bluuebunny/crossref_metadata_2025 huggingface dataset:
What you learn is what you see: using eye movements to study infant cross‐situational word learning
Authors: Yu Chen , Smith Linda B.
Published: March 2010

Recent studies show that both adults and young children possess powerful statistical learning capabilities to solve the word‐to‐world mapping problem. However, the underlying mechanisms that make statistical learning possible and powerful are not yet known. With the goal of providing new insights into this issue, the research reported in this paper used an eye tracker to record the moment‐by‐moment eye movement data of 14‐month‐old babies in statistical learning tasks. Various measures are applied to such fine‐grained temporal data, such as looking duration and shift rate (the number of shifts in gaze from one visual object to the other) trial by trial, showing different eye movement patterns between strong and weak statistical learners. Moreover, an information‐theoretic measure is developed and applied to gaze data to quantify the degree of learning uncertainty trial by trial. Next, a simple associative statistical learning model is applied to eye movement data and these simulation results are compared with empirical results from young children, showing strong correlations between these two. This suggests that an associative learning mechanism with selective attention can provide a cognitively plausible model of cross‐situational statistical learning. The work represents the first steps in using eye movement data to infer underlying real‐time processes in statistical word learning.
Developing simulations in multi‐user virtual environments to enhance healthcare education
Authors: Rogers Luke
Published: March 2010

Computer‐based clinical simulations are a powerful teaching and learning tool because of their ability to expand healthcare students' clinical experience by providing practice‐based learning. Despite the benefits of traditional computer‐based clinical simulations, there are significant issues that arise when incorporating them into a flexible, co‐operative and collaborative learning environment. Unlike traditional technologies; immersive multi‐user virtual environments such as Second Life can incorporate comprehensive learning materials with effective learning strategies, allowing healthcare students to obtain a simulated clinical experience in an immersive social environment. The purpose of this research was to investigate how a simulation could be optimised in Second Life to encourage teamwork and collaborative problem solving based on the habits, experiences and perceptions of nursing students towards Second Life as a simulation platform. The research was conducted by placing groups of nursing students in separate locations and exposing them to a series of clinical simulation developed in Second Life. The simulation involved a series of problem‐based scenarios, which incorporated concepts of technical skills, patient interaction, teamwork and situational awareness. Using qualitative feedback from a series of evaluative case studies, the study determined good practices and issues involved with a virtual computer‐based clinical simulation. A common theme which emerged from this research, which is discussed in this paper, was the student's ability to work in an artificial social structure where they could actively co‐construct mental models of technical and interpersonal skills through experiencing human interaction in a computer‐based simulated environment.
Constructive multiple‐choice testing system
Authors: Park Jooyong
Published: March 2010

The newly developed computerized Constructive Multiple‐choice Testing system is introduced. The system combines short answer (SA) and multiple‐choice (MC) formats by asking examinees to respond to the same question twice, first in the SA format, and then in the MC format. This manipulation was employed to collect information about the two different formats with no significant increase in testing time. Two empirical studies were carried out to examine whether meaningful information can be obtained using this system. One hundred and twenty nine fifth grade students (11 years old) were tested on science in Study 1, and 82 college students were tested for grade in Study 2. In both studies, consistent with previous research, students attained higher score in the MC format, the correlation between the SA format and the MC format was high, and the item discrimination was higher in the SA format when compared with the MC format. The unique finding from this study is that there were some cases where students chose a wrong MC option, even though they typed in the correct answer for the SA part. Possible applications of the system are discussed.
Online or face‐to‐face? An experimental study of examiner training
Authors: Chamberlain Suzanne , Taylor Rachel
Published: March 2010

