bluuebunny/crossref_metadata_2025 huggingface dataset:
Second Asia–Pacific Consensus Guidelines for Helicobacter pylori infection
Authors: Fock K Ming , Katelaris Peter , Sugano Kentaro , Ang Tiing Leong , Hunt Richard , Talley Nicholas J , Lam Shiu Kum , Xiao Shu‐Dong , Tan Huck Joo , Wu Chun‐Ying , Jung Hyun Chae , Hoang Bui Huu , Kachintorn Udom , Goh Khean‐Lee , Chiba Tsutomu , Rani Abdul Aziz
Published: September 2009

The Asia–Pacific Consensus Conference was convened to review and synthesize the most current information on Helicobacter pylori management so as to update the previously published regional guidelines. The group recognized that in addition to long‐established indications, such as peptic ulcer disease, early mucosa‐associated lymphoid tissue (MALT) type lymphoma and family history of gastric cancer, H. pylori eradication was also indicated for H. pylori infected patients with functional dyspepsia, in those receiving long‐term maintenance proton pump inhibitor (PPI) for gastroesophageal reflux disease, and in cases of unexplained iron deficiency anemia or idiopathic thrombocytopenic purpura. In addition, a population ‘test and treat’ strategy for H. pylori infection in communities with high incidence of gastric cancer was considered to be an effective strategy for gastric cancer prevention. It was recommended that H. pylori infection should be tested for and eradicated prior to long‐term aspirin or non‐steroidal anti‐inflammatory drug therapy in patients at high risk for ulcers and ulcer‐related complications. In Asia, the currently recommended first‐line therapy for H. pylori infection is PPI‐based triple therapy with amoxicillin/metronidazole and clarithromycin for 7 days, while bismuth‐based quadruple therapy is an effective alternative. There appears to be an increasing rate of resistance to clarithromycin and metronidazole in parts of Asia, leading to reduced efficacy of PPI‐based triple therapy. There are insufficient data to recommend sequential therapy as an alternative first‐line therapy in Asia. Salvage therapies that can be used include: (i) standard triple therapy that has not been previously used; (ii) bismuth‐based quadruple therapy; (iii) levofloxacin‐based triple therapy; and (iv) rifabutin‐based triple therapy. Both CYP2C19 genetic polymorphisms and cigarette smoking can influence future H. pylori eradication rates.
Epidemiology of irritable bowel syndrome in Asia: Something old, something new, something borrowed
Authors: Gwee Kok‐Ann , Lu Ching‐Liang , Ghoshal Uday Chand
Published: September 2009

In this review we have unearthed epidemiological data that; support the ‘old’ concept of irritable bowel syndrome (IBS) as a disorder of civilization, build a ‘new’ symptom profile of IBS for Asia, and persuade us against the use of ‘borrowed’ Western diagnostic criteria and illness models by Asian societies. In the 1960s, IBS was described as a disorder of civilization. Early studies from Asia suggested a prevalence of IBS below 5%. Recent studies from Asia suggest a trend for the more affluent city states like Singapore and Tokyo, to have higher prevalence of 8.6% and 9.8%, respectively, while India had the lowest prevalence of 4.2%. Furthermore, there was a trend among the better educated and more affluent strata of society in several urban Chinese populations for a higher prevalence of IBS, as well as a trend for a higher consultation rate. Across Chinese and Indian predominant populations, a majority of patients with IBS criteria report upper abdominal symptoms such as epigastric pain relieved by defecation, bloating and dyspepsia. Bloating and incomplete evacuation appear to be more important determinants of consultation behavior, than psychological factors. The failure of the Rome criteria to recognize the relationship to meals, may have led to a substantial misclassification of IBS as dyspepsia. The relevance of the Western model of psychological disturbance as a determinant of consultation behavior is questionable because of the accessibility and acceptability of medical consultation for gastrointestinal complaints in many Asian communities.
Adiponectin knockout mice on high fat diet develop fibrosing steatohepatitis
Authors: Asano Takeharu , Watanabe Kiyotaka , Kubota Naoto , Gunji Toshiaki , Omata Masao , Kadowaki Takashi , Ohnishi Shin
Published: September 2009

Background and Aim:  Low levels of serum adiponectin have been reported to be associated with obesity, diabetes, and non‐alcoholic steatohepatitis (NASH), as well as several malignancies. Adiponectin knockout (KO) mice have been reported to cause insulin resistance and neointimal formation of the artery. We used adiponectin KO mice fed a high fat (HF) diet, and investigated the effect of adiponectin on the progression of steatohepatitis and carcinogenesis in vivo.

Methods:  Adiponectin KO mice and wild type (WT) mice were fed a HF diet or normal chow for the periods of 24 and 48 weeks. The HF diet contained 60% of calories from fat.

Results:  The adiponectin KO mice on the HF diet showed obesity, marked elevation of serum transaminase levels, and hyperlipidemia. At 24 weeks, hepatic expression of tumor necrosis factor‐α and procollagen α (I) was higher in KO mice as compared with WT mice. At 48 weeks, liver triglyceride contents in KO mice on normal chow were significantly higher than those in WT mice. Hepatocyte ballooning, spotty necrosis, and pericellular fibrosis around central veins were observed in KO mice on the HF diet. The pericellular fibrosis was more severe in KO mice on the HF diet than that in WT mice (1.62% vs 1.16%, P = 0.033). Liver adenoma and hyperplastic nodules developed in a KO mouse on the HF diet at 48 weeks (12.5%, n = 1/8), whereas no tumor was detected in WT mice (n = 10).

