bluuebunny/crossref_metadata_2025 huggingface dataset:
Immediate Product after Exposing Si(111)-7×7 Surface to O2 at 300 K
Authors: Yoshigoe Akitaka , Teraoka Yuden
Published: November 2010

Using real-time O 1s X-ray photoelectron spectroscopy together with Si 2p X-ray photoelectron spectroscopy, the oxygen bonding configurations of oxides shortly after exposing the Si(111)-7×7 surface to O2 at 300 K are revealed. It is found that the ins structure firstly forms where one oxygen atom sits in the backbond of the silicon adatom. It is confirmed that the chemisorbed molecular oxygen, the so-called paul oxygen, is the adsorbate on top of the ins structure. It is also clarified that the ad–ins structure and the ins–tri structure, where ad means an oxygen atom adsorbed onto top of the silicon adatom and tri means the interstitial oxygen atom, appear after a short time. The results implying the presence of mobile O2 on the surface were obtained.
A New High-Performance Ion Source Based on Magnetically Neutral Loop Discharge
Authors: Shimokawa Fusao
Published: November 2010

We have developed a new high-performance ion source on the basis of the high-density plasma formation method known as magnetically neutral loop discharge (NLD). The ion source consists of three separate electromagnetic coils, an ion extraction electrode, and a quartz vessel plasma chamber with a one-turn RF antenna coil, which is the main component of conventional RF ion sources. The three electromagnetic coils are located around the periphery of the plasma chamber. The current in the middle coil flows opposite to the currents in the top and bottom coils. With this configuration, our source produces a high plasma density of 1011cm-3, which is about ten times higher than that of a conventional source under a low gas pressure of 0.1 Pa. In addition, it is possible to control both the ring like plasma diameter and the high-density plasma generation position in the plasma chamber. As a result, we achieved a high ion current density of up to 1 mA/cm2at 50 V of ion extraction voltage, which is almost five times higher than the conventional source. Furthermore, we also obtained a high ion current uniformity of ±5% over a 6-in.-diameter wafer using the source's plasma space controllability. A processing system that uses this ion source will contribute to faster processing, high-quality processing, and excellent-uniformity processing for ion beam etching, ion beam deposition, and ion beam sputter deposition. Many other applications are also expected.
Temperature Analysis of Laser Gain Plasma Medium in a Slab-Type RF Discharge Excited CO2 Laser Using Near Infrared Diode-Laser Absorption Spectroscopy
Authors: Yasuda Takashi , Nozue Hirokazu , Fujishiro Takehiko , Tei Kazuyoku , Yamaguchi Shigeru
Published: November 2010

A novel optical method of temperature measurement was used to analyze a slab-type 40 MHz RF discharge excited CO2 laser plasma active medium. The method was based on near-infrared absorption spectroscopy with a 1.6 µm distributed-feedback (DFB) semiconductor laser. Gas temperatures from 450 to 650 K were measured at pressures of 1 to 6 kPa with discharge electrode distances of 5.0 and 7.5 mm. This method may provide a practical sensor for the real-time diagnostics of the active medium of CO2 lasers.
New Radiophotoluminescence Glass Dosimeter with Specialized Radiation-Sensitive Surface Layer
Authors: Maki Daisuke , Kobayashi Hatsumi , Sato Fuminobu , Murata Isao , Kato Yushi , Yamamoto Takayoshi , Iida Toshiyuki
Published: November 2010

A new radiophotoluminescence (RPL) dosimeter with a specialized radiation-sensitive surface layer was successfully fabricated from phosphate glass by the melting method. The radiation-sensitive surface layer, which was measured using an excitation laser and a fluorescence microscope, was formed through the thermal diffusion of silver atoms. It was found from RPL observations that the diffusion coefficient of silver atoms in phosphate glass was about 1.4 µm2/s at 400 °C and activation energy for silver atoms was about 0.7 eV. It was also confirmed that the newly synthesized dosimeter showed a satisfactory response to alpha rays and the effect of the annealing process on the dosimeter could be estimated on the basis of a thermal diffusion model of silver atoms in the glass.
Stimulated Superradiance Emitted from Periodic Microbunches of Electrons
Authors: Seo Yoonho , Lee Wonhyung
Published: November 2010

Electron bunches of a picosecond scale can emit terahertz waves superradiantly. Superradiant undulator radiation is considered for a train of periodic bunches injected into a resonating cavity. It is found that the cavity modes excited by successive bunches can be accumulated when they satisfy the accumulation condition, [Δω
n
/2π+(n + 2L/λ
w
)/T
R] T
b = integer, where Δω
n
is the frequency mismatch, n is the mode number, L is the cavity length, λ
w
is the undulator period, T
R is the round trip time, and T
b is the bunch period. Numerical simulation shows growth of resonant modes (Δω
n
=0) and specific off-resonant modes (Δω
n
=2πp/T
R, p=odd) when the accumulation condition is fulfilled. Also identified in simulation is stimulation of superradiant emission in the radiation pulses excited through grazing resonance. The radiative efficiency is observed to increase bunch after bunch until saturation is reached.
Complementary Metal–Oxide–Semiconductor Micro-Electro-Mechanical-System Reconfigurable Cantilever Resonator with Multiple Electrostatic Electrodes
Authors: Shieh Li-Jung , Chiou Jin-Chern
Published: November 2010

