bluuebunny/crossref_metadata_2025 huggingface dataset:
BIOMIMETIC ELECTROSPUN GELATIN–CHITOSAN POLYURETHANE FOR HEART VALVE LEAFLETS
Authors: WONG CYNTHIA , SHITAL PATEL , CHEN RUI , OWIDA AMAL , MORSI YOS
Published: September 2010

Native heart valve leaflets are subjected to continuous pulsatile and homodynamic forces and can be as thin as 300 μm. For a proper function of the valve the materials selected for the leaflets need to be biocompatible, robust, flexible, and have comparable mechanical properties to the natural ones.

In this paper, biocompatibility and cell retention ability for gelatin–chitosan polyurethane (PU), polyglycolide (PGA)/PLA and collagen-coated bovine pericardium were examined and their mechanical properties were tested. Endothelial cells, isolated from ovine carotid arteries were seeded onto these materials and exposed to a range of shear-stresses for a period of 1–3 h.

The findings indicated that throughout the exposure time and the shear-stress range tested, a mean cell retention rate of 80% was obtained in the gelatin–chitosan PU group. However, for PGA/PLA and pericardium groups it was found that as the exposure time of shear-stress increased, a significant cell reduction was observed. Noticeably for all the range of physiological flow conditions tested, the electrospun gelatin–chitosan PU demonstrated good biocompatibility and cell retention properties and could be potentially used as a biomaterial for tissue engineering of heart valves.
CABG MODELS FLOW SIMULATION STUDY ON THE EFFECTS OF VALVE REMNANTS IN THE VENOUS GRAFT
Authors: KABINEJADIAN FOAD , CHUA LEOK POH , GHISTA DHANJOO N. , TAN YONG SENG
Published: September 2010

Venous valves and sinuses are frequently observed in vein grafts in the coronary artery bypass grafts (CABG). However, from the biomedical engineering viewpoint, vein grafts are always assumed as smooth tubes in the existing simulations, and no effort has been made to investigate the effects of jaggedness of the graft inner wall due to the valve cusps remnants and valve sinus (in case of valve-stripped saphenous vein (SV) grafts) on the blood flow patterns and hemodynamic parameters (HPs). In this paper, the effects of the inner surface irregularities of a vein graft on the blood flow is investigated in the graft as well as in the distal anastomotic region, with a more realistic geometry of valve-stripped SV, by means of numerical simulation of pulsatile, Newtonian blood flow. The simulation results demonstrate that the valve remnants and sinuses cause disturbances in the flow field within the graft (due to vortices formation within the valve sinuses) and undesirable distribution of HPs, which can result in early atherosclerotic lesion development in the graft.
BENEFICIAL EFFECTS OF EXOGENOUS CROSSLINKING AGENTS ON SELF-ASSEMBLED TISSUE ENGINEERED CARTILAGE CONSTRUCT BIOMECHANICAL PROPERTIES
Authors: ELDER BENJAMIN D. , MOHAN ARVIND , ATHANASIOU KYRIACOS A.
Published: September 2010

Background. As articular cartilage is unable to repair itself, there is a tremendous clinical need for a tissue engineered replacement tissue. Current tissue engineering efforts using the self-assembly process have demonstrated promising results, but the biomechanical properties remain at roughly 50% of native tissue. Methodology/Principal Findings. The objective of this study was to determine the feasibility of using exogenous crosslinking agents to enhance the biomechanical properties of a scaffoldless cartilage tissue engineering approach. Four crosslinking agents (glutaraldehyde, ribose, genipin, and methylglyoxal) were applied each at a single concentration and single application time. It was determined that ribose application resulted in a significant 69% increase in Young's modulus, a significant 47% increase in ultimate tensile strength, as well as a trend toward a significant increase in aggregate modulus. Additionally, methylglyoxal application resulted in a significant 58% increase in Young's modulus. No treatments altered the biochemical content of the tissue. Conclusions/Significance. To our knowledge, this is the first study to examine the use of exogenous crosslinking agents on any tissue formed using a scaffoldless tissue engineering approach. In particular, this study demonstrates that a one-time treatment with crosslinking agents can be employed effectively to enhance the biomechanical properties of tissue engineered articular cartilage. The results are exciting, as they demonstrate the feasibility of using exogenous crosslinking agents to enhance the biomechanical properties without the need for increased glycosaminoglycan (GAG) and collagen content.
TIME-FREQUENCY CHARACTERIZATION OF FETAL PHONOCARDIOGRAPHIC SIGNALS USING WAVELET SCALOGRAM
Authors: CHOURASIA VIJAY S. , TIWARI ANIL K. , GANGOPADHYAY RANJAN
Published: September 2010

