bluuebunny/crossref_metadata_2025 huggingface dataset:
DESIGN AND PERFORMANCE EVALUATION OF A FUZZY-BASED TRAFFIC CONDITIONER FOR MOBILE AD HOC NETWORKS
Authors: TORSHIZ MASOOD NIAZI , MOVAGHAR ALI
Published: March 2009

A mobile ad hoc network is a collection of mobile hosts forming a temporary network on the fly, without using any fixed infrastructure. Characteristics of mobile ad hoc networks such as lack of central coordination, mobility of hosts, dynamically varying network topology, and limited availability of resources make QoS provisioning very challenging in such networks.

In this paper, we introduce a fuzzy QoS traffic conditioner for mobile ad hoc networks. The proposed traffic conditioner consists of fuzzy admission control (FAC), fuzzy traffic rate controller (FTRC), and fuzzy scheduler (FS).

The proposed FAC monitors the delay and available bandwidth and decides whether to accept or reject the request. The FTRC uses the additive increase multiplicative decrease (AIMD) rate control algorithm as a base, in which a node increments its transmission rate when the observed delay is below the predefined threshold, with an increment rate of c Kbps and decreases its transmission rate by r% when the delay passes the threshold. FTRC accepts the packet delay and the "delay-threshold d" as inputs and calculates c and r by using a set of fuzzy rules. The third part of the proposed traffic conditioner is FS, which is based on the traditional weighted round robin (WRR) mechanism. FS monitors the packet drop and delay of each queue and adjusts the queue weights by using a fuzzy inference engine.
ON EXPONENTIAL STABILITY FOR STOCHASTIC DELAY PARTIAL DIFFERENTIAL EQUATIONS
Authors: YU GUOSHENG , LIU BING
Published: March 2009

This paper is concerned with the exponential stability of energy solutions to a nonlinear stochastic delay partial differential equations with finite delay in separable Hilbert spaces. Some exponential stability criteria are obtained by constructing the Lyapunov function. As an application, one example is also given to illustrate our results.
THE EXISTENCE AND UNIQUENESS FOR NON-LIPSCHITZ STOCHASTIC NEUTRAL DELAY EVOLUTION EQUATIONS DRIVEN BY POISSON JUMPS
Authors: LUO JIAOWAN , TANIGUCHI TAKESHI
Published: March 2009

In this paper, we consider the existence and uniqueness of mild solutions to non-Lipschitz stochastic neutral delay evolution equations driven by Poisson jump processes: [Formula: see text] with an initial function X(s) = φ(s), -r ≤ s ≤ 0, where φ : [-r, 0] → H is a cadlag function with [Formula: see text].
THE HAUSDORFF DIMENSION OF HORSESHOES UNDER RANDOM PERTURBATIONS
Authors: SHU LIN
Published: March 2009

We study the distribution of the set of future generic points for an ergodic measure of a bundle random dynamical system; and prove that the Hausdorff dimension of a two dimensional horseshoe is stable under random perturbations.
COMBINED THEORY OF NONRELATIVISTIC AND QUASIRELATIVISTIC ATOMIC INTEGRALS OVER INTEGER AND NONINTEGER N-SLATER-TYPE ORBITALS
Authors: GUSEINOV I. I.
Published: March 2009

One- and two-electron nonrelativistic and quasirelativistic basic functions are introduced. The combined analytical relations in terms of these basic functions are derived for the non- and quasi-relativistic atomic integrals over integer and noninteger n-Slater-type orbitals. The relationships obtained are valid for the arbitrary values of principal quantum numbers and screening constants of Slater orbitals.
A CASE STUDY OF THE "TOWARDS 2010" PROGRAMME HEALTH IMPACT ASSESSMENT
Authors: ALI SHAUKAT , O'CALLAGHAN VICKY , MIDDLETON JOHN D.
Published: March 2009

A health impact assessment case study of an innovative "Towards 2010" programme aiming to bring together health and social care organisations is described. The aim of the assessment was to inform the decision makers which of the four service reconfiguration options being considered would bring about significant benefits to the health and wellbeing of the local population. Overall, 600 positive and negative impacts were predicted across 11 broad determinants of health including employment and economy, education, transport, housing, visual amenity (environment), access to services, crime, lifestyle, pollution, health inequalities and family and social cohesion. The findings suggest that two of the four options seem to offer the best opportunity for improving the health and wellbeing of the local population and for linking into wider regeneration initiatives within the programme area. The outcome of the HIA places decision makers in a better informed position to develop appropriate policies for maximising positive and mitigating negative aspects of the proposals.
Glutathione-S-transferase P protects against endothelial dysfunction induced by exposure to tobacco smoke
Authors: Conklin Daniel J. , Haberzettl Petra , Prough Russell A. , Bhatnagar Aruni
Published: March 2009