Thousands of examiners are employed to mark candidate scripts from the suite of public examinations offered to students during the compulsory and post‐compulsory schooling phases in England, Northern Ireland and Wales. All examiners undergo training to ensure that they interpret correctly, and apply consistently, the mark scheme for their particular paper. Traditionally this training has been delivered face‐to‐face, but several benefits of an online training environment have been identified. This paper outlines the findings of an experimental study designed to quantify and compare the effects of face‐to‐face and online training on experienced examiners’ marking reliability. A sample of 89 experienced examiners was randomly allocated to either a face‐to‐face or online training group. The participants marked 30 General Certificate of Secondary Education History scripts prior to receiving training and another 30 scripts following training. Two measures of reliability were calculated: marking accuracy (absolute mark differences) and consistency (rank order correlations). The findings suggest that both modes of training had comparable, statistically significant positive effects on examiners’ accuracy and consistency. The evidence indicates that online training may be an effective alternative to face‐to‐face training for the purposes of standardising examiners’ marking.
Long‐term follow‐up of patients with asymptomatic occlusion of the internal carotid artery with good and impaired cerebral vasomotor reactivity
Authors: Kimiagar I. , Bass A. , Rabey J. M. , Bornstein N. M. , Gur A. Y.
Published: March 2010

Background:  Cerebral hemodynamic status might be prognostic for either the symptomatic or asymptomatic course of carotid occlusive disease. It is determined by evaluating cerebral vasomotor reactivity (VMR). We assessed VMR in asymptomatic patients with total occlusion of the internal carotid artery (ICA) and followed them to evaluate the role of impaired VMR in predicting ischaemic stroke (IS).

Methods:  Thirty‐five patients (21 men, mean age ± SD 68 ± 7.5 years) with unilateral asymptomatic ICA occlusion were studied by transcranial Doppler and the Diamox test (intravenous 1.0 g acetazolamide) and followed for 48 months or until reaching the end‐points of IS, transient ischaemic attack, or vascular death. VMR% was evaluated by recording the percent differences in peak systolic blood flow velocities in each middle cerebral artery at baseline and after Diamox administration.

Results:  Based on VMR% calculations, 14 (40%) patients had good VMRs and 21 (60%) had impaired VMRs. The global annual risk of ipsilateral ischaemic events was 5.7%. The annual ipsilateral ischaemic event risk was 1.8% in patients with good VMRs, whilst it was 7.1% in patients with impaired VMRs. An impaired VMR was significantly correlated with ipsilateral IS (Kaplan–Meier log rank statistic, P = 0.04).

Conclusions:  Our results support the value of VMR assessment for identifying asymptomatic patients with carotid occlusion who belong to a high‐risk subgroup for IS. New trials using extracranial‐to‐intracranial bypass surgery in patients with asymptomatic ICA occlusion and impaired VMRs are warranted.
The Wildlife Picture Index: monitoring top trophic levels
Authors: O'Brien T. G. , Baillie J. E. M. , Krueger L. , Cuke M.
Published: March 2010

Although recent biodiversity loss has been compared with cataclysmic mass extinctions, we still possess few indicators that can assess the extent or location of biodiversity loss on a global scale. The Convention on Biological Diversity (CBD) has mandated development of indicators that can meet the needs of monitoring biodiversity by 2010. To date, many indicators rely on unwarranted assumptions, secondary data, expert opinion and retrospective time series. We present a new biodiversity indicator, the Wildlife Picture Index (WPI) that targets medium and large‐sized terrestrial birds and mammals in forested and savannah ecosystems that. The WPI is a composite indicator based on the geometric mean of relative occupancy estimates derived from camera trap sampling at a landscape scale. It has been designed to meet the needs of a CBD indicator while avoiding many of the pitfalls that characterize some CBD indicators. We present an example using 8 years of camera trap data from Bukit Barisan Selatan National Park, Indonesia to show that the WPI is capable of detecting changes in the rate of loss of biodiversity, a key requirement of a CBD indicator. We conclude that the WPI should be effective at monitoring top trophic levels in forest and savannah ecosystems using primary data and can fill the gap in knowledge about trends in tropical biodiversity.
Developmental homoplasy: convergence in cellular differentiation
Authors: Graham Anthony
Published: March 2010

There is an accumulating body of evidence that highlights the fact that one can identify convergence in programmes of cellular differentiation. That is, that a particular differentiated cell/tissue type can be generated via non‐identical paths. Convergence is also seen in evolution and here it is termed homoplasy, thus one could term convergence in cellular differentiation, developmental homoplasy. It is important to appreciate its existence as it can confound our understanding of cellular differentiation. In particular, it highlights the point that the analysis of cellular differentiation in one region of the body may not generate an understanding that is generally applicable. The existence of the phenomenon of developmental homoplasy may lie in the evolutionary history of developmental processes, which are assembled over phylogenetic time. Such convergence in cellular differentiation may also have significance for understanding disease state and disease repair.
A CONSUMER PRICE INDEX FOR SWEDEN, 1290–2008
Authors: EDVINSSON RODNEY , SöDERBERG JOHAN
Published: March 2010