Fetal phonocardiography is a simple and noninvasive diagnostic technique for surveillance of fetal well-being. The fetal phonocardiographic (fPCG) signals carry valuable information about the anatomical and physiological states of the fetal heart. This article is concerned with a study of continuous wavelet transform (CWT)-based scalogram in analyzing the fPCG signals. The scalogram has both spatial and frequency resolution powers, whereas traditional spectral estimation methods only have the frequency resolution ability. The fPCG signals are acquired by a specially developed data recording system. Segmentation of these signals into fundamental components of fetal heart sound (S1 & S2) is carried out through envelope detection and thresholding techniques. CWT-based scalogram is used for time-frequency characterization of the segmented fPCG signals. It has been shown that the wavelet scalogram provides enough features of the fPCG signals that will help to obtain qualitative and quantitative measurements of the time-frequency characteristics of the fPCG signals and consequently, assist in diagnosis. The proposed method for time-frequency analysis (TFA) and the associated pre-processing have been shown to be suitable for the characterization of fPCG signals, yielding relatively good and robust results in the experimental evaluation.
APPLICATION OF HOMOTOPY PERTURBATION AND VARIATIONAL ITERATION METHODS TO SIR EPIDEMIC MODEL
Authors: GHOTBI ABDOUL R. , BARARI A. , OMIDVAR M. , DOMAIRRY G.
Published: September 2010

Children born are susceptible to various diseases such as mumps and chicken pox. These diseases are the most common form of infectious diseases. In recent years, scientists have been trying to devise strategies to fight against these diseases. Since vaccination is considered the most effective strategy against childhood diseases, the development of the framework that would predict the optimal vaccine coverage level needed to prevent the spread of diseases is crucial. The SIR model is a standard compartmental model that has been used to describe many epidemiological diseases. In this article, two methods namely homotopy perturbation method (HPM) and variational iteration method (VIM) are employed to compute an approximation to the solution of nonlinear system of differential equations governing the problem. The obtained results are compared with those obtained by Adomian decomposition method (ADM). This research reveals that although the obtained results are the same, HPM and VIM are much more robust, more convenient and efficient in comparison to ADM.
ALGORITHM FOR AUTOMATIC DETECTION OF ECG WAVES
Authors: NABIL DIB. , BEREKSI-REGUIG F.
Published: September 2010

An accurate measurement of the different electrocardiogram (ECG) intervals is dependent on the accurate identification of the beginning and the end of the P, QRS, and T waves. Available commercial systems provide a good QRS detection accuracy. However, the detection of the P and T waves remains a serious challenge due to their widely differing morphologies in normal and abnormal beats. In this paper, a new algorithm for the detection of the QRS complex as well as for P and T waves identification is provided. The proposed algorithm is based on different approaches and methods such as derivations, thresholding, and surface indicator. The proposed algorithm is tested and evaluated on ECG signals from the universal MIT-BIH database. It shows a good ability to detect P, QRS, and T waves for different cases of ECG signal even in very noisy conditions. The obtained QRS, sensitivity and positive predictivity are respectively 95.39% and 98.19%. The developed algorithm is also able to separate the overlapping P and T waves.
RISK PREFERENCE AND SEQUENTIAL CHOICE IN EVOLUTIONARY GAMES
Authors: ROOS PATRICK , NAU DANA
Published: September 2010

There is much empirical evidence that human decision-making under risk does not coincide with expected value maximization, and much effort has been invested into the development of descriptive theories of human decision-making involving risk (e.g. Prospect Theory). An open question is how behavior corresponding to these descriptive models could have been learned or arisen evolutionarily, as the described behavior differs from expected value maximization. We believe that the answer to this question lies, at least in part, in the interplay between risk-taking, sequentiality of choice, and population dynamics in evolutionary environments. In this paper, we provide the results of several evolutionary game simulations designed to study the risk behavior of agents in evolutionary environments. These include several evolutionary lottery games where sequential decisions are made between risky and safe choices, and an evolutionary version of the well-known stag hunt game. Our results show how agents that are sometimes risk-prone and sometimes risk-averse can outperform agents that make decisions solely based on the maximization of the local expected values of the outcomes, and how this can facilitate the evolution of cooperation in situations where cooperation entails risk.
COMPETITION AND THE DYNAMICS OF GROUP AFFILIATION
Authors: GEARD NICHOLAS , BULLOCK SETH
Published: September 2010

How can we understand the interaction between the social network topology of a population and the patterns of group affiliation in that population? Each aspect influences the other: social networks provide the conduits via which groups recruit new members and groups provide the context in which new social ties are formed. Given that the resources of individuals are finite, groups can be considered to compete with one another for the time and energy of their members. Such competition is likely to have an impact on the way in which social structure and group affiliation co-evolve. While many social simulation models exhibit group formation as a part of their behaviour (e.g., opinion clusters or converged cultures), models that explicitly focus on group affiliation are less common. We describe and explore the behaviour of a model in which, distinct from most current models, individual nodes can belong to multiple groups simultaneously. By varying the capacity of individuals to belong to groups, and the costs associated with group membership, we explore the effect of different levels of competition on population structure and group dynamics.
Depth Profiles of Cu Centers in Silicon Crystals Deposited with Cu and Diffused between 400 and 1000 °C Measured by Deep-Level Transient Spectroscopy
Authors: Nakamura Minoru , Murakami Susumu
Published: September 2010

