bluuebunny/crossref_metadata_2025 huggingface dataset:
Grain Growth Enhancement of Electroplated Copper Film by Supercritical Annealing
Authors: Ueno Kazuyoshi , Shimada Yuji , Yomogida Shigeru , Akahori Seishi , Yamamoto Tomohiko , Yamaguchi Takamasa , Aoki Yoshinori , Matsuyama Akiko , Yata Takashi , Hashimoto Hideki
Published: May 2010

The resistivity increase caused by grain boundary (GB) scattering is a challenging problem in the formation of narrow copper (Cu) interconnects less than 100 nm wide. In order to reduce GB scattering, a new annealing method was successfully developed to enhance the grain growth of electroplated Cu films using supercritical (SC) CO2 with H2. In order to determine the effect of H2, the Cu surface was analyzed using X-ray photoelectron spectroscopy (XPS). The amounts of oxygen (O) and carbon (C) at the Cu surface after SC annealing were reduced with increasing H2 pressure. Surface migration was considered to be enhanced by the reduced amount of O and C, which led to grain growth enhancement. The cross-sectional grain structure in 100-nm-wide interconnect trenches was observed using secondary ion microscopy (SIM). The Cu grains inside the trench were found to be affected by the microstructure in the Cu overburden. Accordingly, Cu grain growth in trenches is also expected to be enhanced by SC annealing.
Plasma-Enhanced Atomic Layer Deposition of Ni
Authors: Lee Han-Bo-Ram , Bang Sung-Hwan , Kim Woo-Hee , Gu Gil Ho , Lee Young Kuk , Chung Taek-Mo , Kim Chang Gyoun , Park Chan Gyung , Kim Hyungjun
Published: May 2010

Ni plasma enhanced atomic layer deposition (PE-ALD) using bis(dimethylamino-2-methyl-2-butoxo)nickel [Ni(dmamb)2] as a precursor and NH3or H2plasma as a reactant was comparatively investigated. PE-ALD Ni using NH3plasma showed higher growth rate, lower resistivity, and lower C content than that using H2plasma. PE-ALD Ni films were analyzed by X-ray photoelectron spectroscopy (XPS), scanning transmission electron microscopy (STEM), and electron energy loss spectroscopy (EELS). The results showed that the reaction chemistry of ALD using NH3plasma was clearly different with that using H2, probably due to the effects of NHxradicals.
Stress Modulation of Silicon Nitride Film by Initial Deposition Conditions for Transistor Carrier Mobility Enhancement
Authors: Tian Jingze , Zuo Biao , Lu Wei , Zhou Meisheng , Hsia Liang Choo
Published: May 2010

Various silicon nitride (SiN) films were prepared using plasma enhanced chemical vapor deposition (PECVD) by tuning deposition condition to control initial hydrogen in the films. The as-deposited films, which exhibit different tensile stress from 0.2 to 1.2 GPa, were treated by ultraviolet (UV) curing to investigate how the stress and shrinkage response to film initial hydrogen state and how to modify SiN hydrogen state by deposition condition to achieve high tensile stress. The results show that the stress and shrinkage of SiN films response quite differentially to UV curing depending on hydrogen state. Stress of SiN was hardly tuned by UV curing in case of Si–H deficiency, but largely increased in case of balanced Si–H and N–H bonds. Both high and low stress-tunable SiN films were used as contact etch stop layer (CAESL) in 45 nm bulk device. Device performance (I
on–I
off) has been improved by about 5% using high stress-tunable SiN film.
Fundamental Study of Chemical–Mechanical Polishing Slurry of Cobalt Barrier Metal for the Next-Generation Interconnect Process
Authors: Nishizawa Hideaki , Nojo Haruki , Isobe Akira
Published: May 2010

A chemical–mechanical polishing (CMP) slurry was developed for use in copper (Cu) damascene interconnects with cobalt (Co) barrier metal by optimizing the corrosion potentials and removal rate selectivities of Cu and Co. A passivation layer was formed on Co surface in an alkaline solution, while no passivation layer was formed in an acidic one even with benzotriazole. In the slurry of pH 10, corrosion potential of Co was the same as that of Cu, which indicates that no galvanic corrosion between Co and Cu could occur. Furthermore, a stable Cu/Co removal rate selectivity of 0.5 was obtained with the slurry.
Performance of Cu Dual-Damascene Interconnects Using a Thin Ti-Based Self-Formed Barrier Layer for 28 nm Node and Beyond
Authors: Ohmori Kazuyuki , Mori Kenichi , Maekawa Kazuyoshi , Kohama Kazuyuki , Ito Kazuhiro , Ohnishi Takashi , Mizuno Masao , Asai Koyu , Murakami Masanori , Miyatake Hiroshi
Published: May 2010

With continuous shrinkage of advanced ultralarge scale integrations (ULSI), the impact of line resistance on the devices has become more and more important. In order to achieve low resistance and high reliability of Cu interconnects, we have applied a thin Ti-based self-formed barrier layer using Cu–Ti alloy seed to 45 nm node dual-damascene interconnects and evaluated its performance. The microstructure analysis by transmission electron microscope and energy dispersive X-ray fluorescence spectrometer has revealed that 2-nm-thick Ti-based barrier layer is self-formed at the interface between Cu and low-k dielectrics. The line resistance and via resistance decrease significantly, compared with those of conventional Ta/TaN barrier system. The stress migration performance is also drastically improved using self-formed barrier process. These results suggest Ti-based self-formed barrier process is one of the most promising candidates for advanced Cu interconnects.
Trench Sidewall Elimination Effect on Line-to-Line Leakage Current in Scalable Porous Silica (k= 2.1)/Cu Interconnect Structure
Authors: Gawase Akifumi , Chikaki Shinichi , Nakamura Naofumi , Soda Eiichi , Oda Noriaki , Saito Shuichi
Published: May 2010