Exposure to tobacco smoke impairs endothelium-dependent arterial dilation. Reactive constituents of cigarette smoke are metabolized and detoxified by glutathione- S-transferases (GSTs). Although polymorphisms in GST genes are associated with the risk of cancer in smokers, the role of these enzymes in regulating the cardiovascular effects of smoking has not been studied. The P isoform of GST (GSTP), which catalyzes the conjugation of electrophilic molecules in cigarette smoke such as acrolein, was expressed in high abundance in the mouse lung and aorta. Exposure to tobacco smoke for 3 days (5 h/day) decreased total plasma protein. These changes were exaggerated in GSTP−/−mice. Aortic rings isolated from tobacco smoke-exposed GSTP−/−mice showed greater attenuation of ACh-evoked relaxation than those from GSTP+/+mice. The lung, plasma, and aorta of mice exposed to tobacco smoke or acrolein (for 5 h) accumulated more acrolein-adducted proteins than those tissues of mice exposed to air, indicating that exposure to tobacco smoke results in the systemic delivery of acrolein. Relative to GSTP+/+mice, modification of some proteins by acrolein was increased in the aorta of GSTP−/−mice. Aortic rings prepared from GSTP−/−mice that inhaled acrolein (1 ppm, 5 h/day for 3 days) or those exposed to acrolein in an organ bath showed diminished ACh-induced arterial relaxation more strongly than GSTP+/+mice. Acrolein-induced endothelial dysfunction was prevented by pretreatment of the aorta with N-acetylcysteine. These results indicate that GSTP protects against the endothelial dysfunction induced by tobacco smoke exposure and that this protection may be related to the detoxification of acrolein or other related cigarette smoke constituents.
Sex differences and central protective effect of 17β-estradiol in the development of aldosterone/NaCl-induced hypertension
Authors: Xue Baojian , Badaue-Passos Daniel , Guo Fang , Gomez-Sanchez Celso E. , Hay Meredith , Johnson Alan Kim
Published: March 2009

The present study tested the hypotheses that male and female rats respond differently to subcutaneous infusions of aldosterone (Aldo; 1.8 μg·kg−1·h−1, 1% NaCl to drink; 28 days) and that central estrogen plays a protective role against the development of hypertension. In rats with blood pressure (BP) and heart rate (HR) measured by Data Sciences International telemetry, chronic Aldo/NaCl treatment induced a greater increase in BP in males (Δ25.4 ± 2.4 mmHg) than in females (Δ7.1 ± 2.2 mmHg). Gonadectomy augmented Aldo/NaCl-induced hypertension in females (Δ18.2 ± 2.0 mmHg) but had no effect in males (Δ23.1 ± 2.9 mmHg). Immunohistochemistry for Fra-like activity was higher in the paraventricular nucleus of intact males, castrated males, and ovariectomized (OVX) females compared with intact females after 28 days of Aldo/NaCl treatment. In intact males, central 17β-estradiol (E2) inhibited the Aldo/NaCl increase in BP (Δ10.5 ± 0.8) compared with that in central vehicle plus systemic Aldo/NaCl (Δ26.1 ± 2.5 mmHg) rats. Combined administration of E2and estrogen receptor antagonist ICI182780 (ICI) blocked the protective effect of E2(Δ23.2 ± 2.4 mmHg). In intact females central, but not peripheral, infusions of ICI augmented the Aldo/NaCl (Δ20.4 ± 1.8 mmHg) BP increase. Finally, ganglionic blockade after Aldo infusions resulted in a smaller reduction in BP in intact females (−23.9 ± 2.5 mmHg) and in central estrogen-treated males (−30.2 ± 1.0 mmHg) compared with other groups (intact males, −39.3 ± 3.4; castrated males, −41.8 ± 1.9; intact males with central E2+ ICI, −42.3 ± 2.1; OVX females, −40.3 ± 3.3; and intact females with central ICI, −39.1 ± 1.3 mmHg). Chronic Aldo infusion produced increases in NaCl intake and decreases in HR that were both similar in all groups. Taken together, the results indicate that central estrogen plays a protective role in the development of Aldo/NaCl-induced hypertension and that this may result from reduced sympathetic outflow.
Transforming growth factor-β1 causes pulmonary microvascular endothelial cell apoptosis via ALK5
Authors: Lu Qing , Patel Bhuvic , Harrington Elizabeth O. , Rounds Sharon
Published: March 2009

We have previously shown that transforming growth factor (TGF)-β1 protected against main pulmonary artery endothelial cell (PAEC) apoptosis induced by serum deprivation and VEGF receptor blockade through a mechanism associated with ALK5-mediated Bcl-2 upregulation. In the current study, we investigated the effect of TGF-β1 on pulmonary microvascular endothelial cell (PMVEC) apoptosis. We found that, in contrast to the results seen in conduit PAEC, TGF-β1 caused apoptosis of PMVEC, an effect that was also dependent on ALK5 activity. We noted that non-SMAD signaling pathways did not play a role in TGF-β1-induced apoptosis. Both SMAD2 and SMAD1/5 were activated upon exposure to TGF-β1. TGF-β1-induced activation of SMAD2, but not SMAD1/5, was abolished by ALK5 inhibition, an effect that associated with prevention of TGF-β1-induced apoptosis. These results suggest that SMAD2 is important in TGF-β1-induced apoptosis of PMVEC. While caspase-12 activity was not altered, caspase-8 was activated by TGF-β1, an effect that correlated with a reduction of cFLIP protein levels. Additionally, TGF-β1 decreased Bcl-2 protein levels and induced cytochrome c cytosolic redistribution. These results suggest that TGF-β1 caused apoptosis of PMVEC likely through both caspase-8-dependent extrinsic pathway and mitochondria-mediated intrinsic pathway. We noted that inhibition of ALK5 attenuated serum deprivation-induced apoptosis, an effect that correlated with increased expression and activation of CREB and its potential target genes, Bcl-2 and cFLIP. These results suggest that CREB may be important in mediating apoptosis resistance of PMVEC upon ALK5 inhibition perhaps through upregulation of Bcl-2 and cFLIP. Finally, we noted that SMAD1/5 were activated upon ALK5 inhibition in the presence of low levels of TGF-β1, an effect associated with enhanced endothelial proliferation. We speculate that imbalance of ALK1 and ALK5 may contribute to the development of pulmonary artery hypertension.
MMP9 modulates tight junction integrity and cell viability in human airway epithelia
Authors: Vermeer Paola D. , Denker James , Estin Miriam , Moninger Thomas O. , Keshavjee Shaf , Karp Philip , Kline Joel N. , Zabner Joseph
Published: March 2009