Conclusions:  Adiponectin may play a protective role in the progression of NASH in the early stages by suppressing tumor necrosis factor‐α expression and liver fibrosis.
Oral analgesia by non‐steroidal anti‐inflammatory drug zaltoprofen to manage cystoscopy‐related pain: A prospective study
Authors: Komiya Akira , Endo Takumi , Kobayashi Masayuki , Kim Woojin , Araki Kazuhiro , Naya Yukio , Suzuki Hiroyoshi , Tobe Toyofusa , Ichikawa Tomohiko , Fuse Hideki
Published: September 2009

Objectives:  To examine the pre‐emptive analgesic effect of the non‐steroidal anti‐inflammatory drug zaltoprofen against rigid cystoscopy‐associated pain, and compare it with the effect of an anesthetic gel.

Methods:  Forty men periodically undergoing follow‐up office cystoscopy were enrolled in this prospective study. The effects of lidocaine gel alone or in combination with zaltoprofen, were examined. The following parameters were assessed using an 11‐point numerical rating scale: pain during injection of gel into the urethra, insertion of rigid cystoscope, and the endoscopic examination of the urinary bladder, pain at the first urination after cystoscopy, and at the first urination in the following morning at home.

Results:  Pain scores with pre‐emptive zaltoprofen plus lidocaine gel were significantly lower than the ones with lidocaine gel alone at the time points of inserting rigid cystoscope into the urethra, viewing inside the urinary bladder and the first urination after cystoscopy. The efficacy of zaltoprofen was more significant in the patients with higher baseline pain score. There was no correlation between pain scores and bladder cancer grading, number of tumors, and time from surgery.

Conclusions:  Pre‐emptive zaltoprofen is able to control cystoscopy‐associated pain, which translates into better quality of life for patients. Thus, its use is recommended in the management of these patients.
How can structured self‐management patient education improve outcomes in people with type 2 diabetes?
Authors: Jarvis J. , Skinner T. C. , Carey M. E. , Davies M. J.
Published: September 2009

Type 2 diabetes (T2DM) is a long‐term chronic condition that is complex to manage, with the majority of management being done by the person with diabetes outside of the clinical setting. Because of its complexities, effective self‐management requires skills, confidence and the ability to make decisions and choices about treatments and lifestyle on a day‐to‐day basis. Equipping a person with these self‐management skills is in itself challenging and it is now widely accepted that structured education is an integral part of the management of T2DM. This paper explores whether structured self‐management education can improve outcomes in people with diabetes. The authors explore what self‐management education is, why it is needed and then go on to examine the recent evidence from clinical trials from 2006 onwards.
Managing women with gestational diabetes mellitus in the postnatal period
Authors: Kim Catherine
Published: September 2009

Guidelines for management of women with a history of gestational diabetes mellitus (GDM) in the postpregnancy period have lagged behind the recognition that this is an important time for medical intervention. However, in the past decade, the evidence‐base for screening algorithms, contraceptive management, diabetes prevention strategies and implications for offspring has expanded. In this review, we discuss current recommendations for managing women with GDM in the postnatal period, with particular attention to postpartum diabetes screening, prevention of future glucose intolerance and family planning.
Individual transferable quotas and ecosystem‐based fisheries management: it’s all in the T
Authors: Gibbs Mark T.
Published: September 2009

Recent articles in high‐profile journals advocating the widespread establishment of economic rights‐based approaches for managing fisheries has re‐kindled the debate over the efficacy of incentive‐based vs. regulatory‐based management approaches. Inspection of these works, written from the particular perspectives of economics, fisheries biology, or marine ecology, reveals that advocates of rights‐based regimes such as Individual Transferrable Quotas are sometimes recommending these policy instruments for quite different reasons. Hence, the advantageous attributes of rights‐based approaches from the perspective of one discipline may be quite different when seen from the perspective of another discipline. This is of concern as it exposes a tendency for particular disciplines to consider only the advantages of rights‐based approaches, such as establishing a harvest cap, but to implicitly discount the disadvantages such as less attention being paid to critical ecological and ecosystem issues.
THE TEN COMMANDMENTS FOR MANAGING VALUE AT RISK UNDER THE BASEL II ACCORD
Authors: Jiménez‐Martín Juan‐Ángel , McAleer Michael , Pérez‐Amaral Teodosio
Published: September 2009

Abstract Under the Basel II Accord, banks and other authorized deposit‐taking institutions are required to communicate their daily market risk estimates to the relevant national monetary authority at the beginning of each trading day, using one of a variety of value‐at‐risk (VaR) models to measure risk. The purpose of this paper is to provide a simple explanation and a set of prescriptions for managing VaR under the Basel II Accord. The commandments deal with understanding the Basel II colours, understanding the risk model before choosing, varying the choice of risk model, avoiding the green zone and being willing to violate, incurring large violations, stopping before the red zone, avoiding frequent violations, avoiding the estimation of large portfolios, aggregating portfolios into a single index and interpreting commandments sensibly as guidelines.
PRICE‐LEVEL TARGETING AND STABILISATION POLICY: A SURVEY
Authors: Ambler Steve
Published: September 2009