The sidewall film in low-k/copper interconnects is generally applied to protect the etched low-k surface. However, the existence of this film will become a critical issue with shrinking device sizes. In this work, using intermetal low-k film consisting of scalable porous silica (k = 2.1), we tried to eliminate the sidewall film by reducing pore size in 140-nm-pitched scalable porous silica/copper interconnects. Sufficient wiring resistance yield and low wiring capacitance were obtained even in the structure without sidewall. The degradation in the line-to-line leakage caused by the upper layer fabrication process was improved by this sidewall elimination. The mechanism of the leakage degradation was explained by the moisture diffusion from the upper layer, which reacted with the damage site generated by the sidewall formation process.
Chemical Vapor Deposition of GeSbTe Thin Films for Next-Generation Phase Change Memory
Authors: Machida Hideaki , Hamada Seichi , Horiike Takafumi , Ishikawa Masato , Ogura Atsushi , Ohshita Yoshio , Ohba Takayuki
Published: May 2010

In this paper, we describe chemical vapor deposition (CVD) of GeSbTe (GST) films for fabricating phase change memory. A low-carbon-impurity GST film was deposited by CVD. Film composition and structure varied significantly depending on deposition temperature and pressure. The tendency of composition variation on a TiN substrate was the same as that on a SiO2 substrate. Finally, flat Ge2Sb2Te5 thin films were obtained below 300 °C using tert-butylgermanium, triisopropylantimony and diisopropyltellurium as precursors.
Hybrid Electrochemical Mechanical Planarization Process for Cu Dual-Damascene Through-Silicon Via Using Noncontact Electrode Pad
Authors: Tominaga Shigeru , Abe Daisuke , Enomoto Taro , Kondo Seiichi , Kitada Hideki , Ohba Takayuki
Published: May 2010

A hybrid electrochemical mechanical planarization and chemical mechanical planarization (e-CMP/CMP) was applied to the Cu dual-damascene through-silicon via (TSV) process for wafer-level three-dimensional integrated circuit (3D-IC) stacking. In this process, an electrochemically deposited Cu film was removed by e-CMP at a removal rate of 3.5 µm/min until the voltage endpoint was detected. Then, residual Cu film was polished off in the CMP mode using the same e-CMP pad. A fine Cu damascene structure was successfully fabricated with a dishing depth of less than 200 nm in a metal pad of 200×200 µm2 area. The criterion of dishing without failure in the adhesive coat for 3D-IC stacking is discussed.
Interoperable and adaptive fuzzy services for ambient intelligence applications
Authors: Acampora Giovanni , Gaeta Matteo , Loia Vincenzo , Vasilakos Athanasios V.
Published: May 2010

In Ambient Intelligence (AmI) vision, people should be able to seamlessly and unobtrusively use and configure the intelligent devices and systems in their ubiquitous computing environments without being cognitively and physically overloaded. In other words, the user should not have to program each device or connect them together to achieve the required functionality. However, although it is possible for a human operator to specify an active space configuration explicitly, the size, sophistication, and dynamic requirements of modern living environment demand that they have autonomous intelligence satisfying the needs of inhabitants without human intervention. This work presents a proposal for AmI fuzzy computing that exploits multiagent systems and fuzzy theory to realize a long-life learning strategy able to generate context-aware-based fuzzy services and actualize them through abstraction techniques in order to maximize the users' comfort and hardware interoperability level. Experimental results show that proposed approach is capable of anticipating user's requirements by automatically generating the most suitable collection of interoperable fuzzy services.
A towards an extended relational algebra for software architecture
Authors: Li Zude , Gittens Mechelle , Murtaza Syed Shariyar , Madhavji Nazim H.
Published: May 2010

Software architecture is often structured as box-and-arrow graphs and has important implications for system development and maintenance. We propose an
extended relational algebra
to support presentation and manipulation of both architectural structures and implications. The core structure of this algebra is the
extended architectural relation
(EAR). An EAR is a mapping from an architectural relation (AR) to a multi-set of
attributes
(M), where the AR is an ordinary relation representing an architectural structure, and the M represents a multi-set representing a type of architectural implication. A set of
EAR operations
is then defined to support EAR manipulations. The main advantage of this extended algebra over ordinary relational algebras is that the architectural implications (the M part) are presented and manipulated together with the architectural structures (the AR part). This paper first discusses why we propose the algebra, then briefly introduces what the algebra is, and finally describes how to use the algebra in a real scenario.
Measuring reliability growth of software by considering fault dependency, debugging time Lag functions and irregular fluctuation
Authors: Singh V. B. , Kapur P. K. , Tandon Abhishek
Published: May 2010

The progress of software testing is influenced by various uncertainty factors like effort expenditure, skill of test personal, testing tool, defect density, irregular state of open source project, and irregular state of software fault-report phenomena on the bug tracking system. Hence, there is an irregular fluctuation in fault detection/removal rate during testing phase. In software, the independence of failures can hardly be assumed and dependency of faults can also be considered as one of the factor for getting irregular fluctuation. In Literature, various software reliability growth models have been developed by considering fault dependency with various debugging time lag functions. But, none of the models have incorporated irregular fluctuation in their fault detection rate. Therefore, in this paper fault dependency based software reliability growth models have been developed by applying an It ∧o type Stochastic Differential Equations in order to incorporate (i) the irregular fluctuation in the fault detection process due to various uncertainty factor during testing phase and (ii) irregular state of software fault-report phenomena on the bug tracking system. The proposed stochastic differential equation based fault dependency models have been validated using (i) open source software fault count data where software fault-report phenomena on the bug tracking system keep an irregular state and (ii) a fault counting data with minor, major and critical faults. The proposed models have been compared with the existing fault dependency models. Various comparison criteria results for goodness of fit have also been presented in the paper.
DG-metrics formulization for DGML-based software design
Authors: Suri P. K. , Singh Gurdev
Published: May 2010