The family of zinc- and calcium-dependent matrix metalloproteases (MMPs) play an important role in remodeling of the airways in disease. Transcriptional regulation by proinflammatory cytokines increases lymphocyte-derived MMP9 levels in the airway lumen of asthmatics. Moreover, the levels of the MMP9 inhibitor, tissue inhibitor of metalloprotease (TIMP1), are decreased leading to increased protease activity. The mechanism by which MMP9 activity leads to asthma pathogenesis and remodeling remains unclear. Using a model of well-differentiated human airway epithelia, we found that apical MMP9 significantly increases transepithelial conductance. Moreover, apical MMP9 treatment decreased immunostaining of tight junction proteins suggesting disruption of barrier function. Consistent with this, viruses gained access to the epithelial basolateral surface after MMP9 treatment, which increased infection efficiency. All of these effects were blocked by TIMP1. In addition, loss of epithelial integrity correlated with increased epithelial cell death. Thus we hypothesized that MMP9 exerts its effects on the epithelium by cleaving one or more components of cell-cell junctions and triggering anoikis. Taken together, these data suggest that a component of airway remodeling associated with asthma may be directly regulated by MMP9.
Loss of Thy-1 inhibits alveolar development in the newborn mouse lung
Authors: Nicola Teodora , Hagood James S. , James Masheika L. , MacEwen Mark W. , Williams Timothy A. , Hewitt Matthew M. , Schwiebert Lisa , Bulger Arlene , Oparil Suzanne , Chen Yiu-Fai , Ambalavanan Namasivayam
Published: March 2009

Transforming growth factor (TGF)-β mediates hypoxia-induced inhibition of alveolar development in the newborn lung. TGF-β is regulated primarily at the level of activation of latent TGF-β. Fibroblasts expressing Thy-1 (CD90) inhibit TGF-β activation. We hypothesized that loss of Thy-1 due to hypoxia may be a mechanism by which hypoxia increases TGF-β activation and that animals deficient in Thy-1 will simulate the effects of hypoxia on lung development. To determine if loss of Thy-1 occurred during hypoxia, non-transgenic (C57BL/6) wild-type (WT) mice exposed to hypoxia were evaluated for Thy-1 mRNA and protein. To determine if Thy-1 deficiency simulated hypoxia, WT and Thy-1 null ( Thy-1−/−) mice were exposed to air or hypoxia from birth to 2 wk, the critical period of lung development, and lung histology, function, parameters related to TGF-β signaling, and extracellular matrix protein content were measured. To test if the phenotype in Thy-1−/−mice was due to excessive TGF-β signaling, measurements were also performed in Thy-1−/−mice administered TGF-β neutralizing antibody (1D11). We observed that hypoxia reduced Thy-1 mRNA and Thy-1 staining in WT mice. Thy-1−/−mice had impaired alveolarization, increased TGF-β signaling, reduced lung epithelial and endothelial cell proliferation but increased fibroblast proliferation, and increased collagen and elastin. Lung compliance was lower, and tissue but not airway resistance was higher in Thy-1−/−mice at 2 wk. Thy-1−/−mice given 1D11 had improved alveolar development and lung function. These data support the hypothesis that hypoxia, by reducing Thy-1, increases TGF-β activation, and thereby inhibits normal alveolar development.
Aflatoxin B1 Exposure, Hepatitis B Virus Infection, and Hepatocellular Carcinoma in Taiwan
Authors: Wu Hui-Chen , Wang Qiao , Yang Hwai-I , Ahsan Habibul , Tsai Wei-Yann , Wang Li-Yu , Chen Shu-Yuan , Chen Chien-Jen , Santella Regina M.
Published: March 2009

To evaluate the role of aflatoxin B1 (AFB1) exposure on risk of hepatocellular carcinoma (HCC), a case-control study nested within a community-based cohort was conducted. Baseline blood and urine samples were used to determine the level of AFB1-albumin adducts and urinary AFB1 metabolites. Conditional logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) to assess the effect of AFB1 exposure on risk of HCC. The adjusted ORs (95% CIs) were 1.54 (1.01-2.36) and 1.76 (1.18-2.58), respectively, for those with AFB1-albumin adducts and urinary AFB1 metabolite levels above the mean compared with those with levels below the mean. When compared with subjects in the lowest quartile of urinary AFB1 metabolites, there was an increase in risk of HCC, with adjusted ORs (95% CIs) of 0.57 (0.14-2.43), 1.43 (0.32-6.42), and 4.91 (1.18-20.48; Ptrend = 0.02), respectively, among noncarriers of hepatitis B virus (HBV) infection. The adjusted OR (95% CI) was 7.49 (5.13-10.93) for carriers of hepatitis B surface antigen compared with noncarriers, regardless of AFB1 status. The ORs (95% CI) were 10.38 (5.73-18.82) and 15.13 (7.83-29.25) for carriers of hepatitis B surface antigens with levels of AFB1-albumin adducts and urinary AFB1 metabolites above the mean, respectively. The combined effect of aflatoxin exposure and HBV infection did not differ by duration of follow-up. Consistent with our previous study with fewer subjects, these data show that AFB1 exposure is a risk factor for HCC risk. However, in this larger study, the effect of combined AFB1 exposure and HBV infection is more consistent with an additive than a multiplicative model. (Cancer Epidemiol Biomarkers Prev 2009;18(3):846–53)
IGF-IandIGFBP-3Polymorphisms in Relation to Circulating Levels among African American and Caucasian Women
Authors: D'Aloisio Aimee A. , Schroeder Jane C. , North Kari E. , Poole Charles , West Suzanne L. , Travlos Gregory S. , Baird Donna D.
Published: March 2009