This paper presents a Consumer Price Index for Sweden 1290–2008. Constructing an index that covers more than seven centuries poses conceptual and empirical problems, and demands some methodological innovations. For example, during numerous occasions the currency unit was changed, and in some periods multiple currencies were used at floating exchange rates relative to each other. This paper also presents two different price indices, one that mainly serves the purposes of estimating real prices and real wages, and another that provides a measure of inflation. While the former follows the main currency unit, the latter also takes into account that debased coins were devalued during recoinage.
Prevalence and associated factors of non‐alcoholic fatty liver disease in patients with type‐2 diabetes mellitus
Authors: Leite Nathalie C. , Salles Gil F. , Araujo Antonio L. E. , Villela‐Nogueira Cristiane A. , Cardoso Claudia R. L.
Published: March 2010

Background/Aims: Diabetic patients have an increased prevalence and severity of non‐alcoholic fatty liver disease (NAFLD). We aimed to investigate the prevalence and the factors associated with the presence of ultrasonographic NAFLD in type‐2 diabetic individuals.

Methods: In a cross‐sectional design study, 180 type‐2 diabetic patients were submitted to a complete clinical and laboratory evaluation and abdominal ultrasonography for NAFLD detection and grading. Statistical analysis included bivariate tests, analysis of variance (anova, for increasing severity of steatosis) and multivariate logistic regression.

Results: The prevalence of ultrasonographic NAFLD was 69.4% [95% confidence interval (CI): 58.3–82.7%]. Patients with NAFLD were more obese, had a higher waist circumference and serum triglyceride and alanine aminotransferase (ALT) levels than those without steatosis. Neither diabetic degenerative complication, nor glycaemic control was associated with liver steatosis. On multivariate analysis, a high serum triglycerides level [>2.82 mmol/L, odds ratio (OR): 3.7–4.1, 95% CI: 1.2–13.3] and a high‐normal ALT level (≥40 U/L, OR: 2.5–2.7, 95% CI: 1.2–5.9) were independently associated with hepatic steatosis, together with either the presence of obesity (OR: 7.1, 95% CI: 3.0–17.0) or of increased waist circumference (OR: 4.8, 95% CI: 1.9–12.2).

Conclusions: Type‐2 diabetic patients have a high prevalence of ultrasonographic NAFLD and its presence is associated with obesity, mainly abdominal, hypertriglyceridaemia and high‐normal ALT levels. Non‐alcoholic fatty liver disease in diabetic patients may develop and progress independent of the diabetes progression itself.
The effect  of  1  month  of  therapy with midodrine, octreotide‐LAR and albumin in refractory ascites: a pilot study
Authors: Tandon Puneeta , Tsuyuki Ross T. , Mitchell Lesley , Hoskinson Michael , Ma Mang M. , Wong Winnie W. , Mason Andrew L. , Gutfreund Klaus , Bain Vincent G.
Published: March 2010

Background: The pathogenesis of refractory ascites (RA) is linked to splanchnic vasodilation. We hypothesized that a combination of midodrine, octreotide long‐acting release (LAR) and albumin would result in increased natriuresis, better control of ascites and an improvement in renal function in patients with RA±Type 2 hepatorenal syndrome.

Methods: A prospective pilot study in patients with RA as defined by the International Ascites Club. Consecutive patients received an intramuscular injection of octreotide‐LAR, 50 g of albumin three times per week and midodrine titrated to increase the systolic blood pressure for 1 month.

Results: Ten patients with RA were enrolled and eight with complete data to 1 month post‐treatment were included in the analysis. There was no change in renal function but there was a trend towards a reduction in the volume of ascites removed by paracentesis (P=0.08) and a significant reduction in the plasma renin (P=0.01) and aldosterone concentrations (P=0.01). Interestingly, there was a transient worsening in the model for end‐stage liver disease (MELD) score (P=0.01). The deterioration in MELD was completely reversible after discontinuation of therapy.

