djuric Dragan , Iric-Cupic Violeta , Krkeljic Jelena , Jakovljevic Vladimir
Published: August 2011

Considering the role of von Willebrand factor (vWf) in hemostasis, and the role of oxidative stress in the development of endothelial dysfunction and atherosclerotic disease, the aim of our study was to investigate the relationship between vWf, parameters of oxidative stress and different types of acute coronary syndromes (ACS). Levels of vWf activity (vWfAct), vWf antigen (vWfAg), nitric oxide (estimated through nitrites–NO2 −), superoxide anion radical (O2 −), hydrogen peroxide (H2O2), index of lipid peroxidation (estimated through thiobarbituric acid reactive substances–TBARS), superoxide dismutase (SOD) and catalase (CAT) activity of 115 patients were compared with those of 40 healthy controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well as TBARS levels, while their levels of NO2 −, H2O2, SOD and CAT activities were lower than controls'. vWfAg showed high specificity and sensitivity as a test to reveal healthy or diseased subjects. Multivariant logistic regression marked only vWfAg and TBARS as parameters that were under independent effect of ACS type. The results of our study support the implementation of vWf in clinical rutine and into therapeutic targets, and suggest that ACS patients are in need of antioxidant supplementation to improve their impaired antioxidant defence.
Thermally Stimulated Depolarization Current from HCl-Doped Ice
Authors: Choi Yoon Young
Published: August 2011

Thermally stimulated depolarization current (TSDC) technique has been applied to investigate the dielectric properties of the HCl-doped ice. Three TSDC peaks were found from HCl-doped ice as well as ice of pure water. Among three peaks, the α and γ peaks are affected strongly by the concentrations of HCl. We found that the pH numbers are linearly proportioned to the ratios of the areas of the peaks. The relation between xα (the ratio of the area of α peak to the area of β peak) and pHHCl,α was found to be pHHCl,α=7.77−2.86xα. This result suggests the possibility of the development of an apparatus to measure the pH number of acid contaminated water. The activation energies correspond to depolarization processes reflected in the α, β, and γ peaks that were found to be 267±19 meV, 431±30 meV, and 635±44 meV, respectively.
Substitution of Carbazole Modified Fluorenes as π-Extension in Ru(II) Complex-Influence on Performance of Dye-Sensitized Solar Cells
Authors: Chandrasekharam Malapaka , Rajkumar Ganugula , Suresh Thogoti , Rao Chikkam Srinivasa , Reddy Paidi Yella , Yum Jun-Ho , Nazeeruddin Mohammad Khaja , Graetzel Michael
Published: August 2011

A new high molar extinction coefficient ruthenium(II) bipyridyl complex “cis-Ru(4,-bis(9,9-dibutyl-7-(3,6-di-tert-butyl-9H-carbazol-9-yl)-9H-fluoren-2-yl)-2,-bipyridine)(2,-bipyridine-4,-dicarboxylic acid)(NCS)2, BPFC” has been synthesized and characterized by FT-IR, -NMR, and ESI-MASS spectroscopes. The sensitizer showed molar extinction coefficient of  M−1cm−1, larger as compared to the reference N719, which showed  M−1cm−1. The test cells fabricated using BPFC sensitizer employing high performance volatile electrolyte, (E01) containing 0.05 M I2, 0.1 M LiI, 0.6 M 1,2-dimethyl-3-n-propylimidazolium iodide, 0.5 M 4-tert-butylpyridine in acetonitrile solvent, exhibited solar-to-electric energy conversion efficiency (η) of 4.65% (short-circuit current density () = 11.52 mA/cm2, open-circuit voltage () = 566 mV, fill factor = 0.72) under Air Mass 1.5 sunlight, lower as compared to the reference N719 sensitized solar cell, fabricated under similar conditions, which exhibited η-value of 6.5% ( = 14.3 mA/cm2, = 640 mV, fill factor = 0.71). UV-Vis measurements conducted on TiO2 films showed decreased film absorption ratios for BPFC as compared to those of reference N719. Staining TiO2 electrodes immediately after sonication of dye solutions enhanced film absorption ratios of BPFC relative to those of N719. Time-dependent density functional theory (TD-DFT) calculations show higher oscillation strengths for 4,-bis(9,9-dibutyl-7-(3,6-di-tert-butyl-9H-carbazol-9-yl)-9H-fluoren-2-yl)-2,-bipyridine relative to 2,-bipyridine-4,-dicarboxylic acid and increased spectral response for the corresponding BPFC complex.
The Electrical Characteristics of Aluminium Doped Zinc Oxide Thin Film for Humidity Sensor Applications
Authors: Md Sin N. D. , Fuad Kamel M. , Alip Rosalena Irma , Mohamad Zulfakri , Rusop M.
Published: August 2011