Circulating insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels have been associated with common diseases. Although family-based studies suggest that genetic variation contributes to circulating IGF-I and IGFBP-3 levels, analyses of associations with multiple IGF-I and IGFBP-3 single nucleotide polymorphisms (SNP) have been limited, especially among African Americans. We evaluated 30 IGF-I and 15 IGFBP-3 SNPs and estimated diplotypes in association with plasma IGF-I and IGFBP-3 among 984 premenopausal African American and Caucasian women. In both races, IGFBP-3 rs2854746 (Ala32Gly) was positively associated with plasma IGFBP-3 (CC versus GG mean difference among Caucasians, 631 ng/mL; 95% confidence interval, 398-864; African Americans, 897 ng/mL; 95% confidence interval, 656-1,138), and IGFBP-3 diplotypes with the rs2854746 GG genotype had lower mean IGFBP-3 levels than reference diplotypes with the CG genotype, whereas IGFBP-3 diplotypes with the CC genotype had higher mean IGFBP-3 levels. IGFBP-3 rs2854744 (-202 A/C) was in strong linkage disequilibrium with rs2854746 in Caucasians only, but was associated with plasma IGFBP-3 in both races. Eight additional IGFBP-3 SNPs were associated with ≥5% differences in mean IGFBP-3 levels, with generally consistent associations between races. Twelve IGF-I SNPs were associated with ≥10% differences in mean IGF-I levels, but associations were generally discordant between races. Diplotype associations with plasma IGF-I did not parallel IGF-I SNP associations. Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians but provides less evidence that IGF-I SNPs affect plasma IGF-I levels. (Cancer Epidemiol Biomarkers Prev 2009;18(3):954–66)
Human Papillomavirus Types by Age in Cervical Cancer Precursors: Predominance of Human Papillomavirus 16 in Young Women
Authors: Porras Carolina , Rodríguez Ana Cecilia , Hildesheim Allan , Herrero Rolando , González Paula , Wacholder Sholom , Burk Robert D. , Schiffman Mark
Published: March 2009

In a population-based study conducted in Guanacaste, Costa Rica, we investigated the human papillomavirus (HPV) types detected in 233 cases of cervical intraepithelial neoplasia (CIN) 2/3 and cancer by age. CIN2+ and CIN3+ in young women were significantly more likely to be associated with HPV 16 than the same lesions in older women (80% of CIN3+ were associated with HPV 16 among women ages 18-26 years compared with only 32% among women older than 55 years; Ptrend = 0.018). There were no differences by age in HPV 18 positivity. Lesions in older women were mainly caused by other carcinogenic types. This association was present for both prevalent and incident lesions and supports the notion that HPV 16 is a stronger carcinogen than other HPV types. It also has implications for prevention, including the need to vaccinate young women before exposure to HPV vaccine–containing types (HPV 16 and HPV 18) to prevent the majority of cervical cancer precursors. (Cancer Epidemiol Biomarkers Prev 2009;18(3):863–5)
Persistence of an Incident Human Papillomavirus Infection and Timing of Cervical Lesions in Previously Unexposed Young Women
Authors: Trottier Helen , Mahmud Salaheddin M. , Lindsay Lisa , Jenkins David , Quint Wim , Wieting Susan L. , Schuind Anne , Franco Eduardo L. ,   on behalf of the GSK HPV-001 Vaccine Study Group
Published: March 2009

Background: We analyzed data from a cohort of 553 women enrolled in the placebo arm of a randomized controlled trial of the human papillomavirus (HPV) 16/18 vaccine to study the timing of the occurrence of squamous intraepithelial lesions (SIL) or cervical intraepithelial neoplasia (CIN) following incident HPV infection and its relation to persistence of the infection.

Methods: At entry, women were cytologically negative, HPV 16/18 seronegative, and high-risk HPV (HR-HPV) DNA negative. Cervicovaginal samples were initially collected at 3-month and cervical samples at 6-month intervals. We estimated the mean time to SIL/CIN, relative risks of SIL/CIN following incident HPV, and odds ratios between persistent HPV and SIL/CIN.

Results: The mean time for SIL/CIN detection was 43.3 [95% confidence interval (95% CI), 36.4-50.1] and 46.4 (95% CI, 42.0-50.7) months from first infection with HPV 16/18 and other HR-HPVs, respectively. Relative risks of SIL/CIN following incident HPV infection were 66.2 (95% CI, 14.9-295.1) for HPV 16/18 and 50.9 (95% CI, 11.5-225.4) for other HR-HPVs. The odds ratios of SIL/CIN for persistent HPV 16/18 infection, defined as a minimum of two and three (6 monthly) visits, were, respectively, 169.0 (95% CI, 37.2-768.6) and 169.1 (95% CI, 31.5-907.4). The majority of women with cervical infection with HPV 16/18 lasting >6 months (33 of 51, 65%) developed SIL and/or CIN.

Conclusions: These analyses provide the first actuarial estimate of mean time between incident HR-HPV infection in previously uninfected women and onset of cervical lesion development. Persistent HR-HPV infection, particularly HPV 16/18, is a strong predictor of cervical lesion risk and potentially a reliable end point for clinical HPV research. (Cancer Epidemiol Biomarkers Prev 2009;18(3):854–62)
Polymorphic Variation in NFKB1 and Other Aspirin-Related Genes and Risk of Hodgkin Lymphoma
Authors: Chang Ellen T. , Birmann Brenda M. , Kasperzyk Julie L. , Conti David V. , Kraft Peter , Ambinder Richard F. , Zheng Tongzhang , Mueller Nancy E.
Published: March 2009