Abstract This paper surveys recent articles on the costs and benefits of price‐level targeting, focusing its use as a tool for stabilisation policy. It discusses how price‐level targeting can affect the short‐run trade‐off between output and inflation variability by influencing inflation expectations. It reviews how assigning an explicit price‐level target to a central bank that is unable to commit to its future policies can improve economic performance. It surveys other potential benefits and costs. Among the costs, it underlines the importance of perfectly rational expectations for the optimality of price‐level targeting, and an exacerbation of the time inconsistency problem.
HYSTERESIS IN UNEMPLOYMENT REVISITED: EVIDENCE FROM PANEL LM UNIT ROOT TESTS WITH HETEROGENEOUS STRUCTURAL BREAKS
Authors: Lee Jun‐De , Lee Chien‐Chiang , Chang Chun‐Ping
Published: September 2009

This paper applies the panel LM unit root tests with heterogeneous structural breaks in level by Im et al. (Oxford Bulletin of Economics and Statistics, 67 (2005), pp. 393–419) to re‐examine the validity of hysteresis in the unemployment rates of 19 OECD countries. Our empirical findings are favourable to the stationarity of the unemployment rates, i.e., the unemployment hysteresis hypothesis is strongly rejected. Our results suggest that shocks to unemployment rates are temporary and soon converge when we control for breaks. A major policy implication of the study is that a fiscal or monetary stabilization policy would not have permanent effects on the unemployment rates of the 19 OECD countries.
HEALTH IMPROVEMENTS AND THE TRANSITION OUT OF MALTHUSIAN STAGNATION
Authors: Currais Luis , Rivera Berta , Rungo Paolo
Published: September 2009

The central component of most economic models that analyse the transition from the Malthusian regime to self‐sustaining developed economies is education. Improved health is normally envisaged as simply a by‐product of economic growth. Whereas growth does, indeed, tend to improve health status, the reverse is also true, namely that health improvements are a dynamic force capable of driving economic expansion. This paper underlines the importance of health improvements in escaping from Malthusian stagnation. Further, and in contrast to existing literature, which emphasizes the effects of changes in mortality rates, this paper focuses on the relationship between health status and the efficiency of human capital technology. Through this channel, health improvements stimulate investments in child quality in terms of both nourishing and schooling and drive the economy towards the Modern Growth regime.
TRAFFIC MANAGEMENT IN WHOLESALE INTERNATIONAL ROAMING: TOWARDS A MORE EFFICIENT MARKET?*
Authors: Lupi Paolo , Manenti Fabio M.
Published: September 2009

Despite a general trend of lower charges for mobile calls, in Europe, prices for international roaming calls have remained at levels that are surprisingly high. The apparent reluctance of mobile network operators to lower roaming tariff is generating many antitrust concerns. This paper presents in a two‐country two‐firm framework the functioning of the current system governing wholesale international roaming agreements based on interoperator tariffs. The focus is on the role of traffic management; thanks to the emergence of traffic direction techniques, mobile network operators are allowed to select the roaming partner. We show that, unless these techniques do not allow for perfect control on traffic flows, traffic management does not improve the market's efficiency. In line with the regulatory mechanism recently adopted by the European Commission, we show that a simple price cap mechanism may restore partial efficiency in the wholesale market. We also show that although cross‐border cooperation at the wholesale level is Pareto efficient, it will not emerge as an equilibrium of a two‐sided matching game.
Interactive Graphics for Computer Adaptive Testing
Authors: Cheng I. , Basu A.
Published: September 2009

Interactive graphics are commonly used in games and have been shown to be successful in attracting the general audience. Instead of computer games, animations, cartoons, and videos being used only for entertainment, there is now an interest in using interactive graphics for ‘innovative testing’. Rather than traditional pen‐and‐paper tests, audio, video and graphics are being conceived as alternative means for more effective testing in the future. In this paper, we review some examples of graphics item types for testing. As well, we outline how games can be used to interactively test concepts; discuss designing chemistry item types with interactive 3D graphics; suggest approaches for automatically adjusting difficulty level in interactive graphics based questions; and propose strategies for giving partial marks for incorrect answers. We study how to test different cognitive skills, such as music, using multimedia interfaces; and also evaluate the effectiveness of our model. Methods for estimating difficulty level of a mathematical item type using Item Response Theory (IRT) and a molecule construction item type using Graph Edit Distance are discussed. Evaluation of the graphics item types through extensive testing on some students is described. We also outline the application of using interactive graphics over cell phones. All of the graphics item types used in this paper are developed by members of our research group.
Autostereoscopic Rendering of Multiple Light Fields
Authors: Escrivá M. , Blasco J. , Abad F. , Camahort E. , Vivó R.
Published: September 2009

Light fields were introduced a decade ago as a new high‐dimensional graphics rendering model. However, they have not been thoroughly used because their applications are very specific and their storage requirements are too high. Recently, spatial imaging devices have been related to light fields. These devices allow several users to see three‐dimensional (3D) images without using glasses or other intrusive elements.

This paper presents a light‐field model that can be rendered in an autostereoscopic spatial device. The model is viewpoint‐independent and supports continuous multiresolution, foveal rendering, and integrating multiple light fields and geometric models in the same scene.