In this paper, we present a prestress vertical comb drive resonator with a frequency tuning capability. The resonator consists of three sets of comb fingers, which act as driving electrodes. The comb fingers are fabricated along with a composite beam. One end of the composite beam is clamped to the anchor, whereas the other end is elevated vertically by the residual stress. A clamped force, which is formed by a DC voltage, is utilized to restrain the vibration of the composite beam. By applying a DC clamped voltage and a driving voltage in different electrodes, the resonator exhibits different frequency responses. The device is fabricated through a 0.35 µm complementary metal–oxide–semiconductor (CMOS) process with a post-CMOS micromachining process. Experimental results indicate that the initial resonant frequency of the device is 18.6 kHz, and the maximum frequency tuning range up to 28.5% is obtained. The resonator device can recover its original frequency without causing any structural damage.
Surface Modification of SiO2 Microchannels with Biocompatible Polymer Using Supercritical Carbon Dioxide
Authors: Saito Tatsuro , Momose Takeshi , Hoshi Toru , Takai Madoka , Ishihara Kazuhiko , Shimogaki Yukihiro
Published: November 2010

The surface of 500-mm-long microchannels in SiO2 microchips was modified using supercritical CO2 (scCO2) and a biocompatible polymer was coated on it to confer biocompatibility to the SiO2 surface. In this method, the SiO2 surface of a microchannel was coated with poly(ethylene glycol monomethacrylate) (PEGMA) as the biocompatible polymer using allyltriethoxysilane (ATES) as the anchor material in scCO2 as the reactive medium. Results were compared with those using the conventional wet method. The surface of a microchannel could not be modified by the wet method owing to the surface tension and viscosity of the liquid, but it was modified uniformly by the scCO2 method probably owing to the near-zero surface tension, low viscosity, and high diffusivity of scCO2. The effect of the surface modification by the scCO2 method to prevent the adsorption of protein was as high as that of the modification by the wet method. Modified microchips can be used in biochemical and medical analyses.
Formation of Selective High Barrier Region by Inductively Coupled Plasma Treatment on GaN-Based Light-Emitting Diodes
Authors: Kuo Ting-Wei , Lin Shi-Xiong , Hung Pin-Kun , Chong Kwok-Keung , Hung Chen-I , Houng Mau-Phon
Published: November 2010

By inductively coupled plasma (ICP) etching, a selective high barrier region (SHBR) was fabricated below the p-pad metal electrode for modifying the injection current distribution on p-type GaN of GaN-based light-emitting diodes (LEDs). Through the analysis of current noise power spectra, the samples with ICP etching treatment have excess nitrogen vacancies at the selectively etched surface of p-type GaN; thus, they have a lower hole concentration than the as-grown sample, resulting in a larger barrier height for carrier transport. With this SHBR, the light-output power for the LED chip measured at 20 mA was significantly increased by 12% as compared with that for the conventional LED chip. The light-output power increase could be attributed to a relative reduction in optical power absorption under the p-pad electrode and a higher density of current effectively injected into the active layer of the LED by the SHBR structure.
Resist Parameter Extraction from Line-and-Space Patterns of Chemically Amplified Resist for Extreme Ultraviolet Lithography
Authors: Kozawa Takahiro , Oizumi Hiroaki , Itani Toshiro , Tagawa Seiichi
Published: November 2010

The development of extreme ultraviolet (EUV) lithography has progressed owing to worldwide effort. As the development status of EUV lithography approaches the requirements for the high-volume production of semiconductor devices with a minimum line width of 22 nm, the extraction of resist parameters becomes increasingly important from the viewpoints of the accurate evaluation of resist materials for resist screening and the accurate process simulation for process and mask designs. In this study, we demonstrated that resist parameters (namely, quencher concentration, acid diffusion constant, proportionality constant of line edge roughness, and dissolution point) can be extracted from the scanning electron microscopy (SEM) images of patterned resists without the knowledge on the details of resist contents using two types of latest EUV resist.
Characterization of Plasma-Induced Damage of Selectively Recessed GaN/InAlN/AlN/GaN Heterostructures Using SiCl4and SF6
Authors: Ostermaier Clemens , Pozzovivo Gianmauro , Basnar Bernhard , Schrenk Werner , Carlin Jean-François , Gonschorek Marcus , Grandjean Nicolas , Vincze Andrej , Tóth Lajos , Pécz Bela , Strasser Gottfried , Pogany Dionyz , Kuzmik Jan
Published: November 2010

We have investigated an inductively coupled plasma etching recipe using SiCl4and SF6with a resulting selectivity >10 for GaN in respect to InAlN. The formation of an etch-resistant layer of AlF3on InAlN required about 1 min and was noticed by a 4-times-higher initial etch rate on bare InAlN barrier high electron mobility transistors (HEMTs). Comparing devices with and without plasma-treatment below the gate showed no degradation in drain current and gate leakage current for plasma exposure durations shorter than 30 s, indicating no plasma-induced damage of the InAlN barrier. Devices etched longer than the required time for the formation of the etch-resistant barrier exhibited a slight decrease in drain current and an increase in gate leakage current which saturated for longer etching-time durations. Finally, we could prove the quality of the recipe by recessing the highly doped 6 nm GaN cap layer of a GaN/InAlN/AlN/GaN heterostructure down to the 2 nm thin InAlN/AlN barrier layer.
Data Analysis of X-ray Fluorescence Holography by Subtracting Normal Component from Inverse Hologram
Authors: Happo Naohisa , Hayashi Kouichi , Hosokawa Shinya
Published: November 2010