We found that regular use of aspirin may reduce the risk of Hodgkin lymphoma (HL), a common cancer of adolescents and young adults in the United States. To explore possible biological mechanisms underlying this association, we investigated whether polymorphic variation in genes involved in nuclear factor-κB (NF-κB) activation and inhibition, other inflammatory pathways, and aspirin metabolism influences HL risk. Twenty single nucleotide polymorphisms (SNP) in seven genes were genotyped in DNA from 473 classical HL cases and 373 controls enrolled between 1997 and 2000 in a population-based case-control study in the Boston, Massachusetts, metropolitan area and the state of Connecticut. We selected target genes and SNPs primarily using a candidate-SNP approach and estimated haplotypes using the expectation-maximization algorithm. We used multivariable logistic regression to estimate odds ratios (OR) for associations with HL risk. HL risk was significantly associated with rs1585215 in NFKB1 (AG versus AA: OR, 2.1; 95% confidence interval, 1.5-2.9; GG versus AA: OR, 3.5; 95% confidence interval, 2.2-5.7, Ptrend = 1.7 × 10−8) and with NFKB1 haplotypes (Pglobal = 6.0 × 10−21). Similar associations were apparent across categories of age, sex, tumor EBV status, tumor histology, and regular aspirin use, although statistical power was limited for stratified analyses. Nominally significant associations with HL risk were detected for SNPs in NFKBIA and CYP2C9. HL risk was not associated with SNPs in IKKA/CHUK, PTGS2/COX2, UDP1A6, or LTC4S. In conclusion, genetic variation in the NF-κB pathway seems to influence risk of HL. Pooled studies are needed to detect any heterogeneity in the association with NF-κB across HL subgroups, including aspirin users and nonusers. (Cancer Epidemiol Biomarkers Prev 2009;18(3):976–86)
Primary Cilia and Signaling Pathways in Mammalian Development, Health and Disease
Authors: Veland Iben R. , Awan Aashir , Pedersen Lotte B. , Yoder Bradley K. , Christensen Søren T.
Published: March 2009

Although first described as early as 1898 and long considered a vestigial organelle of little functional importance, the primary cilium has become one of the hottest research topics in modern cell biology and physiology. Primary cilia are nonmotile sensory organelles present in a single copy on the surface of most growth-arrested or differentiated mammalian cells, and defects in their assembly or function are tightly coupled to many developmental defects, diseases and disorders. In normal tissues, the primary cilium coordinates a series of signal transduction pathways, including Hedgehog, Wnt, PDGFRα and integrin signaling. In the kidney, the primary cilium may function as a mechano-, chemo- and osmosensing unit that probes the extracellular environment and transmits signals to the cell via, e.g., polycystins, which depend on ciliary localization for appropriate function. Indeed, hypomorphic mutations in the mouse ift88 (previously called Tg737) gene, which encodes a ciliogenic intraflagellar transport protein, result in malformation of primary cilia, and in the collecting ducts of kidney tubules this is accompanied by development of autosomal recessive polycystic kidney disease (PKD). While PKD was one of the first diseases to be linked to dysfunctional primary cilia, defects in this organelle have subsequently been associated with many other phenotypes, including cancer, obesity, diabetes as well as a number of developmental defects. Collectively, these disorders of the cilium are now referred to as the ciliopathies. In this review, we provide a brief overview of the structure and function of primary cilia and some of their roles in coordinating signal transduction pathways in mammalian development, health and disease.
Feasibility of Real-Time MRI With a Novel Carbon Catheter for Interventional Electrophysiology
Authors: Nordbeck Peter , Bauer Wolfgang R. , Fidler Florian , Warmuth Marcus , Hiller Karl-Heinz , Nahrendorf Matthias , Maxfield Michelle , Wurtz Sabine , Geistert Wolfgang , Broscheit Jens , Jakob Peter M. , Ritter Oliver
Published: March 2009

Background—

Cardiac MRI offers 3D real-time imaging with unsurpassed soft tissue contrast without x-ray exposure. To minimize safety concerns and imaging artifacts in MR-guided interventional electrophysiology (EP), we aimed at developing a setup including catheters for ablation therapy based on carbon technology.

Methods and Results—

The setup, including a steerable carbon catheter, was tested for safety, image distortion, and feasibility of diagnostic EP studies and radiofrequency ablation at 1.5 T. MRI was performed in 3 different 1.5-T whole-body scanners using various receive coils and pulse sequences. To assess unintentional heating of the catheters by radiofrequency pulses of the MR scanner in vitro, a fluoroptic thermometry system was used to record heating at the catheter tip. Programmed stimulation and ablation therapy was performed in 8 pigs. There was no significant heating of the carbon catheters while using short, repetitive radiofrequency pulses from the MR system. Because there was no image distortion when using the carbon catheters, exact targeting of the lesion sites was possible. Both atrial and ventricular radiofrequency ablation procedures including atrioventricular node modulation were performed successfully in the scanner. Potential complications such as pericardial effusion after intentional perforation of the right ventricular free wall during ablation could be monitored in real time as well.

Conclusion—

We describe a newly developed EP technology for interventional electrophysiology based on carbon catheters. The feasibility of this approach was demonstrated by safety testing and performing EP studies and ablation therapy with carbon catheters in the MRI environment.
Mutations in Sodium Channel β1- and β2-Subunits Associated With Atrial Fibrillation
Authors: Watanabe Hiroshi , Darbar Dawood , Kaiser Daniel W. , Jiramongkolchai Kim , Chopra Sameer , Donahue Brian S. , Kannankeril Prince J. , Roden Dan M.
Published: March 2009

Background—

We and others have reported mutations in the cardiac predominant sodium channel gene
SCN5A
in patients with atrial fibrillation (AF). We also have reported that
SCN1B
is associated with Brugada syndrome and isolated cardiac conduction disease. We tested the hypothesis that mutations in the 4 sodium channel β-subunit genes
SCN1B
–
SCN4B
contribute to AF susceptibility.