DGML-based software-design representation uses specially designed XML tags to represent the design elements. This representation opens new possibilities for verifying DGML-based software design against existing design metrics and creation of new design metrics. This paper discusses newly created design metrics for the DGML-based design DG-Metrics. This helps in identifying error prone modules in early stages of software development process, tuning design modules for better performance and in managing the later phases of software development cycle with ease.
PGE2promotes Ca2+-mediated epithelial barrier disruption through EP1and EP4receptors in Caco-2 cell monolayers
Authors: Rodríguez-Lagunas M. José , Martín-Venegas Raquel , Moreno Juan José , Ferrer Ruth
Published: May 2010

We recently demonstrated that PGE2induces the disruption of the intestinal epithelial barrier function. In the present study, our objectives were to study the role of PGE2receptors (EP1–EP4) and the signaling pathways involved in this event. Paracellular permeability (PP) was assessed in differentiated Caco-2 cell cultures from d-mannitol fluxes and transepithelial electrical resistance (TER) in the presence of different PGE2receptor agonists (carbacyclin, sulprostone, butaprost, ONO-AE1-259, ONO-AE-248, GR63799, and ONO-AE1-329) and antagonists (ONO-8711, SC-19220, AH-6809, ONO-AE3-240, ONO-AE3-208, and AH-23848). The results indicate that EP1and EP4but not EP2and EP3might be involved in PP regulation. These effects were mediated through PLC-inositol trisphosphate (IP3)-Ca2+and cAMP-PKA signaling pathways, respectively. We also observed an increase in intracellular Ca2+concentration ([Ca2+]i) strengthened by cAMP formation indicating a cross talk interaction of these two pathways. Moreover, the participation of a conventional PKC isoform was shown. The results also indicate that the increase in PP may be correlated with the redistribution of occludin, zona occludens 1 (ZO-1), and the perijunctional actin ring together with an increase in myosin light chain kinase activity. Although the disruption of epithelial barrier function observed in inflammatory bowel disease (IBD) patients has been traditionally attributed to cytokines, the present study focused on the role of PGE2in PP regulation, as mucosal levels of this eicosanoid are also increased in these inflammatory processes.
Sodium bicarbonate ingestion prior to training improves mitochondrial adaptations in rats
Authors: Bishop David J. , Thomas Claire , Moore-Morris Tom , Tonkonogi Michail , Sahlin Kent , Mercier Jacques
Published: May 2010

We tested the hypothesis that reducing hydrogen ion accumulation during training would result in greater improvements in muscle oxidative capacity and time to exhaustion (TTE). Male Wistar rats were randomly assigned to one of three groups (CON, PLA, and BIC). CON served as a sedentary control, whereas PLA ingested water and BIC ingested sodium bicarbonate 30 min prior to every training session. Training consisted of seven to twelve 2-min intervals performed five times/wk for 5 wk. Following training, TTE was significantly greater in BIC (81.2 ± 24.7 min) compared with PLA (53.5 ± 30.4 min), and TTE for both groups was greater than CON (6.5 ± 2.5 min). Fiber respiration was determined in the soleus (SOL) and extensor digitorum longus (EDL), with either pyruvate (Pyr) or palmitoyl carnitine (PC) as substrates. Compared with CON (14.3 ± 2.6 nmol O2·min−1·mg dry wt−1), there was a significantly greater SOL-Pyr state 3 respiration in both PLA (19.6 ± 3.0 nmol O2·min−1·mg dry wt−1) and BIC (24.4 ± 2.8 nmol O2·min−1·mg dry wt−1), with a significantly greater value in BIC. However, state 3 respiration was significantly lower in the EDL from both trained groups compared with CON. These differences remained significant in the SOL, but not the EDL, when respiration was corrected for citrate synthase activity (an indicator of mitochondrial mass). These novel findings suggest that reducing muscle hydrogen ion accumulation during running training is associated with greater improvements in both mitochondrial mass and mitochondrial respiration in the soleus.
Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-α improves acute myocardial function
Authors: Herrmann Jeremy L. , Abarbanell Aaron M. , Weil Brent R. , Wang Yue , Poynter Jeffrey A. , Manukyan Mariuxi C. , Meldrum Daniel R.
Published: May 2010

Stem cell-based therapies offer promising potential for myocardial infarction (MI), but endogenous molecules released in response to injury likely impair posttransplantation stem cell function. Stem cell-mediated cardioprotection occurs in part via paracrine effects, and transforming growth factor-α (TGF-α) has been shown to enhance paracrine function. However, it is unknown whether pretreating stem cells with TGF-α increases stem cell-mediated cardioprotection after acute MI. Mesenchymal stem cells (MSCs) were treated with TGF-α (250 ng/ml) for 24 h. Adult male Sprague-Dawley rat hearts were isolated and perfused using the Langendorff method. MI was induced by ligating the left anterior descending coronary artery. Postligation (30 min), vehicle or 1 × 106MSCs with or without pretreatment were injected in the infarct border zones, and the hearts were perfused for an additional 60 min. Left ventricular function was continuously measured, and infarct size was assessed with Evans blue dye and 2,3,5-triphenyltetrazolium chloride staining. Myocardial production of interleukin (IL)-1β and IL-6 and caspase 3 activation was also measured. Left ventricular function decreased significantly following coronary artery ligation but improved following injection of untreated MSCs and to a greater extent after injection of pretreated MSCs. In addition, the infarct area, myocardial caspase 3 activation, and IL-6 production were lowest in hearts injected with pretreated cells. Intramyocardial injection of TGF-α-pretreated MSCs after acute MI is associated with increased myocardial function and decreased myocardial injury. This strategy may be useful for optimizing the therapeutic efficacy of stem cells for the treatment of acute MI.
Uric acid increases fibronectin synthesis through upregulation of lysyl oxidase expression in rat renal tubular epithelial cells
Authors: Yang Zhou , Xiaohua Wang , Lei Jiang , Ruoyun Tan , Mingxia Xiong , Weichun He , Li Fang , Ping Wen , Junwei Yang
Published: May 2010