X-ray fluorescence holography (XFH) is a powerful technique for determining three-dimensional local atomic arrangements around a specific fluorescing element. However, the raw experimental hologram is predominantly a mixed hologram, i.e., a mixture of hologram generated in both normal and inverse modes, which produces unreliable atomic images. In this paper, we propose a practical subtraction method of the normal component from the inverse XFH data by a Fourier transform for the calculated hologram of a model ZnTe cluster. Many spots originating from the normal components could be properly removed using a mask function, and clear atomic images were reconstructed at adequate positions of the model cluster. This method was successtully applied to the analysis of experimental ZnTe single crystal XFH data.
Long-Range Testing of Welded Elbow Pipe Using the T(0,1) Mode Ultrasonic Guided Wave
Authors: Nishino Hideo , Masuda Shuichi , Mizobuchi Yuki , Asano Tadashi , Yoshida Kenichi
Published: November 2010

An experimental investigation of sensitivity in defect detection in welded elbow pipes using the T(0, 1) mode guided wave was carried out. A piezoelectric ring-shaped sensor system was cramped on one of the two straight parts in the straight-elbow-straight setting. An artificial defect was introduced into the other straight part. To evaluate the sensitivities, the depth of the artificial defect was gradually increased to 2.0 mm by 0.05 mm increments. The following are the obtained experimental results. (1) Spurious signals due to the two welds, which could be markedly changed by varying the welding conditions were found. (2) These spurious signals interfered with and masked the defect signal, but changes in signal amplitude owing to the incremental defect could be sufficiently detected. (3) Sensitivities of defect detection in welded elbow pipes were approximately 1/4–1/5 that in a straight pipe. At the end of the paper, the characteristics of the observed waveform in the welded elbow pipes are discussed for use in the guided wave inspection.
Development of Near-Field Microwave Microscope with the Functionality of Scanning Tunneling Spectroscopy
Authors: Machida Tadashi , Gaifullin Marat B. , Ooi Shuuich , Kato Takuya , Sakata Hideaki , Hirata Kazuto
Published: November 2010

We describe the details of an original near-field scanning microwave microscope, developed for simultaneous measurements of local density-of-states (LDOS) and local ohmic losses (LOL). Improving microwave detection systems, we have succeeded in distinguishing the LDOS and LOL even between two low resistance materials; gold and highly orientated pyrolitic graphite. The experimental data indicate that our microscope holds a capability to investigate both LDOS and LOL in nanoscale.
Fabrication of Ultralow-Loss Tapered Optical Fibers and Microtoroidal Resonators
Authors: Aoki Takao
Published: November 2010

We report simple, reproducible methods of fabricating tapered optical fibers with subwavelength diameter and silica microtoroidal resonators, both operating at a wavelength of 850 nm. The transmission loss of tapered fibers was reduced to 0.03 dB by controlling the adiabaticity of the tapered region. The Q factor of 3 ×108 was obtained for a toroidal microresonator with 40 µm diameter.
Improvement of Negative Lens Property of Liquid Crystal Device
Authors: Kawamura Marenori , Goto Hisashi , Yumoto Eigi
Published: November 2010

A liquid crystal (LC) device with double circularly hole-patterned electrodes and an external flat electrode is developed to improve the range of negative lens power. The negative lens power can be improved by applying the voltage to the additional new hole-patterned electrode. The lens power of the LC device with the double circularly hole-patterned electrodes is about threefold as large as that of the conventional LC device with a single hole-patterned electrode.
Teaching acid/base physiology in the laboratory
Authors: Friis Ulla G. , Plovsing Ronni , Hansen Klaus , Laursen Bent G. , Wallstedt Birgitta
Published: November 2010

Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory exercise in acid/base physiology that would provide students with unambiguous and reproducible data that clearly would illustrate the theory in practice. The laboratory exercise was developed to include both metabolic acidosis and respiratory alkalosis. Data were collected from 56 groups of medical students that had participated in this laboratory exercise. The acquired data showed very consistent and solid findings after the development of both metabolic acidosis and respiratory alkalosis. All results were consistent with the appropriate diagnosis of the acid/base disorder. Not one single group failed to obtain data that were compatible with the diagnosis; it was only the degree of acidosis/alkalosis and compensation that varied.
Fishbone-Associated Actinomycosis of the Anterior Cervical Space: A Diagnostic Dilemma
Authors: Lee Sang Kwon , Kim Mi Jeong , Kwon Sun Young
Published: November 2010

We report the imaging and pathologic findings of fishbone-associated actinomycosis of the anterior cervical space in a 57-year-old man, misdiagnosed preoperatively as a malignancy originating from thyroglossal duct cyst. CT revealed an enhancing mass containing a small abscess pocket and two sharp linear calcifications within it, which infiltrated into the strap muscle. Pathologic examination demonstrated two fishbones within the actinomycotic abscess. Fishbone-associated actinomycosis should be considered when a cervical mass contains sharp linear calcifications.
Herniation of the Anterior Wall of the Stomach into a Congenital Postdiaphragmatic Space: An Unusual Complication following Laparoscopic Nissen Fundoplication
Authors: Eisawi A. , Al-Temimi A. , Dirie Mohamed , Bukhari S. , Siddiqui M.
Published: November 2010