For Cu-deposited Si crystals, we observed markedly different formation behavior of Cu-related species between samples that diffused below and above the eutectic temperature (EUT; 802 °C) of the Si–Cu system. The Cu center denoted as the CuDLB center was the dominant species under the Cu silicide layer and was almost homogenously distributed in the bulk of the samples that diffused below the EUT. For the samples that diffused above the EUT, the center concentration was markedly low near the surface due to the out-diffusion of Cu and gradually increased before forming a plateau in the region deeper than 30 µm from the surface.
Evaluation of Interface Property and DC Characteristics Enhancement in Nanoscale n-Channel Metal–Oxide–Semiconductor Field-Effect Transistor Using Stress Memorization Technique
Authors: Huang Po Chin , Wu San Lein , Chang Shoou Jinn , Huang Yao Tsung , Kuo Cheng Wen , Chang Ching Yao , Cheng Yao Chin , Cheng Osbert
Published: September 2010

In this letter, the advanced 40 nm technology n-channel metal–oxide–semiconductor field-effect transistor devices using the stress memorization technique (SMT) are presented. We demonstrate that SMT process would not affect the electrical characteristics of devices and can introduce higher tensile stress on channels, which enhances drive current. Through charge pumping measurement, it can be verified that SMT does not affect Si/SiO2interface quality. Moreover, SMT-induced higher tensile stress decreases not only scattering coefficient but also tunneling attenuation length, resulting in smaller input-referred noise, which represents an intrinsic advantage of low-frequency noise performance.
Evolution of Lactation: Ancient Origin and Extreme Adaptations of the Lactation System
Authors: Lefèvre Christophe M. , Sharp Julie A. , Nicholas Kevin R.
Published: September 2010

Lactation, an important characteristic of mammalian reproduction, has evolved by exploiting a diversity of strategies across mammals. Comparative genomics and transcriptomics experiments have now allowed a more in-depth analysis of the molecular evolution of lactation. Milk cell and mammary gland genomic studies have started to reveal conserved milk proteins and other components of the lactation system of monotreme, marsupial, and eutherian lineages. These analyses confirm the ancient origin of the lactation system and provide useful insight into the function of specific milk proteins in the control of lactation. These studies also illuminate the role of milk in the regulation of growth and development of the young beyond simple nutritive aspects.
Contrasting Methods of Quantifying Fine Structure of Human Recombination
Authors: Clark Andrew G. , Wang, Xu , Matise Tara
Published: September 2010

There has been considerable excitement over the ability to construct linkage maps based only on genome-wide genotype data for single nucleotide polymorphic sites (SNPs) in a population sample. These maps, which are derived from estimates of linkage disequilibrium (LD), rely on population genetics theory to relate the decay of LD to the local rate of recombination, but other population processes also come into play. Here we contrast these LD maps to the classically derived, pedigree-based human recombination maps. The LD maps have a level of resolution greatly exceeding that of the pedigree maps, and at this fine scale, sperm typing allows a means of validation. While at a gross level both the pedigree maps and the sperm typing methods generally agree with LD maps, there are significant local differences between them, and the fact that these maps measure different genetic features should be remembered when using them for other genetic inferences.
Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome
Authors: Dekker Mark J. , Su Qiaozhu , Baker Chris , Rutledge Angela C. , Adeli Khosrow
Published: September 2010

As dietary exposure to fructose has increased over the past 40 years, there is growing concern that high fructose consumption in humans may be in part responsible for the rising incidence of obesity worldwide. Obesity is associated with a host of metabolic challenges, collectively termed the metabolic syndrome. Fructose is a highly lipogenic sugar that has profound metabolic effects in the liver and has been associated with many of the components of the metabolic syndrome (insulin resistance, elevated waist circumference, dyslipidemia, and hypertension). Recent evidence has also uncovered effects of fructose in other tissues, including adipose tissue, the brain, and the gastrointestinal system, that may provide new insight into the metabolic consequences of high-fructose diets. Fructose feeding has now been shown to alter gene expression patterns (such as peroxisome proliferator-activated receptor-γ coactivator-1α/β in the liver), alter satiety factors in the brain, increase inflammation, reactive oxygen species, and portal endotoxin concentrations via Toll-like receptors, and induce leptin resistance. This review highlights recent findings in fructose feeding studies in both human and animal models with a focus on the molecular and biochemical mechanisms that underlie the development of insulin resistance, hepatic steatosis, and the metabolic syndrome.
Odyssey between Scylla and Charybdis through storms of carbohydrate metabolism and diabetes: a career retrospective
Authors: Vranic Mladen
Published: September 2010