Urate is produced as the major end product of purine metabolism. In the last decade, the incidence of hyperuricemia increased markedly, and similar trends in the epidemiology of metabolic syndrome have been observed. Hyperuricemia is associated with renal disease, and recent studies have reported that mild hyperuricemia results in hypertension, intrarenal vascular disease, and renal injury. This has led to the hypothesis that uric acid may contribute to renal fibrosis and progressive renal disease. Our purpose was to investigate the relationship between uric acid and renal tubular injury. We applied the method of intraperitoneal injection of uric acid to generate the hyperuricemic mouse model. Compared with the saline injection group, the expression of lysyl oxidase (LOX) and fibronectin in kidneys was increased significantly in hyperuricemic groups. In vitro, uric acid significantly induced NRK-52E cells to express the ECM marker fibronectin, as well as LOX, which plays a pivotal role in ECM maturation, in a time- and dose-dependent manner. Upregulation of the urate transporter URAT1, which is located in the apical membrane of proximal tubules, sensitized the uric acid-induced fibronectin and LOX induction, while both knocking down URAT1 expression in tubular epithelial cells by RNA interference and inhibiting URAT1 function pharmacologically attenuated LOX and fibronectin expression. Furthermore, knockdown of LOX expression by a small interfering RNA strategy led to a decrease in fibronectin abundance induced by uric acid treatment. In addition, evidence of a uric acid-induced activation of the NF-κB signaling cascade was observed. Our findings highlight a need for carefully reevaluating our previous view on the pathological roles of hyperuricemia in the kidney and nephropathy induced by uric acid in clinical practice.
Selective renal overexpression of human heat shock protein 27 reduces renal ischemia-reperfusion injury in mice
Authors: Kim Minjae , Park Sang Won , Kim Mihwa , Chen Sean W. C. , Gerthoffer William T. , D'Agati Vivette D. , Lee H. Thomas
Published: May 2010

We have previously shown that exogenous and endogenous A1adenosine receptor (A1AR) activation protected against renal ischemia-reperfusion (IR) injury in mice by induction and phosphorylation of heat shock protein 27 (HSP27). With global overexpression of HSP27 in mice, however, there was a paradoxical increase in systemic inflammation with increased renal injury after an ischemic insult due to increased NK1.1 cytotoxicity. In this study, we hypothesized that selective renal expression of HSP27 in mice would improve renal function and reduce injury after IR. Mice were subjected to renal IR injury 2 days after intrarenal injection of saline or a lentiviral construct encoding enhanced green fluorescent protein (EGFP) or human HSP27 coexpressing EGFP (EGFP-huHSP27). Mice with kidney-specific reconstitution of huHSP27 had significantly lower plasma creatinine, renal necrosis, apoptosis, and inflammation as demonstrated by decreased proinflammatory cytokine mRNA induction and neutrophil infiltration. In addition, there was better preservation of the proximal tubule epithelial filamentous (F)-actin cytoskeleton in the huHSP27-reconstituted groups than in the control groups. Furthermore, huHSP27 overexpression led to increased colocalization with F-actin in renal proximal tubules. Taken together, these findings have important clinical implications, as they imply that kidney-specific expression of HSP27 through lentiviral delivery is a viable therapeutic option in attenuating the effects of renal IR.
Clinical Benefit of Second-Line Palliative Chemotherapy in Advanced Soft-Tissue Sarcoma
Authors: Minchom Anna , Jones Robin L. , Fisher Cyril , Al-Muderis Omar , Ashley Sue , Scurr Michelle , Karavasilis Vasilios , Judson Ian R.
Published: May 2010

Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma.Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewing's sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control.Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7%) achieved disease control. Median duration of response was 11 months (95% CI: 9–13). On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1%) patients who failed to respond to first-line therapy achieved disease control. Eight (2.1%) patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7–10 months). On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival.Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients.
Pricing Equity‐Indexed Annuities under Stochastic Interest Rates Using Copulas
Authors: Gaillardetz Patrice
Published: May 2010

We develop a consistent evaluation approach for equity‐linked insurance products under stochastic interest rates. This pricing approach requires that the premium information of standard insurance products is given exogenously. In order to evaluate equity‐linked products, we derive three martingale probability measures that reproduce the information from standard insurance products, interest rates, and equity index. These risk adjusted martingale probability measures are determined using copula theory and evolve with the stochastic interest rate process. A detailed numerical analysis is performed for existing equity‐indexed annuities in the North American market.
Postural Instability Is Associated with Brain Atrophy and Cognitive Impairment in the Elderly: The J-SHIPP Study
Authors: Kido Tomoko , Tabara Yasuharu , Igase Michiya , Ochi Namiko , Uetani Eri , Nagai Tokihisa , Yamamoto Miyuki , Taguchi Keiko , Miki Tetsuro , Kohara Katsuhiko
Published: May 2010