Postoperative herniation of the stomach into potential spaces is a rare but serious complication of Nissen fundoplication. We report a 55-year-old female who presented with persistent vomiting shortly following laparoscopic Nissen fundoplication. At laparotomy, the anterior wall of the stomach was noted to be herniating into a congenital space behind the diaphragm. Anterior gastropexy was performed following the reduction of the herniating gastric segment. A high index of suspicion followed by aggressive and timely intervention is necessary to diagnose and manage postoperative gastric herniation and reduce the subsequent morbidity and mortality.
Physical Activity and Obesity: Biomechanical and Physiological Key Concepts
Authors: Nantel Julie , Mathieu Marie-Eve , Prince François
Published: November 2010

Overweight (OW) and obesity (OB) are often associated with low levels of physical activity. Physical activity is recommended to reduce excess body weight, prevent body weight regain, and decrease the subsequent risks of developing metabolic and orthopedic conditions. However, the impact of OW and OB on motor function and daily living activities must be taken into account. OW and OB are associated with musculoskeletal structure changes, decreased mobility, modification of the gait pattern, and changes in the absolute and relative energy expenditures for a given activity. While changes in the gait pattern have been reported at the ankle, knee, and hip, modifications at the knee level might be the most challenging for articular integrity. This review of the literature combines concepts and aims to provide insights into the prescription of physical activity for this population. Topics covered include the repercussions of OW and OB on biomechanical and physiological responses associated with the musculoskeletal system and daily physical activity. Special attention is given to the effect of OW and OB in youth during postural (standing) and various locomotor (walking, running, and cycling) activities.
Bevacizumab plus Irinotecan-Based Regimens in the Treatment of Metastatic Colorectal Cancer
Authors: Heinemann Volker , Hoff Paulo M.
Published: November 2010

Objectives: Bevacizumab is a monoclonal antibody that directly inhibits vascular endothelial growth factor, a key regulator of angiogenesis. Bevacizumab significantly improves progression-free and/or overall survival in metastatic colorectal cancer in combination with standard chemotherapy. This review describes the evolution of irinotecan-based regimens for metastatic colorectal cancer and evaluates the addition of bevacizumab to these regimens. Methods: Literature searches from large publication databases (PubMed, ASCO, ASCO GI, ESMO) were performed to capture key data relevant to bevacizumab, irinotecan, and the treatment of colorectal cancer. Results: Data from numerous large, multinational studies support the addition of bevacizumab to irinotecan-containing chemotherapy regimens for further improvement in patient outcomes. In a randomized, placebo-controlled trial, addition of bevacizumab to irinotecan significantly improved progression-free survival, overall survival and response rate in patients with metastatic colorectal cancer, and these results are supported by a number of other clinical trials and observational studies. Furthermore, the addition of bevacizumab to irinotecan improves outcomes regardless of K-ras mutational status. Bevacizumab has a well-established safety profile and the toxicities associated with its use are usually mild in severity and easily manageable. Conclusions: Addition of bevacizumab to irinotecan-containing regimens is an effective therapy option for the treatment of metastatic colorectal cancer.
Variants of the Adenosine A2A Receptor Gene Are Protective against Proliferative Diabetic Retinopathy in Patients with Type 1 Diabetes
Authors: Charles Bashira A. , Conley Yvette P. , Chen Guanjie , Miller Rachel G. , Dorman Janice S. , Gorin Michael B. , Ferrell Robert E. , Sereika Susan M. , Rotimi Charles N. , Orchard Trevor J.
Published: November 2010

Aims: The adenosine A2A receptor (ADORA2A) may ameliorate deleterious physiologic effects associated with tissue injury in individuals with diabetes. We explored associations between variants of the ADORA2A gene and proliferative diabetic retinopathy (PDR) in a cohort of patients with type 1 diabetes (T1D). Methods: The participants were from the Pittsburgh Epidemiology of Diabetes Complications prospective study of childhood-onset T1D. Stereoscopic photographs of the retinal fundus taken at baseline, then biennially, for 10 years were used to define PDR according to the modified Airlie House system. Two tagging single nucleotide polymorphisms (tSNPs; rs2236624-C/T and rs4822489-G/T) in the ADORA2A gene were selected using the HapMap (haplotype map) reference database. Results: A significant association was observed between SNP rs2236624 and PDR in the recessive genetic model. Participants homozygous for the T allele displayed a decreased risk of developing prevalent PDR (odds ratio, OR = 0.36; p = 0.04) and incident PDR (hazard ratio = 0.156; p = 0.009), and for all cases of PDR combined (OR = 0.23; p = 0.001). The protective effect of T allele homozygosity remained after adjusting for covariates. Similarly, for SNP rs4822489, an association between PDR and T allele homozygosity was observed following covariate adjustment (OR = 0.55; 95% CI: 0.31–0.92; p = 0.04). Conclusion: Genetic variants of ADORA2A offer statistically significant protection against PDR development in patients with T1D.
A Single-Arm Phase II Trial of First-Line Paclitaxel in Combination with Lapatinib in HER2-Overexpressing Metastatic Breast Cancer
Authors: Jagiello-Gruszfeld Agnieszka , Tjulandin Sergei , Dobrovolskaya Natalya , Manikhas Alexey , Pienkowski Tadeusz , DeSilvio Michelle , Ridderheim Mona , Abbey Rowena
Published: November 2010