The electrical characteristics of aluminum (Al) doped zinc oxide (ZnO) thin film for high sensitivity humidity sensors are presented. The effects of Al doping concentration at at % on the Al doped ZnO thin film properties were investigated using current-voltage measurement. The optical and structural properties were characterized using photoluminescence (PL), scanning emission microscope (SEM), and X-ray diffraction (XRD). Parameter 0.6 at % Aluminum doped show high sensitivity and suitable for humidity sensor. PL show an emissions band with two peaks centered at about 380 nm (ultra-violet (UV)) and 600 nm (green) in a room temperature. The length of the nanorods increases as the doping concentration increases. XRD results show the intensity of the (002) peak decreased with the increasing of doping concentration.
Effect of Electroacupuncture on Activation of p38MAPK in Spinal Dorsal Horn in Rats with Complete Freund's Adjuvant-Induced Inflammatory Pain
Authors: Liang Yi , Fang Jian-Qiao , Du Jun-Ying , Fang Jun-Fan
Published: August 2011

Activation of mitogen-activated protein kinases (MAPKs), especially p38 MAPK, plays an important role in the development of central sensitization related to persistent inflammatory pain. Electroacupuncture (EA) is well known to relieve persistent inflammatory pain. However, little is known about relationship between EA and p38 MAPK. Inflammatory pain rat model was induced by intraplantar injection of complete Freund's adjuvant (CFA). Male adult SD rats were randomly divided into the saline group, CFA group, and CFA + EA group. EA (constant saquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA) was applied to bilateral “Zusanli” (ST 36) and “Kunlun” acupoints (BL 60) for 30 min, once per day. The paw edema and paw withdrawal threshold (PWT) were measured at preinjection and days postinjection 1, 3, and 14. Spinal p-p38MAPK- immunoreactivty (p-p38MAPK-IR) cells were detected by immunohistochemistry at postinjection day 3 and 14. EA significantly inhibited paw edema at postinjection days 14 and increased PWT at postinjection days 3 and 14. Moreover, the increasing number of spinal p-p38MAPK-IR cells which was induced by CFA injection was suppressed by EA stimulation. These results indicate that anti-inflammatory and analgesic effect of EA might be associated with its inhibition of spinal p38 MAPK activation and thereby provide a potential mechanism for the treatment of inflammatory pain by EA.
Genetically Lowered Microsomal Epoxide Hydrolase Activity and Tobacco-Related Cancer in 47,000 Individuals
Authors: Lee Julie , Dahl Morten , Nordestgaard Børge G.
Published: August 2011

Background: Two functional polymorphisms of the microsomal epoxide hydrolase (mEH) gene (EPHX1), Tyr113His (rs1051740) and His139Arg (rs2234922), have variably been found to influence susceptibility to various cancer forms. We tested whether genetically lowered mEH activity affects risk of developing cancer in the general population.

Methods: We genotyped 47,089 individuals from the Danish general population for the Tyr113His and His139Arg polymorphisms in the EPHX1 gene and divided them into groups with predicted fast, intermediate, and slow mEH activity. Using Cox proportional hazards models, we calculated HRs for 26 individual cancer diagnoses and for groups of any cancer, tobacco-related cancers, estrogen-related female cancers, and other cancers.