We also show that it is possible to examine interactively a scene composed of several light fields and geometric models. Visibility is taken care of by the algorithm. Our goal is to apply our models to 3D TV and spatial imaging.
Log‐density Deconvolution by Wavelet Thresholding
Authors: BIGOT JÉRÉMIE , BELLEGEM SÉBASTIEN VAN
Published: September 2009

Abstract.  This paper proposes a new wavelet‐based method for deconvolving a density. The estimator combines the ideas of non‐linear wavelet thresholding with periodized Meyer wavelets and estimation by information projection. It is guaranteed to be in the class of density functions, in particular it is positive everywhere by construction. The asymptotic optimality of the estimator is established in terms of the rate of convergence of the Kullback–Leibler discrepancy over Besov classes. Finite sample properties are investigated in detail, and show the excellent empirical performance of the estimator, compared with other recently introduced estimators.
Adaptive Posterior Mode Estimation of a Sparse Sequence for Model Selection
Authors: SARDY SYLVAIN
Published: September 2009

Abstract.  For the problem of estimating a sparse sequence of coefficients of a parametric or non‐parametric generalized linear model, posterior mode estimation with a Subbotin(λ,ν) prior achieves thresholding and therefore model selection when ν  ∈   [0,1] for a class of likelihood functions. The proposed estimator also offers a continuum between the (forward/backward) best subset estimator (ν = 0), its approximate convexification called lasso (ν = 1) and ridge regression (ν = 2). Rather than fixing ν, selecting the two hyperparameters λ and ν adds flexibility for a better fit, provided both are well selected from the data. Considering first the canonical Gaussian model, we generalize the Stein unbiased risk estimate, SURE(λ,ν), to the situation where the thresholding function is not almost differentiable (i.e. ν  1). We then propose a more general selection of λ and ν by deriving an information criterion that can be employed for instance for the lasso or wavelet smoothing. We investigate some asymptotic properties in parametric and non‐parametric settings. Simulations and applications to real data show excellent performance.
Spectral Analysis of an Operator Arising in Fluid Dynamics
Authors: Chugunova Marina , Volkmer Hans
Published: September 2009

Eigenmode solutions are very important in stability analysis of dynamical systems. The set of eigenvalues of a non‐self‐adjoint differential operator originated from the linearization of some Cauchy problem is investigated. It is shown that the eigenvalues are purely imaginary, and that they are related to the eigenvalues of Heun's differential equation. These two results are used to derive the asymptotic behavior of the eigenvalues and to compute them numerically.
Risk factors for HIV transmission among heterosexual discordant couples in South India*
Authors: Kumarasamy N , Venkatesh KK , Srikrishnan AK , Prasad L , Balakrishnan P , Thamburaj E , Sharma J , Solomon S , Mayer K
Published: September 2009

Objective

To assess the risk factors associated with heterosexual HIV transmission among South Indian discordant couples enrolled in clinical care.

Methods

A nested matched case–control study of serodiscordant couples in which the HIV‐infected partner (index case) was enrolled in care. Demographic and clinical characteristics, sexual behaviours, CD4 cell count and plasma HIV‐1 RNA loads were measured at enrolment and longitudinally over 12 months of follow‐up. The study included 70 cases who seroconverted during study follow‐up and 167 matched controls who remained persistently serodiscordant.

Results

The incidence of HIV infection among the initially seronegative partners was 6.52 per 100 person‐years. Persistently discordant patients were more likely to have initiated highly active antiretroviral therapy (HAART) than patients in seroconverting relationships (62.9%vs. 42.9%) (P=0.001). Patients in seroconverting relationships had significantly higher plasma viral loads (PVLs) than patients in discordant relationships at enrolment, at 6 months and at 12 months (P<0.05). Patients in seroconverting relationships were less likely to use condoms with their primary partners than patients in discordant relationships (P<0.05). Patients in relationships that seroconverted between 6 and 12 months were diagnosed more often with genital Herpes simplex than patients in discordant relationships (P=0.001). In the univariate and multivariate logistic regression, the following variables were associated with seroconversion: PVL >100 000 [odds ratio (OR): 1.82; 95% confidence interval (CI): 1.1–2.8], non‐disclosure of HIV status (OR: 5.5; 95% CI: 4.3–6.2) and not using condoms (OR: 2.8; 95% CI: 2.4–3.6).

Conclusions

Couples‐based intervention models are crucial in preventing HIV transmission to seronegative spouses. Providing early treatment for sexually transmitted infections, HAART and enhancing condom use and disclosure could potentially decrease the risk of HIV transmission within Indian married couples.
Large particle hyaluronic acid for the treatment of facial lipoatrophy in HIV‐positive patients: 3‐year follow‐up study
Authors: Skeie L , Bugge H , Negaard A , Bergersen BM
Published: September 2009

Objectives

Facial lipoatrophy can be a stigmatizing side effect of antiretroviral (AVR) treatment for HIV‐infected patients. We sought to evaluate the long‐term efficacy and safety of a new formulation of hyaluronic acid that can be injected in larger amounts and into deeper skin layers during 3 years of follow‐up.

Methods

Twenty patients received injections of Restylane SubQ™. Refill treatment was offered at 12 and 24 months. Treatment effects were evaluated using ultrasound, the Global Aesthetic Improvement Scale, visual analogue scale (VAS) and the Rosenberg self‐esteem scale.

Results

Seventeen patients remained at 36 months. Mean (± standard deviation) total cutaneous thickness increased from 6 ± 1 mm at baseline to 12 ± 1 mm (P<0.001) at 36 months. Response rate (total cutaneous thickness >10 mm) was 70%. Fifteen patients classified their facial appearance as very much or moderately improved. VAS increased from 39 ± 25 to 70 ± 20 (P<0.05) and higher self‐esteem scores were reported. Local swelling and tenderness after treatment was common. Persistent papules found in several patients after treatment were removed effectively with hyaluronidase injections. Three patients, treated only at baseline, still had higher total cutaneous thickness scores at 36 months.