Introduction: Lapatinib, an orally active tyrosine kinase inhibitor of epidermal growth factor receptor ErbB1 (EGFR) and ErbB2 (HER2), has activity as monotherapy and in combination with chemotherapy in HER2-overexpressing metastatic breast cancer (MBC). Methods: This phase II single-arm trial assessed the safety and efficacy of first-line lapatinib in combination with paclitaxel in previously untreated patients with HER2-overexpressing MBC. The primary endpoint was the overall response rate (ORR). Secondary endpoints were the duration of response (DoR), time to response, time to progression, progression-free survival (PFS), overall survival, and the incidence and severity of adverse events. All endpoints were investigator- and independent review committee (IRC)-assessed. Results: The IRC-assessed ORR was 51% (29/57 patients with complete or partial response) while the investigator-assessed ORR was 77% (44/57). As per the IRC, the median DoR was 39.7 weeks, and the median PFS was 47.9 weeks. The most common toxicities were diarrhea (56%), neutropenia (44%), rash (40%), fatigue (25%), and peripheral sensory neuropathy (25%). Conclusions: First-line lapatinib plus paclitaxel for HER2-overexpressing MBC produced an encouraging ORR with manageable toxicities. This combination may be useful in first-line treatment for patients with HER2-overexpressing MBC and supports the ongoing evaluation of this combination as first-line therapy in HER2-overexpressing MBC.
Perspectives in Microvascular Fluid Handling: Does the Distribution of Coagulation Factors in Human Myocardium Comply with Plasma Extravasation in Venular Coronary Segments?
Authors: Jacob Matthias , Chappell Daniel , Stoeckelhuber Mechthild , Welsch Ulrich , Rehm Markus , Bruegger Dirk , Kaczmarek Ingo , Conzen Peter , Becker Bernhard F.
Published: November 2010

Background: Heterogeneity of vascular permeability has been suggested for the coronary system. Whereas arteriolar and capillary segments are tight, plasma proteins pass readily into the interstitial space at venular sites. Fittingly, lymphatic fluid is able to coagulate. However, heart tissue contains high concentrations of tissue factor, presumably enabling bleeding to be stopped immediately in this vital organ. The distribution of pro- and anti-coagulatively active factors in human heart tissue has now been determined in relation to the types of microvessels. Methods and Results: Samples of healthy explanted hearts and dilated cardiomyopathic hearts were immunohistochemically stained. Albumin was found throughout the interstitial space. Tissue factor was packed tightly around arterioles and capillaries, whereas the tissue surrounding venules and small veins was practically free of this starter of coagulation. Thrombomodulin was present at the luminal surface of all vessel segments and especially at venular endothelial cell junctions. Its product, the anticoagulant protein C, appeared only at discrete extravascular sites, mainly next to capillaries. These distribution patterns were basically identical in the healthy and diseased hearts, suggesting a general principle. Conclusions: Venular extravasation of plasma proteins probably would not bring prothrombin into intimate contact with tissue factor, avoiding interstitial coagulation in the absence of injury. Generation of activated protein C via thrombomodulin is favored in the vicinity of venular gaps, should thrombin occur inside coronary vessels. This regionalization of distribution supports the proposed physiological heterogeneity of the vascular barrier and complies with the passage of plasma proteins into the lymphatic system of the heart.
Survival in Congenital Diaphragmatic Hernia: Use of Predictive Equations in the ECMO Population
Authors: Hoffman Suma B. , Massaro An N. , Gingalewski Cynthia , Short Billie Lou
Published: November 2010

Background: Equations have been proposed by the Wilford Hall/Santa Rosa (WHSR) and Congenital Diaphragmatic Hernia Study Group (CDHSG) for predicting survival in patients with CDH. The CDHSG stratifies risk based on a logistic regression equation incorporating birth weight and 5-min Apgar score, while the WHSR group uses the difference between maximum pO2 and maximum pCO2 as an index of risk. These models have not been applied specifically to the CDH ECMO (extracorporeal membrane oxygenation) population, a group at highest mortality risk. Objectives: To evaluate the WHSR and CDHSG predictive equations when applied to a population of patients with CDH requiring ECMO life support. Methods: A single-center retrospective review was conducted on infants with CDH treated with ECMO between 1993 and 2007. Predicted and actual outcomes were compared using receiver operating curve (ROC) analyses in which an area under the curve (AUC) of 1 denotes 100% agreement between predicted and actual outcomes. Kaplan-Meier analyses were also used to compare survival of patients who were risk-categorized according to each prediction model. Minimum pre-ECMO pCO2 was likewise evaluated as a predictor of survival. Results: Overall survival was 50% in 62 CDH patients treated with ECMO during the study period. The CDHSG equation did not discriminate between survivors and nonsurvivors (AUC 0.55, p = 0.499). The modified WHSR formula showed better discrimination of survival (AUC 0.71, p = 0.004). Lowest achievable pre-ECMO pCO2 had the highest AUC (0.723, p = 0.003). Patients with minimum pre-ECMO pCO2 <50 mm Hg had 56% survival, while those with >70 mm Hg had 0% survival. Conclusions: Equations proposed to predict survival in CDH patients may not discriminate survivors from nonsurvivors in the ECMO population. In this highest risk group, factors such as birth weight and Apgar score are less critical in estimating mortality risk than indicators of ventilation and oxygenation that reflect the degree of pulmonary hypoplasia.
Chronic Inflammation, Colorectal Cancer and Gene Polymorphisms
Authors: Boland C. Richard
Published: November 2010