Methods and Results—

Screening for mutations in the 4 β-subunit genes was performed in 480 patients with AF (118 patients with lone AF and 362 patients with AF and cardiovascular disease) and 548 control subjects (188 ethnically defined anonymized subjects and 360 subjects without AF). The effects of mutant β-subunits on
SCN5A
mediated currents were studied using electrophysiological studies. We identified 2 nonsynonymous variants in
SCN1B
(resulting in R85H, D153N) and 2 in
SCN2B
(R28Q, R28W) in patients with AF. These occur at residues highly conserved across mammals and were absent in control subjects. In 3 of 4 mutation carriers, the ECGs showed saddleback-type ST-segment elevation in the right precordial leads. Transcripts encoding both
SCN1B
and
SCN2B
were detected in human atrium and ventricle. In heterologous expression studies using Chinese hamster ovary cells, the mutant β1- or β2-subunits reduced
SCN5A
-mediated current and altered channel gating compared with coexpression of wild-type subunits.

Conclusions—

Loss of function mutations in sodium channel β-subunits were identified in patients with AF and were associated with a distinctive ECG phenotype. These findings further support the hypothesis that decreased sodium current enhances AF susceptibility.
Spatiotemporal Organization of the Left Atrial Substrate After Circumferential Pulmonary Vein Isolation of Atrial Fibrillation
Authors: Lin Yenn-Jiang , Tai Ching-Tai , Kao Tsair , Chang Shih-Lin , Lo Li-Wei , Tuan Ta-Chuan , Udyavar Ameya R. , Wongcharoen Wanwarang , Hu Yu-Feng , Tso Han-Wen , Tsai Wen-Chin , Chang Chien-Jung , Ueng Kuo-Chang , Higa Satoshi , Chen Shih-Ann
Published: March 2009

Background—

There is a paucity of data regarding the mechanism of maintaining atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with AF. The aim of this study was to examine the impact of circumferential PVI on the left atrial (LA) substrate characteristics.

Methods and Results—

Seventy-two AF patients (age, 53�11 years) underwent mapping and catheter ablation using an NavX system. The biatrial characteristics such as the complex fractionated atrial electrograms (CFEs; based on fractionated intervals) and frequency analysis (based on dominant frequencies) were mapped before and after PVI. PVI with electric isolation was performed in all patients. In the 45 patients who did not respond to PVI, the continuous CFEs (>8 seconds, 18�18% and 12�17% of the LA sites, before and after PVI, respectively,
P
=0.02), degree of LA fractionation (mean fractionated interval: 75.6�14.3 msec versus 87.3�16.7 msec,
P
=0.001), and mean LA dominant frequencies (6.92�0.88 Hz versus 6.58�0.91 Hz,
P
=0.001) decreased after PVI. Complete PVI altered the distribution of the CFEs toward the LA anteroseptum, mitral annulus, and LA appendage regions. A persistent presence of continuous CFEs in the vicinity of the dominant frequencies sites (observed in 53% patients) correlated with a higher procedural AF termination rate for the CFE ablation (63% versus 23%,
P
<0.05).

Conclusions—

Complete PVI eliminated some CFEs in the LA and altered the distribution of the CFEs. The persistent presence of CFEs before and after PVI in the vicinity of the high frequency sites is important for AF maintenance after PVI.
Prediction of Ventricular Tachyarrhythmias by Intracardiac Repolarization Variability Analysis
Authors: Tereshchenko Larisa G. , Fetics Barry J. , Domitrovich Peter P. , Lindsay Bruce D. , Berger Ronald D.
Published: March 2009

Background—

Arrhythmic sudden cardiac death (SCD) is generally mediated by ventricular fibrillation (VF) or fast ventricular tachycardia (FVT). We studied the predictive value of temporal QT variability detected from various sources of cardiac electric signal: surface ECG, far-field (FF), and near-field (NF) intracardiac electrograms (EGMs) in patients with implantable cardioverter-defibrillators (ICDs).

Methods and Results—

Surface ECG and FF and NF intracardiac EGMs were simultaneously recorded at rest (mean heart rate, 74�15 bpm) for 4.5�1.3 minutes in 298 patients (mean age, 59�14; 216 male [73%]) with structural heart disease and an implanted Medtronic ICD for primary (231 patients, 78%) or secondary (67 patients, 22%) prevention of SCD. During mean follow-up of 16�8 months, 52 (13.1% per person-year of follow-up) patients sustained VT/VF and received appropriate ICD therapies, but only 19 (4.8% per person-year of follow-up) patients sustained FVT/VF with cycle length ≤240 ms. The Kaplan–Meier survival analysis showed that the highest QT variability index (QTVI) quartile from all cardiac sources (surface ECG; NF and FF EGMs) is associated with event-free survival (
P
=0.038 for ECG;
P
=0.024 for FF EGM;
P
=0.012 for NF EGM). QTVI was a predictor of all VT/VF events and FVT/VF in the multivariate Cox model (including ischemic or nonischemic cardiomyopathy, history of revascularization procedures, LVEF, New York Heart Association class). Strong significant correlation among QTVI determined from all 3 sources was found.

Conclusion—

Repolarization lability is present throughout the ventricular myocardium. Increased intracardiac QT variability predicts VT/VF events in patients with structural heart disease.
Impact of NAD(P)H Oxidase-Derived Reactive Oxygen Species on Coronary Arterial Remodeling
Authors: Terashima Mitsuyasu , Ohashi Yoshitaka , Azumi Hiroshi , Otsui Kazunori , Kaneda Hideaki , Awano Kojiro , Kobayashi Seiichi , Honjo Tomoyuki , Suzuki Takahiko , Maeda Kazumi , Yokoyama Mitsuhiro , Inoue Nobutaka
Published: March 2009

Background—

Coronary arterial remodeling, which is a response to the growth of atherosclerotic plaques, is associated with plaque vulnerability. Oxidative stress induced by reactive oxygen species (ROS) via NAD(P)H oxidase in the vasculature also plays a crucial role in the pathogenesis of atherosclerosis-based cardiovascular disease. In this study, the relationship between coronary arterial remodeling and ROS generation was examined by comparing preinterventional intravascular ultrasound findings of atherosclerotic lesions to the histochemical findings of corresponding specimens obtained by directional coronary atherectomy.