Conclusions

Our results indicate that a large particle hyaluronic acid formulation is a durable and well‐tolerated dermal filler for treating HIV‐positive patients with facial lipoatrophy.
Endothelial protein C receptor is expressed in rat cortical and hippocampal neurons and is necessary for protective effect of activated protein C at glutamate excitotoxicity
Authors: Gorbacheva Lyubov , Davidova Olga , Sokolova Elena , Ishiwata Shin’ichi , Pinelis Vsevolod , Strukova Svetlana , Reiser Georg
Published: September 2009

Activated protein C (APC) is an anticoagulant and anti‐inflammatory factor that acts via endothelial protein C receptor (EPCR). Interestingly, APC also exhibits neuroprotective activities. In the present study, we demonstrate for the first time expression of EPCR, the receptor for APC, in rat cortical and hippocampal neurons. Moreover, exposing the neurons to glutamate excitotoxicity we studied the functional consequence of the expression of EPCR. By cytotoxicity assay we showed that EPCR was necessary for the APC‐mediated protective effect in both neuronal cell types in culture. The effect of APC was abrogated in the presence of blocking EPCR antibodies. Analysis of neuronal death by cell labelling with dyes which allow distinguishing living and dead cells confirmed that the anti‐apoptotic effect of APC was dependent on both EPCR and protease‐activated receptor‐1. Thus, we suggest that binding of APC to EPCR on neurons and subsequent activation of protease‐activated receptor‐1 by the complex of APC‐EPCR promotes survival mechanisms after exposure of neurons to damaging factors.
Pre‐breeding diet influences ornament size in the Rhinoceros Auklet Cerorhinca monocerata
Authors: SORENSEN MARJORIE C. , HIPFNER J. MARK , KYSER T. KURT , NORRIS D. RYAN
Published: September 2009

Understanding the mechanisms that influence variation in sexually selected ornaments in seabirds has been challenging owing to the difficulty of capturing and sampling individuals outside of the breeding period when ornaments are usually grown. Stable carbon (δ13C) and nitrogen (δ15N) isotopes were used to examine the influence of pre‐breeding diet composition on ornament size in the Rhinoceros Auklet Cerorhinca monocerata, a socially monogamous seabird that breeds in the North Pacific. We analysed stable isotopes in adult feathers grown during the pre‐alternate moult, which allowed us to infer diet composition during the pre‐breeding (February–March) period. Females that fed more on inshore fish had larger horns than females that fed more on euphausiids (also known as krill; Euphausiacea). Body size was a stronger predictor of horn height in males than females, suggesting that ornaments may serve as different signals for each sex. This study provides evidence that diet during the pre‐breeding period can influence ornament size and emphasizes the importance of understanding individual ecology throughout the annual cycle for determining the factors that influence mate choice and fitness.
Oral bioavailability and brain penetration of (−)‐stepholidine, a tetrahydroprotoberberine agonist at dopamine D1 and antagonist at D2 receptors, in rats
Authors: Sun Yan , Dai Jieyu , Hu Zheyi , Du Feifei , Niu Wei , Wang Fengqing , Liu Fei , Jin Guozhang , Li Chuan
Published: September 2009

Background and purpose:  (−)‐Stepholidine has high affinity for dopamine D1 and D2 receptors. The aims of the present study were to examine the oral bioavailability and brain penetration of (−)‐stepholidine and to gain understanding of mechanisms governing its transport across the enterohepatic barrier and the blood–brain barrier.

Experimental approach:  The pharmacokinetics of (−)‐stepholidine was studied in rats and microdialysis was used to measure delivery to the brain. These studies were supported by biological measurement of unbound (−)‐stepholidine. Membrane permeability was assessed using Caco‐2 cell monolayers. Metabolite profiling of (−)‐stepholidine in rat bile and plasma was performed. Finally, in vitro metabolic stability and metabolite profile of (−)‐stepholidine were examined to compare species similarities and differences between rats and humans.

Key results:  Orally administered (−)‐stepholidine was rapidly absorbed from the gastrointestinal tract; two plasma concentration peaks were seen, and the second peak might result from enterohepatic circulation. Due to extensive pre‐systemic metabolism, the oral bioavailability of (−)‐stepholidine was poor (<2%). However, the compound was extensively transported across the blood–brain barrier, demonstrating an AUC (area under concentration–time curve) ratio of brain : plasma of ∼0.7. (−)‐Stepholidine showed good membrane permeability that was unaffected by P‐glycoprotein and multidrug resistance‐associated protein 2. In vitro (−)‐stepholidine was metabolized predominantly by glucuronidation and sulphation in rats and humans, but oxidation of this substrate was very low.

Conclusions and implications:  Although (−)‐stepholidine exhibits good brain penetration, future development efforts should aim at improving its oral bioavailability by protecting against pre‐systemic glucuronidation or sulphation. In this regard, prodrug approaches may be useful.
Differential activation of the HCO3‐conductance through the cystic fibrosis transmembrane conductance regulator anion channel by genistein and forskolin in murine duodenum
Authors: Tuo Biguang , Wen Guorong , Seidler Ursula
Published: September 2009

Background and purpose: Many cystic fibrosis (CF)‐associated mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channels affect CFTR‐activated HCO3‐transport more than Cl‐transport. Targeting the CFTR HCO3‐conductance, if possible, may therefore be of major therapeutic benefit. In the present study, we examined the effects of genistein and forskolin on duodenal mucosal HCO3‐and Cl‐secretion.