This research perspective allows me to summarize some of my work completed over 50 years, and it is organized in seven sections. 1) The treatment of diabetes concentrates on the liver and/or the periphery. We quantified hormonal and metabolic interactions involved in physiology and the pathogenesis of diabetes by developing tracer methods to separate the effects of diabetes on both. We collaborated in the first tracer clinical studies on insulin resistance, hypertriglyceridemia, and the Cori cycle. 2) Diabetes reflects insulin deficiency and glucagon abundance. Extrapancreatic glucagon changed the prevailing dogma and permitted precise exploration of the roles of insulin and glucagon in physiology and diabetes. 3) We established the critical role of glucagon-insulin interaction and the control of glucose metabolism during moderate exercise and of catecholamines during strenuous exercise. Deficiencies of the release and effects of these hormones were quantified in diabetes. We also revealed how acute and chronic hyperglycemia affects the expression of GLUT2 gene and protein in diabetes. 4) We outlined molecular and physiological mechanisms whereby exercise training and repetitive neurogenic stress can prevent diabetes in ZDF rats. 5) We and others established that the indirect effect of insulin plays an important role in the regulation of glucose production in dogs. We confirmed this effect in humans and demonstrated that in type 2 diabetes it is mainly the indirect effect. 6) We indicated that the muscle and the liver protected against glucose changes. 7) We described molecular mechanisms responsible for increased HPA axis in diabetes and for the diminished responses of HPA axis, catecholamines, and glucagon to hypoglycemia. We proposed a new approach to decrease the threat of hypoglycemia.
Two New Types of Rings Defined by Using a Translational Invariant Fuzzy Subset
Authors: Ghanem Manal
Published: September 2010

We use a translational invariant fuzzy subset of a ring to define two new types of commutative rings namely, -presimplifiable and -associate rings. We present some results of these rings. The interest of these results is that most of them are mirrors of corresponding results of presimplifiable and associate rings in classical ring theory.
Treatment of Hepatitis C Infections with Interferon: A Historical Perspective
Authors: Friedman Robert M. , Contente Sara
Published: September 2010

Interferons were first described in 1957, but it was not until 34
years after their discovery that sufficient quantities of it were
available for treatment of hepatitis C virus (HCV) infections,
Clinicians now have an excellent understanding of the basis for
the effectiveness of interferon alpha (IFN-) in the therapy of
this disease. Treatment with IFN- is more efficient when it
complemented by the antiviral ribavirin and the IFN- is conjugated
with polyethylene glycol to form peginterferon. In the near future
treatment of HCV with IFN- may involve new anti-HCV agents that
are currently under development.
Associative Models for Storing and Retrieving Concept Lattices
Authors: Acevedo María Elena , Yáñez-Márquez Cornelio , Acevedo Marco Antonio
Published: September 2010

Alpha‐beta bidirectional associative memories are implemented for storing concept lattices. We use Lindig′s algorithm to construct a concept lattice of a particular context; this structure is stored into an associative memory just as a human being does, namely, associating patterns. Bidirectionality and perfect recall of Alpha‐Beta associative model make it a great tool to store a concept lattice. In the learning phase, objects and attributes obtained from Lindig′s algorithm are associated by Alpha‐Beta bidirectional associative memory; in this phase the data is stored. In the recalling phase, the associative model allows to retrieve objects from attributes or vice versa. Our model assures the recalling of every learnt concept.
Exercise Testing and Prescription in Patients with Congenital Heart Disease
Authors: ten Harkel A. D. J. , Takken T.
Published: September 2010

The present paper provides a review of the literature regarding exercise testing, exercise capacity, and the role of exercise training in patients with congenital heart disease (CHD). Different measures of exercise capacity are discussed, including both simple and more advanced exercise parameters. Different groups of patients, including shunt lesions, pulmonary valvar stenosis, patients after completion of Fontan circulation, and patients with pulmonary arterial hypertension are discussed separately in more detail. It has been underscored that an active lifestyle, taking exercise limitations and potential risks of exercise into account is of utmost importance. Increased exercise capacity in these patients is furthermore correlated with an improvement of objective and subjective quality of life.
SPECT/CT for Lymphatic Mapping of Sentinel Nodes in Early Squamous Cell Carcinoma of the Oral Cavity and Oropharynx
Authors: Stephan K. Haerle , Sandro J. Stoeckli
Published: September 2010

Adequate staging and treatment of the neck in squamous cell carcinoma of the oral cavity and oropharynx (OSCC) is of paramount importance. Elective neck dissection (END) of the clinical N0-neck is widely advocated as neck treatment. With regard to the prevalence of 20–40% of occult neck metastases found in the ND specimens, the majority of patients undergo surgery of the lymphatic drainage basin without therapeutic benefit. Sentinel node biopsy (SNB) has been shown to be a safe, reliable and accurate alternative treatment modality for selected patients. Using this technique, lymphatic mapping is crucial. Previous reports suggested a benefit of single photon emission computed tomography with CT (SPECT/CT) over dynamic planar lymphoscintigraphy (LS) alone. SPECT/CT allows the surgeon for better topographical orientation and delineation of sentinel lymph nodes (SLN’s) against surrounding structures. Additionally, SPECT/CT has the potential to detect more SLN’s which might harbour occult disease, than LS. SPECT/CT is recommended to be used routinely, although SPECT/CT is not indispensable for successful SNB.
High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123) for Extraskeletal Ewing's Sarcoma: A Case Report
Authors: Sakabe Tomoya , Murata Hiroaki , Konishi Eiichi , Koto Kazutaka , Horie Naoyuki , Matsui Takaaki , Sawai Yasushi , Yamazaki Hideya , Kagiya Tsutomu V. , Kubo Toshikazu
Published: September 2010

Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123) contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment.
Colorectal Tumors Are Effectively Eradicated by Combined Inhibition of β-Catenin, KRAS, and the Oncogenic Transcription Factor ITF2
Authors: Mologni Luca , Dekhil Hafedh , Ceccon Monica , Purgante Stefania , Lan Cathy , Cleris Loredana , Magistroni Vera , Formelli Franca , Gambacorti-Passerini Carlo B.
Published: September 2010

Colorectal carcinomas (CRC) harbor well-defined genetic abnormalities, including aberrant activation of β-catenin (β-cat) and KRAS, but independent targeting of these molecules seems to have limited therapeutic effect. In this study, we report therapeutic effects of combined targeting of different oncogenes in CRC. Inducible short hairpin RNA (shRNA)–mediated silencing of β-cat, ITF2, or KRAS decreased proliferation by 88%, 72%, and 45%, respectively, with no significant apoptosis in any case. In contrast, combined blockade of β-cat and ITF2 inhibited proliferation by 99% with massive apoptosis. Similar effects occurred after combined shRNA against β-cat and KRAS. In vivo, single oncogene blockade inhibited the growth of established tumors by up to 30%, whereas dual β-cat and ITF2 targeting caused 93% inhibition. Similar tumor growth suppression was achieved by double β-cat/KRAS shRNA in vivo. Our findings illustrate an effective therapeutic principle in CRC based on a combination targeting strategy that includes the ITF2 oncogene, which represents a novel therapeutic target. Cancer Res; 70(18); 7253–63. ©2010 AACR.
Prevalence of Human Papillomavirus Types in High-Grade Cervical Intraepithelial Neoplasia and Cancer in Italy
Authors: Carozzi Francesca M. , Tornesello Maria L. , Burroni Elena , Loquercio Giovanna , Carillo Giuseppe , Angeloni Claudio , Scalisi Aurora , Macis Rosalba , Chini Francesco , Buonaguro Franco M. , Giorgi Rossi Paolo ,   for the HPV Prevalence Italian Working Group
Published: September 2010

Background: The aim of this multicentric study was to identify human papillomavirus (HPV) type distribution in invasive cervical cancer and high-grade cervical intraepithelial neoplasia 2/3 (CIN2/3) in Italy.

Methods: Cases were sampled through the electronic databases at the pathology units of eight centers in six regions from central and southern Italy. HPV types were detected from paraffin-embedded tissue samples and cervical specimens through amplification of HPV DNA with GP5+/GP6+ primers, followed by genotyping with reverse line blot (RLB). Untyped HPV-positive samples were sequenced. HPV-negative samples underwent nested PCR, followed by either RLB or sequencing. Finally, the remaining HPV-negative samples were amplified with primers targeting the virus E6 to E7 regions.

Results: From 1,162 cases initially selected, 722 samples were further analyzed: 144 CIN2, 385 CIN3, 157 invasive squamous carcinomas, and 36 adenocarcinomas. Samples (6.9%) were HPV negative. The proportion of HPV16/18 was 60.8%, 76.6%, and 78.8% in CIN2, CIN3, and invasive cancers, respectively (P trend = 0.004). There was a significant decreasing trend of HPV16/18 with age in invasive cancers, going from 92% in women <35 years to 73% in women >55 years (P = 0.036). The proportion of coinfections was 16.8%, 15.5%, and 10.0% in CIN2, CIN3, and invasive cancers, respectively (P trend = 0.07).

Conclusions: The proportion of invasive cancers caused by HPV16/18 decreases with age at diagnosis.