Background/Aims: Mobility impairment in older adults has been suggested to be a marker of subclinical structural and functional brain abnormalities. We investigated a possible association between static postural instability and brain abnormalities and cognitive decline. Methods: The study subjects were 390 community residents without definitive dementia (67 ± 7 years old) and 21 patients with Alzheimer’s disease (AD). Brain atrophy was measured by MRI. Results: The mobility of the posturography-measured center of gravity (COG) was positively associated with the temporal horn area (THA; r = 0.260; p < 0.001). Subjects who could not stand on one leg for >40 s (n = 102) showed a significantly larger THA (22 ± 18 vs. 14 ± 11 × 10–2 cm2; p < 0.001). Multiple regression analysis identified COG path length (β = 0.118; p = 0.032) and one-leg standing time (β = 0.176; p = 0.001) as independent determinants of THA. Mild cognitive impairment (MCI) subjects (n = 61) had a significantly enlarged THA compared to that of normal cognitive subjects (22 ± 16 vs. 16 ± 13 × 10–2 cm2; p = 0.002). AD patients showed a more enlarged THA (78 ± 55 × 10–2 cm2). Subjects with cognitive decline showed a significantly shorter one-leg standing time (normal: 50 ± 17 s; MCI: 42 ± 21 s; AD: 18 ± 20s; p < 0.001). Conclusion: Reduced postural stability was an independent marker of brain atrophy and pathological cognitive decline in the elderly.
Utilization of CO2 Laser for Temporal Fascia Graft Welding in Myringoplasty: An Experimental Study on Guinea Pigs
Authors: Youssef Tarek Fouad , Ahmed Mohamed Rifaat , Kassab Ahmed Nazmi
Published: May 2010

An experimental study was undertaken to investigate the use of a CO2 laser welding technique in myringoplasty. Albumin solder was used to fix a temporal fascia graft via an overlay transcanal approach. The results of the operative procedure were assessed by microscopic and histopathologic examination over an interval of 1, 2, 3 and 4 weeks postoperatively. Materials and Methods: Forty-eight adult guinea pigs were divided into two groups after permanent perforation of the tympanic membrane was created: laser-assisted myringoplasty group and surgical myringoplasty group. Laser beam power was 0.4 W, pulse duration 0.75 s, pulse interval 0.1 s and spot size 250 µm. Each experimental group was further subdivided into four subgroups of 6 animals each. Histological and microscopic findings of the tympanic membrane for both groups after 1, 2, 3, and 4 weeks were compared. Results: Microscopic examination of the tympanic membrane showed high success rate in the laser-assisted myringoplasty group compared to the control group. Histological evaluation for the tympanic membrane showed complete repair of the tympanic membrane in the laser-assisted myringoplasty group. Conclusion: Laser-assisted myringoplasty using CO2 might be a promising new method in surgical myringoplasty.
Diagnose und Behandlung des Gestationsdiabetes – das Grazer Modell
Authors: Panzitt T. , Zeck W. , Mayer-Pickel K.
Published: May 2010

Fragestellung: Trotz der Häufigkeit des Gestationsdiabetes (GDM) wird ein Grossteil der betroffenen Fälle nicht erkannt oder unzureichend therapiert. Problematisch sind ein genereller Trend zur Unterschätzung des Morbiditätsrisikos, eine fehlende Verankerung des GDM in den Mutterschaftsrichtlinien, sowie uneinheitliche Leitlinien zu Screening und Therapie des GDM. Methoden: Das Grazer Modell zu Diagnostik und Therapie des GDM bietet seit Jahrzehnten ein einstufiges generelles Screening aller Schwangeren zwischen der 24. und 28. Schwangerschaftswoche (SSW) an; zusätzlich ermöglicht die Option der Bestimmung der Fruchtwasserinsulinkonzentration mittels Amniozentese in der 31.–32. SSW die Erfassung von hyperinsulinämischen Feten, die ein geburtshilfliches Hochrisikokollektiv darstellen. Schlussfolgerungen: Die im Vergleich zu anderen Richtlinien niedrigeren Grenzwerte des oralen Glukosetoleranztests sowie das Angebot zur Bestimmung der Fruchtwasserinsulinkonzentration, welche im Grazer Konzept seit langer Zeit verankert sind, ermöglichen eine höhere Erkennungsrate sowie eine zielgerichtete Therapie von Hochrisikofällen. Screening und Therapie des GDM stellen kosteneffiziente Massnahmen zur Verbesserung des geburtshilflichen Outcomes dar, weshalb die Forderung nach einer Verankerung des GDM in den Mutterschaftsrichtlinien nachdrücklich vertreten werden soll.
Diabetes mellitus in der Schwangerschaft – eine psychische Belastung?
Authors: Mautner E. , Dorfer M.
Published: May 2010

Die Betreuung von Schwangeren mit diabetischer Stofflage stellt ein bedeutsames und wachsendes Feld in der täglichen klinischen Praxis dar. In den letzten Jahren wurde vermehrt untersucht, inwieweit Diabetes mellitus mit psychischen Belastungen verbunden ist, und wie sich dies auf die medizinische Behandlung auswirkt. In der vorliegenden Übersichtsarbeit werden sowohl Studien zu manifestem Diabetes als auch zu Gestationsdiabetes präsentiert. Ausserdem werden Einflussfaktoren auf das Gesundheitsverhalten beschrieben. Besonders manifester Diabetes ist mit grosser psychischer Belastung verbunden und sollte von Klinikern beachtet und behandelt werden. Eine intensive medizinische und psychologische Betreuung in einer speziellen Diabetesambulanz, die Ernährungs- und Bewegungsberatung einschliesst, ist für alle Diabetikerinnen zu empfehlen, um eine bestmögliche Selbstkontrolle und Eigenverantwortung der Frauen zu gewährleisten.
Dilemma Schwangerschaftsdiabetes: Weltweite Unterschiede in Diagnostik und Therapie
Authors: Zeck W. , Schlembach D. , Panzitt T. , Lang U. , McIntyre H.D.
Published: May 2010