Experimental approach: Murine duodenal mucosal HCO3‐and Cl‐secretions were examinedin vitroin Ussing chambers by the pH stat and short circuit current (Isc) techniques.

Key results: Genistein markedly stimulated duodenal HCO3‐secretion andIscin a dose‐dependent manner in CFTR wild‐type mice, but not in CFTR null mice. CFTRinh‐172, a highly specific CFTR inhibitor, inhibited genistein‐stimulated duodenal HCO3‐secretion andIscin wild‐type mice. Genistein induced 59% net HCO3‐increase and 123% netIscincrease over basal value, whereas forskolin, an activator of adenylate cyclase, induced 94% net HCO3‐increase and 507% netIscincrease, indicating that, compared with forskolin, genistein induced a relatively high HCO3‐/Iscratio. Further data showed that CFTR HCO3‐/Cl‐conductance ratio was 1.05 after genistein stimulation, whereas after forskolin stimulation, the CFTR HCO3‐/Cl‐conductance ratio was 0.27.

Conclusions and implications: Genistein stimulates duodenal HCO3‐and Cl‐secretion through CFTR, and has a relatively high selectivity for the CFTR HCO3‐conductance, compared with forskolin. This may indicate the feasibility of selective targeting of the HCO3‐conductance of the CFTR channels.
Restoration of a Terrestrialized Soak Lake of an Irish Raised Bog: Results of Field Experiments
Authors: Crushell Patrick H. , Smolders Alfons J. P. , Schouten Matthijs G. C. , Robroek Bjorn J. M. , van Wirdum Geert , Roelofs Jan G. M.
Published: September 2009

Soaks (areas of mesotrophic/minerotrophic vegetation within acid bog) add to the overall heterogeneity and biodiversity of raised bog landscapes due to the presence of flora and fauna communities not typically associated with acid bog systems. A field experiment was set up to investigate the potential to restore the minerotrophic and aquatic communities that previously occurred within a soak of an oceanic raised bog in Ireland, which has recently undergone acidification with the expansion of acid bog type vegetation. Three different treatments, control (intact sphagnaceous raft), permeable (sphagnaceous raft removed), and enclosed (sphagnaceous raft removed and plots isolated from surrounding surface water influence) were applied to a total of six plots (each measuring 4 × 4 m), each treatment consisting of two replicates. Within 3 years a sphagnaceous raft with similar vegetation to the surroundings had developed in both permeable plots, while aquatic communities similar to those that occurred at the site in the past had established within the enclosed pots. Our results show that with manipulation of local hydrology it is possible to recreate conditions suitable for aquatic plant communities that once characterized the site. The results also give an insight into the likely processes responsible for the initial terrestrialization of the entire soak over the past century. Application of the results in relation to the site and the widespread practice of restoring bog vegetation on degraded peatlands are discussed.
Analysis of Implantable Defibrillator Longevity Under Clinical Circumstances: Implications for Device Selection
Authors: KNOPS PAUL , THEUNS DOMINIC A. M. J. , RES JAN C. J. , JORDAENS LUC
Published: September 2009

Introduction: Information about implantable cardioverter‐defibrillator (ICD) longevity is mostly calculated from measurements under ideal laboratory conditions. However, little information about longevity under clinical circumstances is available. This survey gives an overview on ICD service times and generator replacements in a cohort of consecutive ICD patients.

Methods: Indications for replacement were classified as a normal end‐of‐service (EOS), premature EOS, system malfunction, infection and device advisory, or recall actions. From the premature and normal EOS group, longevity from single‐chamber (SC), dual‐chamber (DC), and cardiac resynchronization therapy defibrillator (CRT‐D), rate‐responsive (RR) settings, high output (HO) stimulation, and indication for ICD therapy was compared. Differences between brands were compared as well.

Results: In a total of 854 patients, 203 ICD replacements (165 patients) were recorded. Premature and normal EOS replacements consisted of 32 SC, 98 DC and 24 CRT‐D systems. Longevity was significantly longer in SC systems compared to DC and CRT‐D systems (54 ± 19 vs. 40 ± 17 and 42 ± 15 months; P = 0.008). Longevity between non‐RR (n = 143) and RR (n = 11) settings was not significantly different (43 ± 18 vs. 45 ± 13 months) as it also was not for HO versus non‐HO stimulation (43 ± 19 vs. 46 ± 17 months). Longevity of ICDs was not significantly different between primary and secondary prevention (42 ± 19 vs. 44 ± 18 months). The average longevity on account of a device‐based EOS message was 43 ± 18 months. Average longevity for Biotronik (BIO, n = 72) was 33 ± 10 months, for ELA Medical (ELA, n = 12) 44 ± 17 months, for Guidant (GDT, n = 36) 49 ± 12 months, for Medtronic (MDT, n = 29) 62 ± 22 months, and for St. Jude Medical (SJM, n = 5) 31 ± 9 months (P < 0.001).