Results: Of the 47,089 individuals, 7,590 experienced a cancer event, and of these, 1,466 were tobacco-related. After multifactorial adjustment, the HRs (95% CI) for tobacco-related cancer were 1.1 (0.8–1.5) and 1.5 (1.1–2.0) in individuals with intermediate and slow mEH activity versus individuals with the fast phenotype (Ptrend = 0.003). The corresponding HRs among ever-smokers were 1.1 (0.8–1.5) and 1.5 (1.1–2.0; Ptrend = 0.003), whereas HRs among never-smokers did not differ from 1.0.

Conclusions: Our results indicate that genetically lowered mEH activity is associated with increased risk of developing tobacco-related cancer among smokers in the general population; however, additional studies are needed to confirm our findings.

Impact: To our knowledge, this is the largest study to investigate the association of mEH phenotype and genotype with tobacco-related cancers combined in the general population. Cancer Epidemiol Biomarkers Prev; 20(8); 1673–82. ©2011 AACR.
The Handling of Missing Data in Molecular Epidemiology Studies
Authors: Desai Manisha , Kubo Jessica , Esserman Denise , Terry Mary Beth
Published: August 2011

Molecular epidemiology studies face a missing data problem, as biospecimen or imaging data are often collected on only a proportion of subjects eligible for study. We investigated all molecular epidemiology studies published as Research Articles, Short Communications, or Null Results in Brief in Cancer Epidemiology, Biomarkers & Prevention from January 1, 2009, to March 31, 2010, to characterize the extent that missing data were present and to elucidate how the issue was addressed. Of 278 molecular epidemiology studies assessed, most (95%) had missing data on a key variable (66%) and/or used availability of data (often, but not always the biomarker data) as inclusion criterion for study entry (45%). Despite this, only 10% compared subjects included in the analysis with those excluded from the analysis and 88% with missing data conducted a complete-case analysis, a method known to yield biased and inefficient estimates when the data are not missing completely at random. Our findings provide evidence that missing data methods are underutilized in molecular epidemiology studies, which may deleteriously affect the interpretation of results. We provide practical guidelines for the analysis and interpretation of molecular epidemiology studies with missing data. Cancer Epidemiol Biomarkers Prev; 20(8); 1571–9. ©2011 AACR.
Age-Period-Cohort Analysis of Primary Bone Cancer Incidence Rates in the United States (1976–2005)
Authors: Anfinsen Kristin P. , Devesa Susan S. , Bray Freddie , Troisi Rebecca , Jonasdottir Thora J. , Bruland Oyvind S. , Grotmol Tom
Published: August 2011

Background: Primary bone cancer comprises three major histologic types: osteosarcoma (OS), Ewing sarcoma (ES), and chondrosarcoma (CS). Given the limited knowledge about the etiology of primary bone cancer, we undertook an age-period-cohort (APC) analysis to determine whether incidence varied by birth cohort or calendar period. The purpose was to examine the temporal development of each bone cancer type and generate etiologic hypotheses via the observed birth cohort-related changes.

Methods: An APC model was fitted to incidence data for U.S. whites for OS, ES, and CS obtained from nine registries of the Surveillance, Epidemiology, and End Results program, which covers about 10% of the U.S. population, 1976–2005.

Results: The incidence of OS decreased between 1976 and 2005 among those aged over 60 years, a decline that occurred among patients with OS as their primary malignancy only. From 1986–1995 to 1996–2005, the incidence rate of CS among females of 20 to 69 years rose by about 50%, with rates increasing among consecutive cohorts born during 1935–1975. CS rates among males were stable, as were rates of ES.

Conclusion: The risk reduction in OS as a primary malignancy at older ages could possibly be related to diminished exposure over time to bone-seeking radionuclides. The CS increase among females corresponds to birth cohorts with rising exposures to oral contraceptives and menopausal hormonal therapy.