Methods and Results—

Predirectional coronary atherectomy intravascular ultrasound images of 49 patients were analyzed. The remodeling index was calculated by dividing the target-lesion external elastic membrane cross-sectional area by the reference-segment external elastic membrane cross-sectional area. Expansive remodeling was defined as a remodeling index of >1.0. ROS generation and NAD(P)H oxidase p22
phox
expression in directional coronary atherectomy specimens were evaluated using the dihydroethidium staining method and immunohistochemistry as the ratio of the positive area to the total surface area in each specimen, respectively. ROS generation and p22
phox
expression were significantly greater in lesions with expansive remodeling than in lesions without remodeling (0.18�0.12 versus 0.03�0.02,
P
<0.0001, 0.10�0.08 versus 0.04�0.05,
P
=0.0039, respectively). Both ROS generation and p22
phox
expression significantly correlated with the intravascular ultrasound-derived remodeling index (
r
=0.77,
P
<0.0001,
r
=0.53,
P
<0.0001, respectively).

Conclusions—

Simultaneous examination with intravascular ultrasound and immunohistochemistry analyses suggests that NAD(P)H oxidase-derived ROS is related to the coronary arterial remodeling process associated with plaque vulnerability.
The Vicissitudes of Corruption
Authors: Lennerfors Thomas Taro
Published: March 2009

This thesis explores different manifestations of corruption structured around the notion of modernity. It claims that the modern definition is related to transgression. It also maps out a premodern alternative based on degeneration of character, as well as a psychoanalytical understanding related to stolen enjoyment. This thesis is a study of corruption as bribe taking in purchasing and procurement in the Swedish context. The empirical study is based on an explorative, hermeneutic approach and is conducted as a case study at the Swedish Road Administration—a public procurer of road construction and maintenance work. It holds that the modern understanding of corruption is problematic and that different theoretical alternatives can deepen one’s understanding of corruption.
Technoscientific Normativity and the ‘‘Iron Cage’’ of Law
Authors: Bora Alfons
Published: March 2009

Participation of a broad variety of actors in decision-making processes has become an important issue in science and technology policy. Many authors claim the involvement of stakeholders and of the general public to be a core condition for legitimate and sustainable decision making. In the last decades, a wide spectrum of procedures has been developed to realize biotechnological citizenship. These procedures, composed of multiactor arenas, are either located in close relation to the system of politics, or, as in the case of administrative decision making, more closely to the system of law. In the latter case, a problematic constellation arises. Here, law and science can build a technoscientific normativity that systematically excludes political discourse. The law, although intending to provide for political freedom and citizenship rights, at the end appears to be an ‘‘iron cage’’ for political communication.
Higher-Order Fertility Among Urban Fathers
Authors: Bronte-Tinkew Jacinta , Ryan Suzanne , Franzetta Kerry , Manlove Jennifer , Lilja Emily
Published: March 2009

The study includes a longitudinal sample of 1,989 fathers from the Fragile Families and Child Wellbeing study and examines factors associated with fathering a higher-order birth (three or more children) and compares these factors to those predicting any subsequent birth. Also, the article examines differences by marital status. Logistic regression analyses indicate the likelihood of fathering a higher-order birth is greater among more disadvantaged men in urban contexts, those with lower levels of education, the unmarried, minorities, and those exhibiting higher levels of depressive symptomology. This suggests that the men likely to be least prepared to father large numbers of children have an elevated probability of having a higher-order birth. This study provides continuing evidence that several aspects of men's lives in urban contexts have important influences on their decisions to have a higher-order birth, and suggests that policies or programs that address fertility issues should include fathers where and when feasible.
Organizational Traits, Care Processes, and Burnout Among Chronic Hemodialysis Nurses
Authors: Flynn Linda , Thomas-Hawkins Charlotte , Clarke Sean P.
Published: March 2009

In light of evidence linking registered nurse (RN) staffing levels to patient outcomes in chronic hemodialysis facilities, U.S. government regulations have set minimum RN staffing requirements during dialysis. Consequently, facility administrators are focused on decreasing nurse attrition in this crucial practice setting. This study used a cross-sectional, correlational design to investigate the effects of workload, practice environment, and care processes on burnout among nurses in U.S. chronic hemodialysis centers and to determine the association between burnout and nurses' intentions to leave their jobs. Findings indicate that predictors were associated with an increased likelihood of nurse burnout and that nurses experiencing burnout were more likely to be planning to leave their jobs. Findings have important implications for retention of nurses, enhancement of patient safety, and adherence to new federal staffing requirements in chronic hemodialysis units.
Modafinil for the treatment of fatigue in lung cancer: a pilot study
Authors: Spathis A , Dhillan R , Booden D , Forbes K , Vrotsou K , Fife K
Published: March 2009