Conclusion: SC ICD generators had a longer service time compared to DC and CRT‐D systems. No influence of indication for ICD therapy and HO stimulation on generator longevity was observed in this study. MDT ICDs had the longest service time.
Premature Ventricular Contractions Arising from the Intramural Ventricular Septum
Authors: YAMADA TAKUMI , OKADA TARO , MURAKAMI YOSHIMASA , YOSHIDA NAOKI , MUROHARA TOYOAKI , KAY G. NEAL
Published: September 2009

A 68‐year‐old man with symptomatic idiopathic premature ventricular contractions (PVCs) underwent electrophysiological testing. Radiofrequency catheter ablation was unsuccessful at the earliest endocardial ventricular activation site in the left coronary cusp. Epicardial mapping via the cardiac veins was then performed. Balloon‐occluded coronary sinus venography revealed the small branches of the anterior interventricular vein. Mapping with a microcatheter revealed the earliest ventricular activation and perfect pace map at the distal portion of the septal perforating branch, suggesting an intramural ventricular septal PVC origin. Catheter ablation was abandoned because of the inaccessibility of the ablation catheter to that site via the venous system.
Simplified Demonstration of Cavotricuspid Isthmus Block After Catheter Ablation in Patients After Mustard's Operation
Authors: BALAJI SESHADRI , STAJDUHAR KARL C. , ZARRAGA IGNATIUS G. , KRON JACK
Published: September 2009

Background: The Mustard operation is a complex atrial rerouting performed in patients with transposition of the great arteries (TGA). Cavotricuspid isthmus (CTI)‐dependent atrial flutter (AFL) is an important problem in these patients. While catheter ablation (CA) is successful, three‐dimensional (3D) mapping is necessary to prove block at the CTI. 3D mapping, however, requires baffle puncture. We tested a simplified concept to prove isthmus block after CA for AFL in Mustard patients.

Methods: During electrophysiology study, catheters were placed in the high and low systemic venous atrium (HSVA and LSVA) and in the low pulmonary venous atrium (LPVA). LPVA and then LSVA were paced while recording in the HSVA and the alternate site. While pacing from one low site, the time taken to activate the other low site and the HSVA was compared before and after successful ablation.

Results: Three patients with Mustard operation and AFL underwent successful CA. Involvement of the CTI in AFL was proved by entrainment mapping. AFL was terminated during ablation and no longer inducible after ablation in all. LSVA pacing showed LPVA activation preceded HSVA activation preablation and activation pattern reversal after ablation. Likewise, LPVA pacing showed LSVA activation preceding HSVA preablation with reversal after ablation.

Conclusion: This study provides a simple method to demonstrate bidirectional block at the CTI in patients with CTI‐based AFL after Mustard operation for TGA.
Effect of Segregating Impurities on the Grain‐Boundary Character Distribution of Magnesium Oxide
Authors: Papillon Francine , Rohrer Gregory S. , Wynblatt Paul
Published: September 2009

The grain‐boundary character distribution (GBCD) of undoped MgO has been measured and compared with samples containing small concentrations of Ca, Sr, Ba, and Y. Auger electron spectroscopy measurements of intergranular fracture surfaces verified that Ca, Ba, and Y segregated anisotropically to grain boundaries (GBs). The segregation of Sr was not detected. The GBCDs of Ca, Ba, and Y doped MgO have more GBs comprised of {100} planes than the undoped material and the fractional area of these planes was highest in the Ca‐containing samples. Sr impurities, on the other hand, have no measurable influence on the GBCD. The results demonstrate that GB plane distributions can be controlled through impurity additions.
Biting Through an Arteriovenous Hemodialysis Graft: An Unusual Method of Suicide
Authors: Charlot Aglae , DeRoux Stephen
Published: September 2009

Abstract:  Patients on long‐term hemodialysis often have multiple medical and social problems with associated psychological stress and depression. The suicide rate in this population is higher than the general population, and suicides have been reported following severing or disconnection of hemodialysis vascular access sites. We report a patient on chronic hemodialysis with a history of depression and suicidal ideation who bit into his forearm arteriovenous graft and exsanguinated.
Disruption of the reproductive behaviour of Scaphoideus titanus by playback of vibrational signals
Authors: Mazzoni Valerio , Lucchi Andrea , Čokl Andrej , Prešern Janez , Virant‐Doberlet Meta
Published: September 2009

Scaphoideus titanus Ball (Hemiptera: Cicadellidae: Deltocephalinae) is the vector of the grapevine disease Flavescence dorée. In S. titanus the male–female duet (MFD), based on species‐specific vibrational signals, is essential for successful copulation. The female reply within a duet is a single pulse that is coupled with the male pulse with constant latency. It has been shown that a rival male can interrupt an existing duet by emitting disruptive noise signals. We tested whether the reproductive behaviour of S. titanus can be disrupted by the playback of intra‐specific and synthesized vibrational signals. Tested males responded to the playback of an MFD with typical rivalry behaviour. Such behaviour includes silent search for a duetting female (satellite behaviour) and/or emission of disruptive signals. These signals were emitted either after exchange of male–female pulses or after two male pulses coupled by latency corresponding to the female response window. The onset of male disruptive signals overlapped with a female pulse. We suggest that the intruder’s disruptive signals can mask the female reply and confuse courting males. Playback of disruptive vibrational signals reduced the level of male calling and interrupted an established MFD that consequently resulted in a significantly reduced number of copulations. These results indicate that the vibrational communication channel is open to interference either from abiotic environmental noise or from signals produced by sexual competitors or heterospecifics. The present study also suggests that a detailed understanding of leafhopper behaviour is essential for trying new approaches in the development of more environmentally friendly control practices.
Oncogenic BRAF and the tumor suppressor IGFBP7 in the genesis of atypical spitzoid nevomelanocytic proliferations
Authors: Emley Andrew , Yang Shi , Wajapeyee Narendra , Green Michael R , Mahalingam Meera
Published: September 2009