Impact: As the estrogen signaling pathway has been shown to stimulate proliferation of normal and malignant chondrocytes, estrogen exposure may increase the risk for CS. Further studies are warranted to clarify its possible etiological significance. Cancer Epidemiol Biomarkers Prev; 20(8); 1770–7. ©2011 AACR.
Tobacco Smoking and Cutaneous Squamous Cell Carcinoma: A 16-Year Longitudinal Population-Based Study
Authors: McBride Penelope , Olsen Catherine M. , Green Adèle C.
Published: August 2011

Background: Although tobacco smoking is commonly cited as a risk factor for cutaneous squamous cell carcinoma (SCC), the evidence from previous clinical and case–control studies is conflicting. We therefore aimed to prospectively examine the role of tobacco smoking in the development of SCC of the skin in a population-based study.

Methods: Study participants were 1,287 adults aged 25 to 75 years in 1992, randomly selected from the Nambour community, with no previous history of SCC. Standard skin pigment and sun-sensitivity profiles were obtained at baseline. Detailed prospective information on sun exposure, smoking, and skin cancer occurrence (histologically confirmed) was collected over a 16-year period, 1992 to 2007.

Results: Of 1,287 participants, 43% were male and average age was 48 years. A total of 188 first cutaneous SCCs were identified during the study period. After adjustment for other known risk factors, neither former nor current smokers were at raised risk of SCC: relative risk (RR) = 1.1, 95% CI: 0.8–1.5 and RR = 1.1, 95% CI: 0.7–1.5, respectively, compared with lifelong nonsmokers, nor were there any dose–response relationships with amount smoked or duration of smoking and risk of SCC.

Conclusions: In this Australian follow-up study, tobacco smoking did not increase the risk of SCC of the skin.

Impact: These prospective adjusted data provide strong evidence which suggests that cutaneous SCC should not be on the list of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev; 20(8); 1778–83. ©2011 AACR.
Gender Disparities in the Tumor Genetics and Clinical Outcome of Multiple Myeloma
Authors: Boyd Kevin D. , Ross Fiona M. , Chiecchio Laura , Dagrada GianPaolo , Konn Zoe J. , Tapper William J. , Walker Brian A. , Wardell Christopher P. , Gregory Walter M. , Szubert Alex J. , Davies Faith E. , Morgan Gareth J.
Published: August 2011

Background: Several cancer types have differences in incidence and clinical outcome dependent on gender, but these are not well described in myeloma. The aim of this study was to characterize gender disparities in myeloma.

Methods: We investigated the association of gender with the prevalence of tumor genetic lesions and the clinical outcome of 1,960 patients enrolled in the phase III clinical trial MRC Myeloma IX. Genetic lesions were characterized by FISH.

Results: Disparities were found in the prevalence of primary genetic lesions with immunoglobulin heavy chain gene (IGH) translocations being more common in women (50% of female patients vs. 38% of male patients, P < 0.001) and hyperdiploidy being more common in men (50% female vs. 62% male, P < 0.001). There were also differences in secondary genetic events with del(13q) (52% female vs. 41% male, P < 0.001) and +1q (43% female vs. 36% male, P = 0.042) being found more frequently in female myeloma patients. Female gender was associated with inferior overall survival (median: 44.8 months female vs. 49.9 months male, P = 0.020).

Conclusions: We found gender-dependent differences in the prevalence of the primary genetic events of myeloma, with IGH translocations being more common in women and hyperdiploidy more common in men. This genetic background may impact subsequent genetic events such as +1q and del(13q), which were both more frequent in women. The higher prevalence of lesions associated with poor prognosis in the female myeloma population, such as t(4;14), t(14;16) and +1q, may adversely affect clinical outcome.

Impact: These differences suggest that gender influences the primary genetic events of myeloma. Cancer Epidemiol Biomarkers Prev; 20(8); 1703–7. ©2011 AACR.
Sex Disparities in Cancer Mortality and Survival
Authors: Cook Michael B. , McGlynn Katherine A. , Devesa Susan S. , Freedman Neal D. , Anderson William F.
Published: August 2011

Background: Previous research has noted higher cancer mortality rates and lower survival among males than females. However, systematic comparisons of these two metrics by sex have been limited.