Cancer-related fatigue is the most prevalent and distressing symptom experienced by patients with advanced cancer. Central nervous system stimulants have been shown to relieve fatigue in nonmalignant disease. Modafinil is a stimulant with a selective site of action in the brain that is better tolerated than traditional stimulants, such as methylphenidate. The aim of this study was to determine the feasibility of conducting a randomised controlled trial to assess the efficacy and safety of modafinil for the treatment of fatigue in patients with lung cancer. Twenty patients with non-small cell lung cancer were recruited to this open-label study. Modafinil was taken in a fixed dose-titration schedule of 100 mg daily for 7 days followed by 200 mg daily for 7 days. Fifteen patients completed the study. During the study period, there was a rapid and statistically significant reduction in the primary outcome, fatigue ( P = 0.001) and the secondary outcomes of daytime sleepiness and depression/anxiety. This improvement in fatigue was also clinically significant. Ten patients chose to continue modafinil after the study and the drug was well-tolerated. It would be both feasible and worthwhile to conduct a definitive randomised controlled trial to determine the role of modafinil in the treatment of cancer-related fatigue.
Multiple sources: mapping the literature of palliative care
Authors: Tieman JJ , Sladek RM , Currow DC
Published: March 2009

Palliative care is an increasingly important area of clinical practice and health service delivery. The heterogeneity of the patient population and the multidisciplinary nature of care draw on knowledge from many fields of clinical practice and academic enquiry. This has implications for the retrieval of evidence and literature and the spread of new knowledge in palliative care. This study shows that the CINAHL, Embase and PsycINFO bibliographic databases hold sizeable repositories of palliative care articles not indexed on Medline. It also highlights the number and range of journals publishing palliative care content. In 2005 alone, 1985 journals published 6983 items. These findings show the challenges for palliative care professionals in managing the complex evidence base for this diverse field of care and the importance of mechanisms that facilitate the identification of palliative care information. Dissemination strategies that ensure that new knowledge reaches the many audiences implicit in the range of journals publishing palliative care are also critical in supporting improvements in clinical practice and service delivery.
Academic Competence for Adolescents Who Bully and Who Are Bullied
Authors: Ma Lang , Phelps Erin , Lerner Jacqueline V. , Lerner Richard M.
Published: March 2009

School bullying has negative implications for adolescent academic competence, making it important to explore what factors promote such competence for adolescents who bully and who are bullied. Potential contextual and individual variables linked to academic competence were examined in the context of bullying. Data were derived from the Grades 5 and 6 of the 4-H Study of Positive Youth Development, a national longitudinal investigation of adolescents in the United States that began in 2002. Longitudinal random effects hierarchical regression analyses with a subsample of 620 adolescents indicated that being a bully negatively impacted academic competence beyond demographic background, including sex and maternal education, and prior year academic competence. Concurrent random effects hierarchical regression analyses of a subsample of 250 adolescents suggested that educational expectations and school engagement interacted in fostering academic competence for bullies and victims. These findings highlight the importance of addressing academic competence in bullying interventions.
Bullying and Victimization Among Native and Immigrant Adolescents in Norway
Authors: Fandrem Hildegunn , Strohmeier Dagmar , Roland Erling
Published: March 2009

This study compares levels of bullying others, victimization, and aggressiveness in native Norwegian and immigrant adolescents living in Norway and shows how bullying is related to proactive and reactive aggressiveness. The sample consists of 2,938 native Norwegians (1,521 girls, 1,417 boys) and 189 immigrant adolescents (97 girls, 92 boys) in school grades 8, 9, and 10. Data were collected via self-assessments. Structural equation models were conducted separately for girls and boys in both groups. The levels of victimization, reactive and proactive aggressiveness were the same for both native Norwegians and immigrant adolescents but there was a significant difference in the levels of bullying others. Compared with the native Norwegians, immigrant adolescents were found to be at higher risk of bullying others. Structural models revealed significantly stronger relations between affiliation-related proactive aggressiveness and bullying others in immigrant boys compared with the other groups. This indicates that the wish for affiliation is an important mechanism of bullying others in immigrant boys. We also suggest further research and the practical importance of the findings for prevention of targeting immigrant adolescents.
Global Self-Esteem, Appearance Satisfaction, and Self-Reported Dieting in Early Adolescence
Authors: Barker Erin T. , Bornstein Marc H.
Published: March 2009

Global self-esteem, appearance satisfaction, and self-reported dieting are interrelated. This study examines the temporal ordering of global self-esteem and appearance satisfaction across the early adolescence transition, from age 10 to age 14, as well as the independent associations of self-esteem and appearance satisfaction on self-reported dieting at age 14. Participants were 130 firstborn European American adolescents (40% girls). Adolescents who were less satisfied with their appearance at age 10 reported declines in self-esteem from age 10 to age 14. Adolescents with lower global self-esteem at age 10 did not decline in appearance satisfaction. Girls, adolescents with higher body mass index scores at age 10, and adolescents who were less satisfied with their appearance at age 14 all reported more frequent dieting at age 14. Implications for etiological and intervention models of eating problems in adolescence are considered.
Cultural Identity and Peer Influence as Predictors of Substance Use Among Culturally Diverse Australian Adolescents
Authors: Gazis Nicki , Connor Jason P. , Ho Robert
Published: March 2009

This study investigated cultural identity and peer influence on tobacco, alcohol, and cannabis use in a culturally diverse sample of Northern Australian adolescents. Middle school students ( n = 274) completed the Multigroup Ethnic Identity Measure (MEIM) and measures of their own and perceived friends’ substance use. Higher scores on the full scale MEIM indicating stronger cultural identity were found to be independently protective of Indigenous and Non-Indigenous alcohol initiation. More friends using substances was associated with increased substance use risk for both cultural groups. A factor analysis of the MEIM identified a two-factor structure, consisting of Affirmation/Belonging and Participation/Exploration. Few significant associations were found between the MEIM factors and cultural group substance use. Interactions between the MEIM factors and friends’ substance use indicated the two factors acted in the same way and decreased Non-Indigenous alcohol initiation for up to four drinking friends but were associated with risk for Indigenous alcohol initiation with any number of drinking friends.