Rare reports indicate that the frequency of BRAFV600E mutations is high in atypical Spitz nevi. The purpose of this study was to ascertain the utility of the RAF/RAS mutational status as a diagnostic adjunct in lesions with histologic features that deviate from a typical Spitz nevus and, to examine expression of Insulin growth factor binding protein 7 (IGFBP7), a tumor suppressor acting through autocrine/paracrine pathways to inhibit BRAF‐MEK‐ERK signaling, in the same. Genomic DNA for genotyping was isolated from 6 regular Spitz nevi and 14 atypical spitzoid nevomelanocytic proliferations (including 1 melanoma with spitzoid histomorphology). NRAS1, NRAS2 and KRAS were analyzed, in addition to BRAFV600E. A mutation in BRAFV600E was noted in only one case–that of a regular Spitz nevus. IGFBP7 expression appeared to be maintained in this case, but was absent in 7/17 cases, which included 5 atypical spitzoid nevomelanocytic proliferations. Lack of expression of IGFBP7 in atypical spitzoid nevomelanocytic proliferations with histologically concerning features but BRAF‐WT indicates that the evolutionary path in atypical spitzoid nevomelanocytic proliferations is genetically distinct from that of IGFBP7‐negative BRAF‐positive melanoma. From an oncogenic BRAF perspective, our findings suggest that the majority of ‘atypical’ spitzoid nevomelanocytic proliferations are probably no different from conventional Spitz nevi.

Emley A, Yang S, Wajapeyee N, Green MR, Mahalingam M. Oncogenic BRAF and the tumor suppressor IGFBP7 in the genesis of atypical spitzoid nevomelanocytic proliferations.
Expression of survivin and human telomerase reverse transcriptase in extramammary Paget's disease
Authors: Shan Shi‐Jun , Zhang Naiqin , Geng Shi‐Ling , Zhou Zhihai , Chen Xu , Nie Tingfen , Guo Zhe , Li Changping , Liu Quanzhong , Guo Ying , Wei Huachen , Chen Hong‐Duo
Published: September 2009

Background: Extramammary Paget's disease (EMPD) is a rare neoplasm of apocrine gland‐bearing skin. It is known that over‐expression of survivin and human telomerase reverse transcriptase (hTERT) correlates with malignancies. We investigated the expression of hTERT and survivin by Paget's cells and their role in the tissue invasion and recurrence of EMPD.

Method: Forty‐two patients were enrolled into the study. Expression of survivin and hTERT were analyzed by immunohistochemistry and in situ hybridization techniques. The variables including the expression level of survivin and hTERT, gender, age, lesion location, invasion level and number of surgeries were statistically analyzed using Fisher's exact test.

Results: Survivin was positively stained in 18 of 22 cases (81.8%), and hTERT in 18 of 29 cases (62.1%). Significantly higher level of survivin expression was detected in patients with multiple surgeries than those with single one (p = 0.0458). Expression of hTERT was significantly higher in the patients with micro‐invasive and invasive lesions than those with non‐invasive lesions (p = 0.0478).

Conclusions: Over‐expression of survivin and hTERT correlated strongly with recurrence and local invasion of EMPD lesions. EMPD has male gender predominance in Oriental population.

Shan S‐J, Zhang N, Geng S‐L, Zhou Z, Chen X, Nie T, Guo Z, Li C, Liu Q, Guo Y, Wei H, Chen H‐D. Expression of survivin and human telomerase reverse transcriptase in extramammary Paget's disease.
Hydrological connectivity in coastal inland systems: lessons from a Neotropical fish metacommunity
Authors: De Macedo‐Soares P. H. M. , Petry A. C. , Farjalla V. F. , Caramaschi E. P.
Published: September 2009

de Macedo‐Soares PHM, Petry AC, Farjalla VF, Caramaschi EP. Hydrological connectivity in coastal inland systems: lessons from a Neotropical fish metacommunity. Ecology of Freshwater Fish 2010: 19: 7–18. © 2009 John Wiley & Sons A/S

Abstract –  We assessed the influence of hydrological connectivity in structuring fish communities through seasonal samplings of environmental variables and fishes in a coastal lagoon and associated pools in the Restinga de Jurubatiba National Park, Brazil. Community structure attributes such as species richness, numerical density and biomass, Shannon–Wiener diversity index and evenness were compared between periods of the lowest and highest hydrological connectivity, while the environmental gradient and fish zonation were explored through ordination techniques. The greater hydrological connectivity established in the rainy season promoted the homogenisation of most environmental variables and fish species, which differed markedly from the arrangement observed in the dry season. Despite variation in fish species composition, community attributes showed non‐significant differences between the dry and rainy seasons. The patterns of composition and numerical density in pools were strongly influenced by local factors, especially salinity, dissolved oxygen, total phosphorous concentration and water colour in the dry season, in addition to total nitrogen concentration and depth in the rainy season. Comparable to the role played by flood pulses in river‐floodplain systems, the hydrological connectivity in these tropical coastal waterbodies seems to strongly influence fish community structure, and, therefore to determine regional biodiversity.