Methods: We extracted U.S. vital rates and survival data from the Surveillance, Epidemiology and End Results Database for 36 cancers by sex and age for the period 1977 to 2006. We compared sex-specific mortality rates and examined male-to-female mortality rate ratios (MRR). We also extracted case data which included age and date of diagnosis, sex, primary cancer site, tumor stage and grade, survival time, vital status, and cause of death. Relative cancer-specific HRs for death in the 5-year period following diagnosis were estimated with Cox proportional hazards models, adjusted for covariates.

Results: For the vast majority of cancers, age-adjusted mortality rates were higher among males than females with the highest male-to-female MRR for lip (5.51), larynx (5.37), hypopharynx (4.47), esophagus (4.08), and urinary bladder (3.36). Cancer-specific survival was, for most cancers, worse for males than females, but such disparities were drastically less than corresponding MRRs [e.g., lip (HR = 0.93), larynx (HR = 1.09), hypopharynx (HR = 0.98), esophagus (HR = 1.05), and urinary bladder (HR = 0.83)].

Conclusions: Male-to-female MRRs differed markedly while cancer survival disparities were much less pronounced. This suggests that sex-related cancer disparities are more strongly related to etiology than prognosis.

Impact: Future analytic studies should attempt to understand causes of observed sex disparities in cancer. Cancer Epidemiol Biomarkers Prev; 20(8); 1629–37. ©2011 AACR.
Do Community Health Worker Interventions Improve Rates of Screening Mammography in the United States? A Systematic Review
Authors: Wells Kristen J. , Luque John S. , Miladinovic Branko , Vargas Natalia , Asvat Yasmin , Roetzheim Richard G. , Kumar Ambuj
Published: August 2011

Background: Community health workers (CHW) are lay individuals who are trained to serve as liaisons between members of their communities and health care providers and services.

Methods: A systematic review was conducted to synthesize evidence from all prospective controlled studies on effectiveness of CHW programs in improving screening mammography rates. Studies reported in English and conducted in the United States were included if they: (i) evaluated a CHW intervention designed to increase screening mammography rates in women 40 years of age or older without a history of breast cancer; (ii) were a randomized controlled trial (RCT), case–controlled study, or quasi-experimental study; and (iii) evaluated a CHW intervention outside of a hospital setting.

Results: Participation in a CHW intervention was associated with a statistically significant increase in receipt of screening mammography [risk ratio (RR): 1.06 (favoring intervention); 95% CI: 1.02–1.11, P = 0.003]. The effect remained when pooled data from only RCTs were included in meta-analysis (RR: 1.07; 95% CI: 1.03–1.12, P = 0.0005) but was not present using pooled data from only quasi-experimental studies (RR: 1.03; 95% CI: 0.89–1.18, P = 0.71). In RCTs, participants recruited from medical settings (RR: 1.41; 95% CI: 1.09–1.82, P = 0.008), programs conducted in urban settings (RR: 1.23; 95% CI: 1.09, 1.39, P = 0.001), and programs where CHWs were matched to intervention participants on race or ethnicity (RR: 1.58, 95% CI: 1.29–1.93, P = 0.0001) showed stronger effects on increasing mammography screening rates.

Conclusions: CHW interventions are effective for increasing screening mammography in certain settings and populations.

Impact: CHW interventions are especially associated with improvements in rate of screening mammography in medical settings, urban settings, and in participants who are racially or ethnically concordant with the CHW. Cancer Epidemiol Biomarkers Prev; 20(8); 1580–98. ©2011 AACR.
Vitamin D-Related Genetic Variants, Interactions with Vitamin D Exposure, and Breast Cancer Risk among Caucasian Women in Ontario
Authors: Anderson Laura N. , Cotterchio Michelle , Cole David E. C. , Knight Julia A.
Published: August 2011

Background: Vitamin D, from diet and sunlight exposure, may be associated with reduced breast-cancer risk. This study investigated if candidate gene variants in vitamin D pathways are associated with breast cancer risk, or modify the associations between breast cancer and vitamin D exposure.