Chronic inflammation is commonly present in gastrointestinal mucosal sites at increased risk for cancer, such as in inflammatory bowel disease (IBD) or chronic gastritis caused by Helicobacter pylori infection. Why some patients have more mucosal inflammation than others, and why certain individuals with chronic inflammation develop cancer, are problems that have not been solved. Unlike the case for the syndromic forms of familial colorectal cancer (CRC), the risks for IBD and other forms of chronic inflammation have not been linked to highly penetrant single gene mutations. Single nucleotide polymorphisms (SNP) are variations in DNA sequence that can be linked to any phenotype (cancer, chronic inflammation, etc.) in genome-wide association studies (GWAS). CRC has been linked to several highly penetrant single gene loci, as well as multiple SNP. The propensity to develop IBD has not been linked to single gene mutations in most instances, but has been linked to SNP in the NOD2 locus (which appear to create hypomorphic alleles for this bacterial response gene), the IL23R locus, the autophagy gene ATG16L1 and a wide range of other loci including the Toll-like receptors, JAK2 and STAT3, and perhaps 70 more. At present, the problem in predicting risk for chronic inflammation is that there are many genetic polymorphisms with relatively modest individual effects. Our challenge is to understand how the SNPs that are linked to variations in the inflammatory response interact with one another (i.e. to understand the ‘epistasis’ involved), and to integrate this with the variety of individual environmental exposures. This represents an opportunity for informatics science to help personalize our approach to chronic inflammatory diseases of the gut and identify those at greatest risk for cancer.
Molecular Pathogenesis of Helicobacter pylori Infection: The Role of Bacterial Virulence Factors
Authors: Molnar Bela , Galamb Orsolya , Sipos Ferenc , Leiszter Katalin , Tulassay Zsolt
Published: November 2010

Helicobacter pylori is one of the most common pathogens affecting humankind, infecting approximately 50% of the world’s population. Of those infected, many will develop asymptomatic gastritis, but 10% develop gastric or duodenal ulcers. The clinical outcome of the infection may involve a combination of bacterial factors, host factors and environmental factors. In the process of development of gastritis, ulceration and cancer, several cellular and molecular steps follow each other. Infection, acid survival, adhesion, cytotoxicity, epithelial cell turnover changes, inflammation, regeneration or pathological alteration towards erosions, ulceration, and cancer can be observed on the cellular level. Bacterial factors like urease, AmiE, AmiF, hydrogenase and arginase are needed for survival in the acidic gastric environment. The bacterial flagellae are essential to move the bacteria towards the epithelial surface. Adhesive factors like BabA, SabA and ureaseA are necessary for adhesion against MHC-II complexes and Le antigens. The bacteria VacA and CagA are cytotoxic factors. The Cag type IV secretion system delivers these proteins inside the epithelial cells. After disruption of epithelial cell junctions, the bacteria can pass through the gastric wall facing direct immune response from neutrophils, lymphocytes, mast cells and dendritic cells. This review describes and summarizes our present molecular biological information and knowledge about the Helicobacter infective component, cell functions and processes. The possible role of host counter responses and interactions with gastric epithelia and immune cells are also detailed.
Multimodal Therapy of Gastric Cancer
Authors: Mlkvý Peter
Published: November 2010

Adenocarcinoma of the stomach is the 2nd most common cancer worldwide. The 5-year survival rates after curative surgical resection decline from 60–90% in stage I, to 30–50% in stage II and finally drop to only to 10–25% for patients in stage III of this disease. Surgical treatment is the only therapeutic modality that has a potentially curative effect. According to certain criteria, early gastric cancer limited to the mucosa or submucosa is indicated for endoscopic mucosal resection. In advanced gastric cancer with surgical approach, the questions of type of resection, extent of lymph node dissection and indication for splenectomy do arise. R0 resection represented with macroscopic- and microscopic-free resection margins is the ultimate goal for a surgeon. Chemotherapy is the treatment of choice in stage IV for unresectable disease. According to numerous randomized controlled trials, adjuvant chemotherapy versus chemoradiotherapy have been accepted for stages Ib–IIIb of this disease. Combination chemotherapy seems to be more effective than monotherapy. Neoadjuvant chemotherapy is administered with the aim to downstage a locally advanced tumor prior to attempting curative resection. New therapeutic possibilities include agents like angiogenesis inhibitors, human epidermal growth factor receptor family inhibitors and inhibitors of small molecules (tyrosine kinase inhibitors). Survival rates in resectable gastric cancer are influenced mainly by the depth of invasion through the gastric wall and by the presence or absence of regional lymph node involvement. Positive margins in resected patients are associated with very poor prognosis.
Epidemiology of Pancreatic Cancer: An Update
Authors: Maisonneuve Patrick , Lowenfels Albert B.
Published: November 2010