Conclusions: To our knowledge, this is the first study of prolonged midodrine, octreotide and albumin therapy in RA. We observed a significant reduction in the plasma renin and aldosterone concentrations and a trend towards a reduction in the volume of ascites removed by paracentesis without an effect on renal function. The beneficial effects are at the expense of a reversible deterioration in the MELD score. Large controlled trials are needed before this therapy can be routinely recommended.
Differential vascular endothelial growth factor A protein expression between small hepatocellular carcinoma and cirrhosis correlates with serum vascular endothelial growth factor A and α‐fetoprotein
Authors: Ginanni Corradini Stefano , Morini Sergio , Liguori Francesca , Carotti Simone , Onetti Muda Andrea , Antonella Burza Maria , Siciliano Maria , Molinaro Antonio , Cantafora Alfredo , Blotta Ida , Merli Manuela , Berloco Pasquale , Rossi Massimo , Francesco Attili Adolfo , Gaudio Eugenio
Published: March 2010

Background/Aims: Drugs with antivascular endothelial growth factor A (anti‐VEGF‐A) action are under clinical evaluation with encouraging results in advanced hepatocellular carcinoma (HCC). The relative VEGF‐A protein expression in non‐advanced HCC and in the cirrhotic non‐tumoral tissue in the same patient, a variable that could be important for treatment efficacy, has been investigated with conflicting results, only using the cirrhotic tissue surrounding the neoplasm (CS).

Methods: We measured, for the first time, VEGF‐A expression in non‐advanced HCC and in the respective CS and cirrhotic tissue at a distance from the tumour (CD), in 24 patients who underwent liver transplantation.

Results: VEGF‐A protein was more expressed (P<0.05) in HCC than in CD, while no difference was found between HCC and CS. In HCC patients with a serum α‐fetoprotein (AFP) higher than 20 ng/ml, VEGF‐A protein expression in HCC was higher than in the corresponding CD in 83% of cases and AFP and serum VEGF‐A corrected for the platelet count positively correlated with the differential VEGF‐A protein expression between HCC and CD.

Conclusion: Our data provide a rationale for clinical trials involving anti‐VEGF‐A treatments in patients with non‐advanced HCC, and suggest that serum AFP and VEGF‐A are variables to be taken into account in these studies.
Clinical and histological impact of previous hepatitis B virus infection in patients with chronic hepatitis C
Authors: Carvalho‐Filho Roberto J. , De Lucca Schiavon Leonardo , Narciso‐Schiavon Janaína L. , Sampaio Juliana P. , Lanzoni Valéria P. , Gomes Ferraz Maria L. , Benedito Silva Antonio E.
Published: March 2010

Background:Recent reports suggest that hepatitis C virus (HCV) carriers with serological markers of prior hepatitis B virus (HBV) infection have more advanced liver fibrosis, irrespective of HBV‐DNA detection.

Aims:We sought to assess the prevalence and impact of previous HBV infection in patients with HCV chronic infection.

Methods:This cross‐sectional study included hepatitis B surface antigen‐ and human immunodeficiency virus‐negative subjects with positive HCV‐RNA. All patients had prior parenteral exposure as the probable source of HCV infection. Serum samples were tested for HBV‐DNA using a commercial assay. The METAVIR system was used for histological analysis.

Results:One‐hundred and eleven patients were evaluated. Thirty‐one out of 111 patients (28%) tested positive for antihepatitis B core antigen (anti‐HBc). HBV‐DNA was not detected in any sample. Anti‐HBc‐positive patients showed higher histological grading, staging and a higher fibrosis progression rate. By multivariate analysis, anti‐HBc‐positivity was predictive of moderate to severe activity [odds ratio (OR)=3.532;P=0.032] and significant hepatic fibrosis (OR=3.364;P=0.017). After approximately 20 years of infection, advanced liver fibrosis (F3/F4) can be expected in 13% of anti‐HBc‐negative subjects who acquired HCV before the age of 30 and in 57% of those anti‐HBc‐positive patients who were infected by HCV after 30 years of age (P<0.001).