Methods: Breast cancer cases aged 25 to 74 years were identified from the Ontario Cancer Registry (histopathologically confirmed and diagnosed 2002–2003) and population-based controls were identified through random digit dialing of Ontario households. Saliva (DNA) was available for 1,777 cases and 1,839 controls. Multivariate logistic regression was used to evaluate associations between 19 single nucleotide polymorphisms (SNP) in vitamin D related genes, including vitamin D binding protein (GC), vitamin D receptor (VDR), and cytochrome P450 type 24A1 (CYP24A1). Statistical interactions were assessed using the likelihood ratio test.

Results: Some SNPs were found to be significantly associated with breast cancer risk. For example, breast cancer risk was associated with the GC rs7041 TT genotype (age-adjusted odds ratio (OR) = 1.23; 95% CI: 1.01, 1.51) and inversely with the VDR Fok1 (rs2228570) ff genotype (OR = 0.71; 95% CI: 0.57, 0.88). Few significant gene-environment interactions were observed between dietary vitamin D and genetic variants.

Conclusion: Our study suggests certain vitamin D related genetic variants may influence breast-cancer risk and we found limited evidence that genetic variants modify the associations between vitamin D exposure and breast cancer risk.

Impact: Variation in vitamin D-related genotypes may help to explain inconsistent results from previous epidemiologic studies and may lead to targeted prevention strategies. Cancer Epidemiol Biomarkers Prev; 20(8); 1708–17. ©2011 AACR.
Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas
Authors: de Vogel Stefan , Schneede Jörn , Ueland Per Magne , Vollset Stein Emil , Meyer Klaus , Fredriksen Åse , Midttun Øivind , Bjørge Tone , Kampman Ellen , Bretthauer Michael , Hoff Geir
Published: August 2011

Background: Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no previous studies relating plasma concentrations of methionine, choline, and betaine to this outcome.

Methods: This study comprised 10,601 individuals, 50 to 64 years of age, participating in the Norwegian Colorectal Cancer Prevention (NORCCAP) screening study. Using logistic regression analyses, we crosssectionally investigated associations between distal colorectal adenoma occurrence–potential precursor lesions of colorectal carcinomas–and plasma concentrations of methyl group donors and B-vitamins, and polymorphisms of genes related to one-carbon metabolism.

Results: Screening revealed 1,809 subjects (17.1%) with at least one adenoma. The occurrence of high-risk adenomas (observed in 421 subjects) was inversely associated with plasma concentrations of methionine (highest versus lowest quartile: odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.45–0.83), betaine: OR = 0.74; 95% CI = 0.54–1.02, the vitamin B2 form flavin-mononucleotide (FMN): OR = 0.65; 95% CI = 0.49–0.88, and the vitamin B6 form pyridoxal 5′-phosphate (PLP): OR = 0.69; 95% CI = 0.51–0.95, but not with folate, choline, vitamin B12 concentrations, or with the studied polymorphisms. High methionine concentration in combination with high vitamin B2 or B6 concentrations was associated with lower occurrence of high-risk adenomas compared with these factors individually.

Conclusions: High plasma concentrations of methionine and betaine, and vitamins B2 and B6 may reduce risk of developing colorectal adenomas.

Impact: In addition to B-vitamins, methyl group donors such as methionine and betaine may play a role in colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(8); 1726–35. ©2011 AACR.
Incomplete Data: What You Don't Know Might Hurt You
Authors: Heitjan Daniel F.
Published: August 2011

Molecular epidemiology studies commonly exhibit missing observations. Methods for extracting correct and efficient analyses from incomplete data are well known in statistics, but relatively few such methods have diffused into applications. I review some areas of incomplete data research that are relevant to molecular epidemiology and appeal for greater efforts by statisticians to translate their methods into practice. Cancer Epidemiol Biomarkers Prev; 20(8); 1567–70. ©2011 AACR.
Circulation: Cardiovascular Genetics
Editors' Picks
Authors:   The Editors
Published: August 2011

The following articles are being highlighted as part of
Circulation's
Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in
Circulation
and the
Circulation
subspecialty journals. The studies included in this article represent the “Editors' Picks” for each issue of
Circulation: Cardiovascular Genetics
published in 2009 and 2010.