Impact: The absolute risk of an invasive cancer due to non-HPV16/18 in women under 35 is extremely low. This finding might prompt us to rise the age at which public HPV screening for vaccinated women should start. Cancer Epidemiol Biomarkers Prev; 19(9); 2389–400. ©2010 AACR.
Missense Variants in ATM in 26,101 Breast Cancer Cases and 29,842 Controls
Authors: Fletcher Olivia , Johnson Nichola , dos Santos Silva Isabel , Orr Nick , Ashworth Alan , Nevanlinna Heli , Heikkinen Tuomas , Aittomäki Kristiina , Blomqvist Carl , Burwinkel Barbara , Bartram Claus R. , Meindl Alfons , Schmutzler Rita K. , Cox Angela , Brock Ian , Elliott Graeme , Reed Malcolm W.R. , Southey Melissa C. , Smith Letitia , Spurdle Amanda B. , Hopper John L. , Couch Fergus J. , Olson Janet E. , Wang Xianshu , Fredericksen Zachary , Schürmann Peter , Waltes Regina , Bremer Michael , Dörk Thilo , Devilee Peter , van Asperen Christie J. , Tollenaar Rob A.E.M. , Seynaeve Caroline , Hall Per , Czene Kamila , Humphreys Keith , Liu Jianjun , Ahmed Shahana , Dunning Alison M. , Maranian Melanie , Pharoah Paul D.P. , Chenevix-Trench Georgia , Beesley Jonathan , Bogdanova Natalia V. , Antonenkova Natalia N. , Zalutsky Iosif V. , Anton-Culver Hoda , Ziogas Argyrios , Brauch Hiltrud , Ko Yon-Dschun , Hamann Ute , Fasching Peter A. , Strick Reiner , Ekici Arif B. , Beckmann Matthias W. , Giles Graham G. , Severi Gianluca , Baglietto Laura , English Dallas R. , Milne Roger L. , Benítez Javier , Arias José Ignacio , Pita Guillermo , Nordestgaard Børge G. , Bojesen Stig E. , Flyger Henrik , Kang Daehee , Yoo Keun-Young , Noh Dong Young , Mannermaa Arto , Kataja Vesa , Kosma Veli-Matti , García-Closas Montserrat , Chanock Stephen , Lissowska Jolanta , Brinton Louise A. , Chang-Claude Jenny , Wang-Gohrke Shan , Broeks Annegien , Schmidt Marjanka K. , van Leeuwen Flora E. , Van't Veer Laura J. , Margolin Sara , Lindblom Annika , Humphreys Manjeet K. , Morrison Jonathan , Platte Radka , Easton Douglas F. , Peto Julian
Published: September 2010

Background: Truncating mutations in ATM have been shown to increase the risk of breast cancer but the effect of missense variants remains contentious.

Methods: We have genotyped five polymorphic (minor allele frequency, 0.9-2.6%) missense single nucleotide polymorphisms (SNP) in ATM (S49C, S707P, F858L, P1054R, and L1420F) in 26,101 breast cancer cases and 29,842 controls from 23 studies in the Breast Cancer Association Consortium.

Results: Combining the data from all five SNPs, the odds ratio (OR) was 1.05 for being a heterozygote for any of the SNPs and 1.51 for being a rare homozygote for any of the SNPs with an overall trend OR of 1.06 (Ptrend = 0.04). The trend OR among bilateral and familial cases was 1.12 (95% confidence interval, 1.02-1.23; Ptrend = 0.02).

Conclusions: In this large combined analysis, these five missense ATM SNPs were associated with a small increased risk of breast cancer, explaining an estimated 0.03% of the excess familial risk of breast cancer.

Impact: Testing the combined effects of rare missense variants in known breast cancer genes in large collaborative studies should clarify their overall contribution to breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 19(9); 2143–51. ©2010 AACR.
Genetic Polymorphisms in Adaptive Immunity Genes and Childhood Acute Lymphoblastic Leukemia
Authors: Chang Jeffrey S. , Wiemels Joseph L. , Chokkalingam Anand P. , Metayer Catherine , Barcellos Lisa F. , Hansen Helen M. , Aldrich Melinda C. , Guha Neela , Urayama Kevin Y. , Scélo Ghislaine , Green Janet , May Suzanne L. , Kiley Vincent A. , Wiencke John K. , Buffler Patricia A.
Published: September 2010

Background: Childhood acute lymphoblastic leukemia (ALL) has been hypothesized to have an infection- and immune-related etiology. The lack of immune priming in early childhood may result in abnormal immune responses to infections later in life and increase ALL risk.

Methods: The current analyses examined the association between childhood ALL and 208 single-nucleotide polymorphisms (SNP) of 29 adaptive immune function genes among 377 ALL cases and 448 healthy controls. Single SNPs were analyzed with a log-additive approach using logistic regression models adjusted for sex, age, Hispanic ethnicity, and race. Sliding window haplotype analyses were done with haplotypes consisting of 2 to 6 SNPs.

Results: Of the 208 SNPs, only rs583911 of IL12A, which encodes a critical modulator of T-cell development, remained significant after accounting for multiple testing (odds ratio for each copy of the variant G allele, 1.52; 95% confidence interval, 1.25-1.85; P = 2.9 × 10−5). This increased risk was stronger among firstborn children of all ethnicities and among non-Hispanic children with less day care attendance, consistent with the hypothesis about the role of early immune modulation in the development of childhood ALL. Haplotype analyses identified additional regions of CD28, FCGR2, GATA3, IL2RA, STAT4, and STAT6 associated with childhood ALL.

Conclusion: Polymorphisms of genes on the adaptive immunity pathway are associated with childhood ALL risk.

Impact: Results of this study support an immune-related etiology of childhood ALL. Further confirmation is required to detect functional variants in the significant genomic regions identified in this study, in particular for IL12A. Cancer Epidemiol Biomarkers Prev; 19(9); 2152–63. ©2010 AACR.
Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 Molar Ratio and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Douglas Jason B. , Silverman Debra T. , Pollak Michael N. , Tao Yuzhen , Soliman Amr S. , Stolzenberg-Solomon Rachael Z.
Published: September 2010

Background: Experimental evidence suggests that an overexpression of insulin-like growth factor (IGF)-I is implicated in human pancreatic tumors. Increased IGF-II and decreased IGF binding protein (IGFBP)-3 serum concentrations have been linked to a number of other cancers.