Conclusion:Previous HBV infection is common among HCV carriers and may exert a negative impact on the natural history of HCV infection, independently of the presence of significant HBV replication.
Non‐alcoholic fatty liver disease prevalence among school‐aged children and adolescents in Iran and its association with biochemical and anthropometric measures
Authors: Alavian Seyed‐Moayed , Mohammad‐Alizadeh Amir‐Hooshang , Esna‐Ashari Farzaneh , Ardalan Gelayol , Hajarizadeh Behzad
Published: March 2010

Objective: To investigate the prevalence of non‐alcoholic fatty liver disease (NAFLD) as well as the determination of associated metabolic abnormalities in Iranian school‐aged children and adolescents.

Method: Data were obtained from 966 children aged 7–18 years in Iran by a cross‐sectional survey in 2007. These children were subjected to a complete anthropometric and laboratory measurement and abdominal ultrasonography for liver echogenicity and size. A questionnaire was also used to obtain information on demographical and medical history, dietary habit, alcohol consumption and cigarette smoking.

Results: Fatty liver was diagnosed by ultrasound in 7.1% of children. The prevalence of elevated alanine aminotransferase (ALT) was 1.8%. NAFLD was significantly more common in the older group (12.5 against 3.5%, P<0.0001). The odds ratios (OR) (95% confidence interval) for NAFLD in children having elevated ALT, high fasting insulin, total cholesterol, low density lipoprotein (LDL) cholesterol, triglyceride and insulin resistance (IR) were 10.9 (3.9–30.4), 2.8 (1.6–4.8), 2.8 (1.5–5.1), 2.8 (1.5–5.3), 2.5 (1.3–4.8) and 4.4 (1.6–12.3) respectively. Therefore, NAFLD was significantly associated with increasing age, ALT, fasting insulin, total cholesterol, LDL cholesterol, triglyceride and IR. In multiple logistic regression analysis, ALT (OR=1.2; P<0.01), total cholesterol (OR=1.01; P<0.01) and waist circumference (OR=1.14, P<0.0001) were independent metabolic factors predictive of NAFLD after adjustment for other variables.

Conclusion: There was a strong relationship between NAFLD and the abnormal metabolic variables in children. It will be very useful if children are assessed for variables such as waist circumference, fasting blood sugar, fasting insulin and serum lipid profile in order to screen those susceptible to NAFLD.
Association between combinations of glutathione‐S‐transferase M1, T1 and P1 genotypes and non‐alcoholic fatty liver disease
Authors: Hori Masaharu , Oniki Kentaro , Nakagawa Takehiro , Takata Keiji , Mihara Shuichi , Marubayashi Toru , Nakagawa Kazuko
Published: March 2010

Background/Aims: Glutathione‐S‐transferases (GSTs) play a crucial role in antioxidant defence mechanisms, by detoxifying xenobiotics and by inactivating endogenous byproducts of oxidative stress. Functional failure, as a sequel of an altered GST genotype, may thus aggravate non‐alcoholic fatty liver disease (NAFLD). This study investigated whether the GSTs genotypes could affect the risk for NAFLD.

Methods: A cross‐sectional case–control analysis included 253 Japanese participants in a health screening programme. The GSTM1 null, GSTT1 null and GSTP1 Ile105Val variant genotypes were determined as putative high‐risk genotypes.

Results: The incidence of NAFLD was 27.3%. The frequency of the GSTM1 null genotype was higher in NAFLD than in the control [adjusted odds ratio (OR), 2.00; 95% confidence intervals (CI), 1.01–3.95]. Moreover, any combination of two putative high‐risk genotypes exhibited a higher risk for NAFLD with an adjusted OR from 3.52 (95% CI, 1.08–11.43)–4.01 (95% CI, 1.28–12.56). However, the significance for the combination of GSTM1 null and GSTT1 null genotypes only remained after Bonferroni's correction. In addition, the risk for NAFLD increased as the number of high‐risk genotypes, and the OR among three high‐risk genotypes carriers was 9.67 (95% CI: 1.61–58.26).