Fragestellung: Gestationsdiabetes mellitus (GDM) sowie Diabetes mellitus der Typen 1 und 2 in der Schwangerschaft stellen für die Mutter, den Feten und das Neugeborene während der Schwangerschaft, intra- und postpartal bzw. in den nachfolgenden Jahren ein hohes Risiko dar. Es wurde erhoben, inwieweit sich geburtshilfliche Zentren auf unterschiedlichen Kontinenten im Management dieser Erkrankung unterscheiden. Methoden: Im Rahmen einer wissenschaftlichen Kooperation zwischen der Abteilung für Frauenheilkunde und Geburtshilfe der Medizinischen Universitätsklinik Graz, Österreich, und dem Centre of Obstetric Medicine am Mater Misericordiae Mothers’ Hospital in Brisbane, Australien, wurde versucht, Diagnostik und Therapie von «Diabetes in der Schwangerschaft» an den beiden Tertiärkliniken zu vergleichen. Ergebnisse: Das Management von Schwangeren mit Diabetes mellitus der Typen 1 und 2 war nahezu ident, während im Bereich des Managements von GDM erhebliche Unterschiede gefunden wurden. Schlussfolgerung: Die Standardisierung von Screeningkriterien und diagnostischen Methoden im Bereich des GDM und des vor der Schwangerschaft bestehenden Diabetes erscheint immer noch schwierig. Ein nationaler und internationaler Konsens muss letztlich gefunden werden, um der prophezeiten «Diabetesepidemie» Einhalt zu gebieten.
Nachweis von Mikrokalk durch hochauflösende B-Mode-Sonographie bei BI-RADS-4a-Patientinnen
Authors: Stöblen F. , Landt S. , Köninger A. , Hecktor J. , Kimmig R. , Kümmel S.
Published: May 2010

Ziel: Evaluation der diagnostischen Wertigkeit der hochauflösenden B-Mode-Sonographie zum Nachweis von Mikrokalk und mikrokalkassoziierten Herdbefunden bei Patientinnen mit BI-RADS-4a-Läsionen. Patientinnen und Methode: Bei 40 Patientinnen wurden eine Röntgenmammographie und eine B-Mode-Sonographie mit 13 MHz durchgeführt. Untersucht wurden: mit Röntgenmammographie: Ausdehnung der Mikrokalkareale und Darstellbarkeit assoziierter Herdbefunde; mit Ultraschall: Sensitivität des Mikrokalknachweises, Qualität der Darstellung, Ausdehnung der Mikrokalkareale, Darstellbarkeit assoziierter Herdbefunde und Durchführbarkeit einer ultraschallgestützten Biopsie. Ergebnisse: In der Röntgenmammographie betrug die mittlere Ausdehnung von Mikrokalkarealen 28 ± 21 mm. Sensitivität, Spezifität, positiver (PPV) und negativer prädiktiver Wert (NPV) und die Nachweisgenauigkeit mikrokalkassoziierter Herdbefunde betrugen 61,5, 57,9, 50, 45,8 und 47,5%. Die B-Mode-Sonographie erreichte eine Sensitivität von 100%. Die mittlere Ausdehnung der Mikrokalkareale betrug sonographisch 7 ± 3 mm und war damit signifikant geringer (p < 0,01). Es ergaben sich für Sensitivität, Spezifität, PPV, NPV und die Nachweisgenauigkeit 14,3, 84,2, 50, 47,1 und 47,5%. Die Durchführung einer ultraschallgestützten Biopsie erschien bei 22 (55%) Patientinnen möglich. Schlussfolgerung: Die Hochfrequenz-B-Mode-Sonographie ermöglicht einen hoch sensitiven Nachweis von Mikrokalk bei BI-RADS-4a-Läsionen und lässt eine ultraschallgestützte Biopsie bei etwa der Hälfte der Patientinnen durchführbar erscheinen.
Comparison of Aerosol and Intranasal Challenge in a Mouse Model of Allergic Airway Inflammation and Hyperresponsiveness
Authors: Swedin Linda , Ellis Russ , Kemi Cecilia , Ryrfeldt Åke , Inman Mark , Dahlén Sven-Erik , Adner Mikael
Published: May 2010

Background: The aim was to optimize antigen challenge for induction of airway hyperresponsiveness (AHR) and inflammation in BALB/c mice sensitized to ovalbumin (OVA). Comparisons were made between mice challenged with OVA either as an aerosol or intranasally. The protocol that induced maximal AHR in BALB/c mice was thereafter tested in C57BL/6 mice. Method: Methacholine responsiveness was measured using the flexiVent® system to assess AHR. Inflammatory responses were investigated by histology and cell counts in bronchoalveolar lavage (BAL) fluid. Results: 48 h after challenge with 1 or 6% OVA aerosols, there were similar increments in AHR and BAL cells, predominantly eosinophils. When comparing the effect of 1% OVA aerosol on AHR and cell infiltration at 24 and 48 h after challenge, the responses were similar. At 24 h, intranasal OVA administration (20–200 µg) caused a dose-dependent increase in AHR. BAL cells were increased by all intranasal OVA doses and to a greater extent than after 1% OVA aerosol challenge but without any dose dependency. Histological examination confirmed that there was an increase of eosinophils in lung tissue following either challenge. In C57BL/6 mice, baseline tissue elastance was the only functional outcome that was increased after intranasal OVA challenge. Even though the AHR response was negligible in C57BL/6 mice, a similar infiltration of BAL cells was observed in both strains. Conclusion: Intranasal challenge was more effective than aerosol challenge at inducing both AHR and airway inflammation in BALB/c mice. Although intranasal challenge caused airway inflammation in C57BL/6 mice, this strain is not optimal for studying AHR.
Interleukin 13 and Interleukin 4 Receptor-α Polymorphisms in Rhinitis and Asthma
Authors: Bottema Renske W.B. , Nolte Ilja M. , Howard Timothy D. , Koppelman Gerard H. , Dubois Anthony E.J. , de Meer Gea , Kerkhof Marjan , Bleecker Eugene R. , Meyers Deborah A. , Postma Dirkje S.
Published: May 2010