Pancreatic cancer, although infrequent, has a very poor prognosis, making it one of the 4 or 5 most common causes of cancer mortality in developed countries. Its incidence varies greatly across regions, which suggests that lifestyle factors such as diet, and environmental factors, such as vitamin D exposure, play a role. Because pancreatic cancer is strongly age-dependent, increasing population longevity and ageing will lead to an increase of the global burden of pancreatic cancer in the coming decades. Smoking is the most common known risk factor, causing 20–25% of all pancreatic tumors. Although a common cause of pancreatitis, heavy alcohol intake is associated only with a modest increased risk of pancreatic cancer. While viruses do not represent a major risk factor, people infected with Helicobacter pylori appeared to be at high risk of pancreatic cancer. Many factors associated with the metabolic syndrome, including overweight and obesity, impaired glucose tolerance, and long-standing diabetes also increase the risk disease, while atopic allergy and use of metformin as a treatment for diabetes have been associated with a reduced risk of pancreatic cancer. A family history of pancreatic cancer is associated with an increased risk of pancreatic cancer and it is estimated that 5–10% of patients with pancreatic cancer have an underlying germline disorder. Having a non-O blood group, another inherited characteristic, has also been steadily associated with an increased risk of pancreatic cancer. While many risk factors for pancreatic cancer are not modifiable, adopting a healthy lifestyle could substantially reduce pancreatic cancer risk.
Trends of Primary and Subsequent Cancers of the Gastrointestinal Tract in the Czech Population, 1976–2005
Authors: Dítě Petr , Geryk Edvard
Published: November 2010

A total of 355,624 new gastrointestinal (GI) cancers were registered in 1976–2005 in the Czech Cancer Registry. Of these, there were 14,744 (4.1%) primary and 26,790 (7.5%) subsequent cases, of which all were GI multiple cancers (12.1% males and 11.1% females). The primary GI cancers were followed by 16,362 other neoplasms (60.7% males, 39.3% females); the subsequent GI cancers were preceded by 31,519 other neoplasms (55.8% males, 44.2% females). Double neoplasms were higher in females, and multiple cases were higher in males. The number of primary cases peaked in 1997, the number of subsequent cases increased until 2005. Almost half of the cases were registered in the age group of 50–69 years. The average interval between primary GI cancers and subsequent neoplasms was 6.1 years; the ratio of synchronous to metachronous cases was 1:3.6 in males and 1:5 in females. The most frequent synchronous cases in males were cancers of other GI, urinary, genital and respiratory tract; in females these were cancers of other GI, genital and urinary tract and the breast. The most frequent cancers preceding the next subsequent GI cancer included primary cancers of the skin, other GI, genital, urinary and respiratory tract for males, and those of the skin, genital and other GI tract and breast cancer for females. The 23,462 subsequent GI cancers reported as a 2nd cancer included early stages in 29.6% of males and 27.9% of females, advanced stages in 31.2% males and 31.3% females, and unknown stages in 39.3% males and 40.8% females. Of 3,562 primary neoplasms of advanced stages before subsequent GI cancers, 2,093 were cases at stage III (51.4% males, 48.6% females) and 1,469 cases were at stage IV (60.2% males, 39.8% females); the most frequent in males were primary cancers of other GI, respiratory and genital tract, and cancers of other GI, breast and genital cancers in females. Of 9,568 primary neoplasms before subsequent GI cancers at advantage stages, 3,325 cases were registered before stage III (53.9% males, 46.1% females) and 6,243 cases before stage IV (57.7% males, 42.3% females). The most frequent in males were primary cancers of skin, other GI, genital and urinary tract; for women, the most frequent were those of the skin, genital cancers, breast and other GI tract. Up to October 2007, 78.2% males died and 21.8% survived primary GI cancers; for women, 76.6% of died and 23.4% survived. Of the subsequent GI cancers, 86.7% males died and 13.3% survived; for women, 85.7% died and 14.3% survived.
What’s New in Therapy of Pancreatic Cancer?
Authors: Mössner Joachim
Published: November 2010

Background: Pancreatic cancer remains a dismal disease with a median survival after diagnosis of about 6 months. Methods: Clinical trials with regard to treatment of pancreatic cancer, published as full manuscripts within the last 3 years and available via PubMed, were evaluated. Results: Several factors have positive influences on survival after pancreas resection: well-differentiated tumor grade, low tumor size, no duodenal or major vessel invasion, no perineural invasion, negative lymph node status, resection margin negativity (R0), high-volume centers, presence of human equilibrative nucleoside transporter 1 in patients treated with gemcitabine, low preoperative tumor marker CA 19-9, and low bilirubin level. The following factors seem to have no influence on survival after pancreas resection: age, blood loss and transfusion requirements following resection, location of tumor, and type of resection. Adjuvant chemotherapy after R0 resection is standard: gemcitabine seems to be superior to 5-FU or no therapy. Nevertheless, only a few patients survive for at least 5 years after R0 resection and adjuvant chemotherapy. Most patients need palliative treatment. Besides best supportive care including nutritional support, therapy for pain and endoscopic treatment of jaundice, gemcitabine is standard in both locally advanced and metastatic disease. The addition of the tyrosine kinase inhibitor erlotinib prolongs median survival for only 2 weeks. Erlotinib has only beneficial effects in patients who develop a skin rash. None of the studied combinations of various therapies have demonstrated any additional benefits. Conclusion: There are no real medical breakthroughs with regards to improving the prognosis of pancreatic cancer.
Percutaneous Absorption of Pimecrolimus Is Not Increased in Patients with Moderate to Severe Atopic Dermatitis when Pimecrolimus Cream 1% Is Applied under Occlusion
Authors: Thaçi Diamant , Kaufmann Roland , Bieber Thomas , Hanfland Julia , Hauffe Suzanne , Koehne-Voss Stephan , Waldmeier Felix
Published: November 2010