Methods: We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic circulating IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio concentrations were associated with exocrine pancreatic cancer risk. Between 1994 and 2006, 187 incident cases of pancreatic adenocarcinoma occurred (follow-up of up to 11.7 years). Two controls (n = 374), who were alive at the time the case was diagnosed, were selected for each case and matched by age, race, sex, and date of blood draw. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) with the use of conditional logistic regression, adjusting for smoking.

Results: IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly associated with pancreatic cancer (highest compared with lowest quartile: OR, 1.58; 95% CI, 0.91-2.76; and P-trend = 0.25; OR, 0.86; 95% CI, 0.49-1.50; and P-trend = 0.31; and OR, 0.88; 95% CI, 0.51-1.51; and P-trend = 0.47, respectively). However, a significant positive trend was observed with high IGF-I/IGFBP-3 molar ratio levels (highest compared with lowest quartile: OR, 1.54; 95% CI, 0.89-2.66; P-trend = 0.04).

Conclusion: A higher IGF-I/IGFBP-3 molar ratio represents increased free IGF-I, which may be a risk factor for pancreatic cancer.

Impact: Our results highlight the importance of this biomarker for further investigation in large prospective cohort studies and pooled analysis with other prospective cohorts. Cancer Epidemiol Biomarkers Prev; 19(9); 2298–306. ©2010 AACR.
Selenium and Bladder Cancer Risk: a Meta-analysis
Authors: Amaral André F.S. , Cantor Kenneth P. , Silverman Debra T. , Malats Núria
Published: September 2010

Background: Selenium is considered to be an antioxidant, and its high levels have been inversely associated with cancer risk of several sites. This meta-analysis examined the relationship between levels of selenium measured in serum and toenails, and the risk of bladder cancer.

Methods: A meta-analysis using data from seven published epidemiologic studies (three case-control, three nested case-control, one case-cohort) published before March 2010 was done to examine the association between levels of selenium and bladder cancer. Fixed and random effects analyses were done to calculate meta-odds ratio (mOR) and 95% confidence intervals (CI). Heterogeneity among studies was measured by the I2 statistic.

Results: Overall, the risk of bladder cancer was inversely associated with elevated levels of selenium according to a random-effects model (mOR = 0.61; 95% CI, 0.42-0.87). The mORs were 0.95 (95% CI, 0.69-1.27) and 0.55 (95% CI, 0.32-0.95) among men and women, respectively. Sex, type of sample specimen, smoking status, and study design were found to be potential sources of heterogeneity.

Conclusions: A significant protective effect of selenium, observed mainly among women, may result from gender-specific differences in its accumulation and excretion. The heterogeneity found among studies was mainly linked to the different biological sample specimens used to measure the selenium concentrations and the small size of the studies. Although these results suggest a protective effect of selenium for bladder cancer risk, additional large studies are warranted to support these preliminary evidence.

Impact: The present results suggest a beneficial effect of high selenium intake for bladder cancer risk. Cancer Epidemiol Biomarkers Prev; 19(9); 2407–15. ©2010 AACR.
“Contextual” Synthetic Lethality and/or Loss of Heterozygosity: Tumor Hypoxia and Modification of DNA Repair
Authors: Chan Norman , Bristow Robert G.
Published: September 2010

Hypoxia exists in every solid tumor and is associated with poor prognosis because of both local and systemic therapeutic resistance. Recent studies have focused on the interaction between tumor cell genetics and the dynamic state of oxygenation and metabolism. Hypoxia generates aggressive tumor cell phenotypes in part owing to ongoing genetic instability and a “mutator” phenotype. The latter may be due to suppression of DNA mismatch repair (MMR), nucleotide excision repair (NER), and double-strand break (DSB) repair. We propose a theoretical model in which hypoxia-mediated defects in DNA repair can lead to “contextual loss of heterozygosity” and drive oncogenesis. Additionally, hypoxia-mediated repair defects can be specifically targeted by DNA damaging agents and/or “contextual synthetic lethality” to kill repair-deficient cells and preserve the therapeutic ratio. These proposed concepts support the interrogation of solid tumors to document repair defects in both oxic and hypoxic tumor subregions as a conduit to novel clinical trials within the context of personalized medicine. Clin Cancer Res; 16(18); 4553–60. ©2010 AACR.
Multicenter Cluster-Randomized Trial of a Multifactorial Intervention to Improve Antihypertensive Medication Adherence and Blood Pressure Control Among Patients at High Cardiovascular Risk (The COM99 Study)
Authors: Pladevall Manel , Brotons Carlos , Gabriel Rafael , Arnau Anna , Suarez Carmen , de la Figuera Mariano , Marquez Emilio , Coca Antonio , Sobrino Javier , Divine George , Heisler Michele , Williams L. Keoki ,   Writing Committee on behalf of the COM99 Study Group*
Published: September 2010

Background—

Medication nonadherence is common and results in preventable disease complications. This study assessed the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events.