Background: Asthma and rhinitis may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. IL13 and IL4R polymorphisms are associated with asthma and show gene-gene interaction in asthma. Their role in rhinitis has not been extensively studied. Methods: Association of IL13 and IL4R polymorphisms in relation to rhinitis, asthma, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with rhinitis who were clinically not affected by asthma; (2) 407 trios with an asthmatic proband, and (3) 118 asthma cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. Results: IL13 C–1111T (rs1800925) was significantly associated with rhinitis and atopic phenotypes in rhinitis trios that were not affected by clinical asthma. IL13 Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with asthma and serum IgE in both asthma populations. IL4R Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with asthma in the asthma case-control population. Combining risk genotypes of IL13 Arg130Gln with IL4R Glu375Ala, and IL13 C–1111T with IL4R Ser478Pro yielded increased risks for asthma compared to their separate effects. Conclusion:IL13 polymorphisms were associated with asthma and rhinitis without clinical asthma; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of IL13 and IL4R polymorphisms in asthma.
Nationwide Cross-Sectional Population-Based Study on the Prevalences of Asthma and Asthma Symptoms among Japanese Adults
Authors: Fukutomi Yuma , Nakamura Hiroyuki , Kobayashi Fumio , Taniguchi Masami , Konno Satoshi , Nishimura Masaharu , Kawagishi Yukio , Watanabe Junko , Komase Yuko , Akamatsu Yasuhiro , Okada Chiharu , Tanimoto Yasushi , Takahashi Kiyoshi , Kimura Tomoaki , Eboshida Akira , Hirota Ryoji , Ikei Junko , Odajima Hiroshi , Nakagawa Takemasa , Akasawa Akira , Akiyama Kazuo
Published: May 2010

Background: Asthma is a common respiratory disease worldwide. However, few reports are available on the prevalences of asthma and asthma symptoms among Asian subjects. Methods: To determine the prevalences of asthma and asthma symptoms among Japanese subjects, we performed a nationwide cross-sectional, population-based study on Japanese adults aged 20–79 years. Ten areas spread throughout the country were randomly selected. Door-to-door or postal surveys were performed using a translated version of the European Community Respiratory Health Survey questionnaire. Results: The survey was completed by 23,483 participants. The overall response rate was 70.6%. The prevalences of wheeze and current asthma among all participants aged 20–79 years were 10.1% (95% CI: 9.7–10.5%) and 4.2% (95% CI: 4.0–4.5%), respectively. The prevalences among young adults aged 20–44 years were 9.3% (95% CI: 8.7–9.9%) and 5.3% (95% CI: 4.8–5.8%), respectively. The prevalence of current asthma was highest in females aged 30–39 years in comparison with the other gender and age groups. Conclusions: This nationwide study determined the prevalences of asthma and asthma symptoms among Japanese adults. The results provide fundamental information on the respiratory health of Japanese adults.
Involvement of Galectin-9 in Lung Eosinophilia in Patients with Eosinophilic Pneumonia
Authors: Katoh Shigeki , Nobumoto Atsuya , Matsumoto Nobuhiro , Matsumoto Kiyoshi , Ehara Naomi , Niki Toshiro , Inada Hiroyuki , Nishi Nozomu , Yamauchi Akira , Fukushima Kiyoyasu , Hirashima Mitsuomi
Published: May 2010

Background: Although we first found galectin-9 (Gal-9) as an eosinophil chemoattractant, its role in eosinophilic inflammation is still obscure. The purpose of the present study is to clarify the role of Gal-9 in human eosinophilic pulmonary inflammation in comparison with eotaxin (CCL11). Methods: We measured the levels of Gal-9 and eotaxin in the bronchoalveolar lavage fluid (BALF) of patients with acute and chronic eosinophilic pneumonia (AEP and CEP). Furthermore, the biological activities (chemotaxis and apoptosis) of Gal-9 were compared with those of eotaxin using interleukin-5-primed or -unprimed eosinophils. Results: The levels of Gal-9 and eotaxin in the BALF from patients with AEP and those with CEP were higher than those found in the controls. Although there was little difference in Gal-9 level between patients with AEP and patients with CEP, the eotaxin level was significantly lower in patients with CEP. In patients with AEP, the eosinophil number correlated well with both the Gal-9 and eotaxin levels. However, in patients with CEP, the eosinophil number only correlated well with the Gal-9 level. Moreover, the Gal-9 level correlated with the eotaxin level in patients with AEP, but there was no significant correlation between those levels in patients with CEP. Anti-Gal-9 antibody treatment strongly reduces eosinophil chemotactic activity in the BALF of patients with AEP and in that of patients with CEP, whereas the anti-CCR3 (receptor for eotaxin) antibody strongly reduces this activity in the BALF of patients with AEP but not in that of patients with CEP. Furthermore, Gal-9 exhibited both chemotactic and proapoptotic activities for activated eosinophils, though eotaxin only exhibited chemotactic activity. Conclusions: The present results provide two possibilities: that Gal-9 is involved in pulmonary eosinophilia in patients with AEP and CEP, and that Gal-9 exhibits regulatory functions for activated eosinophils at the site of inflammation.
Fasting Serum Adiponectin Level Inversely Correlates with Metabolic Syndrome in Peritoneal Dialysis Patients
Authors: Wang Chih-Hsien , Wang Ji-Hung , Lee Chung-Jen , Fang Te-Chao , Liou Hung-Hsiang , Hsu Bang-Gee
Published: May 2010