Aim: To evaluate the systemic exposure of pimecrolimus cream 1% applied under occlusion in atopic dermatitis (AD) patients. Methods: A noncomparative, open-label study conducted in 3 groups of moderate to severe AD patients: A (adults, n = 9), B (adolescents, n = 4) and C (children, n = 6). Pimecrolimus cream 1% was applied twice daily for 8.5 days with overnight occlusion in patients with investigator’s global assessment scores of ≧3 and AD involving at least 30% of their body surface area. Pimecrolimus blood concentrations were analyzed. Results: The highest pimecrolimus blood concentrations observed in adults, adolescents and children were 1.84, 0.55 and 1.29 ng/ml, respectively. Pimecrolimus blood concentrations and affected body surface area showed no apparent correlation. Conclusion: No measurable differences were found in pimecrolimus blood concentrations, efficacy and safety profile when pimecrolimus cream 1% was applied under occlusion versus application without occlusion. These findings reflect the high lipophilic properties of pimecrolimus.
Does the Metastatic Lymph Node Ratio Influence the Disease-Free Survival of Patients with Breast Cancer: Single-Center Experiences
Authors: Oven Ustaalioglu Bala Basak , Bilici Ahmet , Kefeli Umut , Şeker Mesut , Yildirim Emre , Salepci Taflan , Oncel Mustafa , Kement Metin , Gumus Mahmut
Published: November 2010

Background: Axillary lymph nodes (ALNs) are the most important prognostic factor for survival in breast cancer. Pathological evaluation can affect the number of involved lymph nodes. In the current study, we evaluated whether the metastatic lymph node ratio (n ratio) is important in predicting disease-free survival (DFS) for breast cancer patients. Material and Methods: From 802 breast cancer cases, 427 patients with ALN metastasis were analyzed retrospectively. The n ratio was categorized as n ratio 1 (1–10%), n ratio 2 (10.01–50%) and n ratio 3 (>50%). DFS was established according to the Kaplan-Meier method. Predicting risk factors for relapse were analyzed using the Cox proportional hazards model. Results: The n ratio was significantly higher in breast cancer patients with advanced pathologic pT, pN and clinical stage, undifferentiated histology, lymphovascular and extracapsular invasion, more resected ALNs and positive progesterone receptor. In the univariate analysis, multicentricity, necrosis, grade, pN stage, estrogen receptor and progesterone receptor positivity, trastuzumab and neoadjuvant chemotherapy usage, the presence of inflammatory breast cancer and n ratio were found to be important factors in predicting DFS. Multivariate analysis indicated that multicentricity, neoadjuvant chemotherapy, trastuzumab usage and n ratio were significantly associated with prognosis. Conclusions: The n ratio is inexpensive, easily available and a simple prognostic factor for breast cancer patients with positive ALNs.
Assessment of Fatigue in Cancer Patients and Community Dwellers: Validation Study of the Filipino Version of the Brief Fatigue Inventory
Authors: Mendoza Tito R. , Laudico Adriano V. , Wang Xin Shelley , Guo Hong , Matsuda Maria Lourdes , Yosuico Victor D. , Fragante Edilberto P. , Cleeland Charles S.
Published: November 2010

Objective: Clinical trials that might identify effective therapies for cancer-related fatigue, one of the most distressing symptoms experienced by patients, require a validated fatigue assessment tool. We developed and validated a Filipino language version of the Brief Fatigue Inventory (BFI-F) for describing the prevalence and severity of fatigue among Filipino patients with cancer. Methods: We conducted a cross-sectional study in Manila, Philippines, in 206 patients with cancer and 170 age-matched community-dwelling adults who had never had a diagnosis of cancer. Validity and reliability were evaluated by principal factor analysis and Cronbach’s α coefficients. Results: Factor analysis extracted 1 factor, i.e. fatigue severity, with a Cronbach’s α of 0.95; this is consistent with the original BFI English version validation study. Approximately 49% of the patients with cancer had mild fatigue, 34% had moderate fatigue, and 17% had severe fatigue. Patients with a poorer performance status had significantly worse fatigue than patients with a better performance status (5.0 ± 2.8 vs. 3.8 ± 2.2; p < 0.05). Compared with community adults, the patients with cancer reported significantly higher levels of fatigue. Conclusions: The BFI-F had satisfactory internal consistency and validity, and it was able to measure the severity of fatigue and its influence on Filipino cancer patients.
Genotyping of AAV Plasmid Stocks: Quality Control in Adeno-Associated Virus Vector Production
Authors: Schmitt Markus , Pawlita Michael , Kleinschmidt Jürgen
Published: November 2010

Recombinant adeno-associated virus (rAAV) vectors are a promising tool for gene therapy. When multiple serotypes are handled in the same laboratory during the AAV vector production, it is essential to have means to identify the serotype in a sample and to confirm the absence of cross-contaminating AAV sequences in plasmid stocks as well as end products. Here, we describe the development of a Multiplex AAV Genotyping (MAG) assay to type sensitively and specifically DNA from AAV serotypes 1–12 and to detect AAV2 serotype DNA sequences encoding peptide insertions used to modify tissue tropism. MAG is based on multiplex PCR using type-specific primers and subsequent multiplex hybridization by Luminex. The assay is highly specific, and can easily identify plasmid cross-contaminations. Using 10-fold dilution series, the detection limit was below 10 AAV genomes per PCR. In artificial cross-contamination experiments with a 1,000-fold excess of one AAV serotype versus another one, the contaminating type could be still detected with 10–100 AAV genomes. In a first application, MAG identified successfully cross-contaminated AAV plasmid stocks. In conclusion, MAG is a powerful high-throughput tool in assessing the purity and identity of AAV DNA plasmids and other starting materials used for AAV vector production.