Methods and Results—

In this multicenter, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients' pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end point of all-cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62, 95% confidence interval 0.50 to 0.78) and were more likely to be adherent (odds ratio 1.91, 95% confidence interval 1.19 to 3.05) than control group patients at 6 months. After 5 years, 16% of the patients in the intervention group and 19% in the control group met the composite end point (hazard ratio 0.97, 95% confidence interval 0.67 to 1.39).

Conclusions—

A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN35208258.
Culture and Disability: Advancing Comparative Research
Authors: Meyer Heinz-Dieter
Published: September 2010

Cultures differ greatly as to which specific conditions they recognize as a disability, how they interpret matters of causation and consequence, and which kinds of remedy they believe adequate. The papers in this special issue of Comparative Sociology explore the institutional and cultural variation of disability as well as the underlying causes, including a culture’s degree of individualism / collectivism.
Is Family-friendly Management Good for Firms? The Diffusion and Performance of Family-friendly Workplaces in South Korea
Authors: Lee Byoung-Hoon , Kim Jong-Sung
Published: September 2010

Using the Korea Workplace Panel Survey data, this study examines the extent of diffusion of family-friendly programmes in Korean workplaces and the effect the programmes have on organizational performance, including employee turnover, labour productivity, and labour—management relations, under the presence and moderation of high performance work systems (HPWS) practices. The diffusion of family-friendly management in Korean firms has been very limited in comparison with British workplaces, despite the Korean government’s policy efforts to promote greater work—family balance. Our analysis reveals that family-friendly programmes do not always benefit firms. Dependent care programmes are beneficial for organizational performance to a certain degree, whereas flexible work schedules are not effective in reducing turnover, exhibiting a negative effect on labour productivity. However, flextime practice in Korea differs to a certain extent from western countries, where employees are allowed to flexibly alter their working schedules to promote work—family integration. Furthermore, family-friendly programmes in Korea do not complement HPWS practices in the enhancement of organizational performance.
Determinants of Employer-sponsored Training Participation for Young Workers during Economic Downturns: Evidence from the Past
Authors: Watanabe Satoshi P.
Published: September 2010

This study is devoted to learning from the past and understanding the determinants of training participation for young workers during recessionary periods. Evidence is found that the post-training wage growth expected over a few years after training, rather than an immediate wage gain upon completion of training, was a significant motive for young individuals to invest in training in the midst of the post-Black Monday recession. An immediate wage gain due to training, in contrast, provides no statistically significant evidence. These results indicate that young workers’ decision to invest in skill acquisition was made reasonably based on a stretched span of wage profile even during the period of economic slowdown rather than based on a myopic view as is often believed to be typical behaviour of young individuals. An important implication of this study is that the human capital of young workers continues to accumulate even in recessionary periods if an employer plans workers’ career development and earnings growth potentials beyond the time of economic hardship.
The Polaroid Image as Photo-Object
Authors: Buse Peter
Published: September 2010

This article is part of a larger project on the cultural history of Polaroid photography and draws on research done at the Polaroid Corporate archive at Harvard and at the Polaroid company itself. It identifies two cultural practices engendered by Polaroid photography, which, at the point of its extinction, has briefly flared into visibility again. It argues that these practices are mistaken as novel but are in fact rediscoveries of practices that stretch back as many as five decades. The first section identifies Polaroid image-making as a photographic equivalent of what Tom Gunning calls the ‘cinema of attractions’. That is, the emphasis in its use is on the display of photographic technologies rather than the resultant image. Equally, the common practice, in both fine art and vernacular circles, of making composite pictures with Polaroid prints, draws attention from image content and redirects it to the photo as object.
Wonder, Magic and the Fantastical Margins: Medieval Visual Culture and Cinematic Special Effects
Authors: Griffiths Alison
Published: September 2010

What are the nature and power of special effects that induce such strong reactions in cinema spectators, and is it possible to find an analog to this contemporary fascination in the visual culture of the Middle Ages? This article contends that spectators during the medieval period may have responded to fantastical, supernatural, phantasmagorical, miraculous, satanic, or spectacular images with a similar sense of awe and wonder as contemporary viewers of cinematic special effects. Proposing a reconsideration of the pre-history of cinematic special effects, the author suggests that the allure of cinematic special effects is broader than the historical experience of cinema, and that image-makers were exploiting the embodied modes of viewing offered by special effects far earlier than the invention of motion pictures.
A Vinyl Platform for Dissent: Designer Toys and Character Merchandising
Authors: Steinberg Marc
Published: September 2010

‘Designer toys’ or ‘urban vinyl’ offer themselves as a fascinating site of resistance to the contemporary circulation of images and things. This article provides an introduction to the field of designer toys and argues that the field may be understood to be a materially situated critique of the commercial practice of character merchandising. Beginning with a description of the logic of character merchandising, this article goes on to demonstrate how designer toys critically and creatively transform some of the fundamental tenets of this practice, advancing a critique of character merchandising via the material objects themselves. In this age of image circulation, the case of the designer toy demonstrates how material artefacts can themselves become significant sites of critique.