Background:Metabolic syndrome is a significant risk factor for cardiovascular disease and predicts hospitalization in peritoneal dialysis (PD) patients. An inverse association between circulating adiponectin and metabolic syndrome has been observed in humans. However, no data are available on the relationship between metabolic syndrome and serum adiponectin levels in PD patients. Method: Fasting blood samples were obtained from 47 PD patients and 47 subjects in an outpatient department were enrolled as a control group. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation. Adiponectin levels were measured using a commercial enzyme immunoassay kit. Results: Twenty-seven of 47 PD patients (57.5%) had metabolic syndrome. PD patients had lower serum albumin (p < 0.001) and higher serum adiponectin levels (p = 0.016), high-sensitivity C-reactive protein (p = 0.008), creatinine (p < 0.001) and metabolic syndrome (p < 0.001) than controls. The fasting adiponectin level inversely correlated with the metabolic syndrome in these PD patients (p = 0.006). Univariate linear regression analysis showed that the waist circumference (r = –0.304; p = 0.038), body mass index (r = –0.347; p = 0.017), body fat mass (r = –0.305; p = 0.037), white blood count (r = –0.631; p < 0.001), triglyceride (TG; r = –0.526; p < 0.001), and fasting glucose (r = –0.394; p = 0.006) were negatively correlated with the fasting serum adiponectin levels, while high-density lipoprotein-cholesterol (r = 0.443; p = 0.002) was positively correlated with the fasting serum adiponectin levels among the PD patients. Multivariate forward stepwise linear regression analysis of the significant variables showed that white blood count (R2 change = 0.398, p < 0.001), and TG (R2 change = 0.118, p = 0.002) were the independent predictors of fasting serum adiponectin levels and explained 51.6% of variance. Conclusions: We observed that PD patients had higher metabolic syndrome than the general population and an inverse association was found between the circulating fasting adiponectin level and metabolic syndrome in PD patients. White blood count and TG were independent predictors of the serum adiponectin level among PD patients.
Correlation of Treatment Time and Ultrafiltration Rate with Serum Albumin and C-Reactive Protein Levels in Patients with End-Stage Kidney Disease Receiving Chronic Maintenance Hemodialysis: A Cross-Sectional Study
Authors: Zsom Lajos , Zsom Marianna , Fülöp Tibor , Wells Catherine , Flessner Michael F. , Eller József , Wollheim Charlotta , Hegbrant Jörgen , Strippoli Giovanni F.M.
Published: May 2010

Background: The relationship between treatment time, ultrafiltration rate (UFR) and inflammation has received limited exploration so far. Methods: This is a cross-sectional cohort study of 12 hemodialysis clinics. Statistical models explored the association of multiple patient- and dialysis-specific covariates with low albumin (≤40 g/l) or high C-reactive protein (CRP) (>5 mg/dl) and calculated the ORs and 95% CIs. Results: 616 patients with a mean age of 60.9 ± 14.4 years participated in our study. Mean treatment time was 237.3 ± 23.8 min and mean UFR was 7.0 ± 4.0 ml/kg/h. In stepwise logistic regression, treatment time >4 h reduced the risk of low albumin (OR 0.397, 95% CI 0.235–0.672, p < 0.001). Congestive heart failure (OR 1.634, 95% CI 1.154–2.312, p = 0.006) and acute infection (OR 1.799, 95% CI 1.059–3.056, p = 0.03) were significant correlates of the risk of high CRP. There was no association between UFR and either CRP or albumin. Conclusion: Treatment time had a significant cross-sectional association with serum albumin but not with CRP.
Properties of the ‘Timed Up and Go’ Test: More than Meets the Eye
Authors: Herman Talia , Giladi Nir , Hausdorff Jeffrey M.
Published: May 2010

Background: The ‘timed up and go’ test (TUG) is a simple, quick and widely used clinical performance-based measure of lower extremity function, mobility and fall risk. We speculated that its properties may be different from other performance-based tests and assessed whether cognitive function may contribute to the differences among these tests in a cohort of healthy older adults. Objective: To evaluate psychometric properties of the TUG in healthy older adults in comparison to the Berg balance test (BBT) and the Dynamic Gait Index (DGI). Methods: The TUG, DGI and BBT were assessed in 265 healthy older adults (76.4 ± 4.3 years; 58.3% women) who participated in a 3-year prospective study. The Mini-Mental State Examination, digit span and verbal fluency measured cognitive function. The one-sample Kolmogorov-Smirnov test evaluated deviations from a normal distribution and Pearson’s correlation coefficients quantified associations. Results: The mean scores of the BBT, DGI and TUG were: 54.0 ± 2.4, 22.8 ± 1.5, 9.5 ± 1.7 s, respectively. The BBT and the DGI were not normally distributed (p < 0.001), but the TUG was (p = 0.713). The TUG times were mildly associated (p < 0.01) with digit span and verbal fluency and were related to future falls, while the BBT and the DGI were not. Conclusions: The TUG appears to be an appropriate tool for clinical assessment of functional mobility even in healthy older adults. It does not suffer from ceiling effect limitations, is normally distributed and is apparently related to executive function. The BBT and the DGI do not share these beneficial properties. Perhaps the transferring and turning components of the TUG help to convert this relatively simple motor task into a more complex measure that also depends on cognitive resources.