Conclusion: This is the first report to show the impact of the GSTs genotypes on the development of NAFLD. This finding, which should be confirmed in further studies in larger populations, may help to develop a more targeted prevention programme at an early stage for subjects with an increased risk for NAFLD.
Non‐invasive assessment of liver fibrosis by stiffness measurement in patients with chronic hepatitis B
Authors: Marcellin Patrick , Ziol Marianne , Bedossa Pierre , Douvin Catherine , Poupon Raoul , De Lédinghen Victor , Beaugrand Michel
Published: March 2010

Background: The need for new non‐invasive tools to assess liver fibrosis in chronic liver diseases has been largely advocated. Liver stiffness measurement (LSM) using transient elastography (FibroScan®, Echosens™) has been shown to be correlated to liver fibrosis in various chronic liver diseases. This study aims to assess its diagnosis accuracy in patients with chronic hepatitis B.

Patients and methods: We prospectively enrolled 202 patients with chronic hepatitis B in a multicentre study. Patients underwent liver biopsy (LB) and LSM. METAVIR and Ishak liver fibrosis stages were assessed by two pathologists.

Results: LSM or LB was considered unreliable in 29 patients. Statistical analysis was conducted in 173 patients. LSM was significantly (P<0.001) correlated with METAVIR (r=0.65) and Ishak fibrosis stage (0.65). The area under receiver‐operating characteristic curves were 0.81 (95% confidence intervals, 0.73–0.86) for F≥2, 0.93 (0.88–0.96) for F≥3 and 0.93 (0.82–0.98) for F=4. Optimal LSM cut‐off values were 7.2 and 11.0 kPa for F≥2 and F=4, respectively, by maximizing the sum D of sensitivity and specificity, and 7.2 and 18.2 kPa by maximizing the diagnosis accuracy.

Conclusion: In conclusion, LSM appears to be reliable for detection of significant fibrosis or cirrhosis in HBV patients and cut‐off values are only slightly different from those observed in HCV patients.
Prevalence and virological features of occult hepatitis B virus infection in female sex workers who work uncontrolled in Turkey
Authors: Pinarbasi Binnur , Onel Derya , Cosan Fulya , Akyuz Filiz , Dirlik Nezihe , Cakaloglu Yilmaz , Badur Selim , Besisik Fatih , Demir Kadir , Okten Atilla , Kaymakoglu Sabahattin
Published: March 2010

Background: There is little information about the prevalence of occult hepatitis B virus infection (OHBVI). We have investigated the prevalence and virological features of OHBVI among female sex workers (FSWs) in Istanbul.

Methods: Hepatitis B surface antigen (HBsAg) was tested in FSWs who work uncontrolled and were admitted to Venereal Diseases Hospital. HBV DNA and anti‐HBs were investigated in all the HBsAg‐negative cases. Hepatitis B envelope (HBe) antigen, anti‐HBe, anti‐hepatitis B core (HBc) antigen, HBV genotype, S gene and precore (PC)/basic core promoter (BCP) mutations were determined in HBV DNA‐positive sera.

Results: Two hundred and eighty‐six volunteers were enrolled and 32.5% (n=93) of them had anti‐HBs positivity. HBV DNA (range 30–209 copy/ml) was positive in 11 anti‐HBs‐negative and two anti‐HBs‐positive cases. The prevalence of OHBVI was 4.5% (13/286). Anti‐HBc was positive in 77% (10/13) of those with OHBVI and anti‐HBe positivity was 53.8% (7/13). Only genotype D was present in all occult HBV‐infected cases. One PC (G1896A) and one BCP (T1762/A1764) mutation was found, but S gene mutation was not detected in any of the samples.

Conclusion: In this population, OHBVI may have a negligible role in the horizontal transmission because of a very low viral load, and PC and core promoter mutations are very rare.
Pretreatment alanine transaminase level may not be the most important predictor of HBeAg loss in the older patient
Authors: Lee Jung Il , Park Hyun Joo , Lee Jin Woo , Kim Young Soo , Jeong Seok , Lee Don Haeng , Kim Hyung Gil , Shin Yong Woon , Kwon Kye Sook
Published: March 2010

Background: Elevated pretreatment alanine aminotransferase (ALT) over two times the upper limit of normal reference range has been accepted as a marker for predicting HBeAg loss and an indicator for initiating antiviral therapy. Recently, several opinions argued that in patients aged over 40 years, the treatment should be started if they have elevated serum hepatitis B virus (HBV) DNA without elevated ALT. However, initiating treatment in these patients might be argued against by the concept that the rate of HBeAg loss depends on the pretreatment ALT.

Aim: This study was conducted to investigate the usefulness of pretreatment ALT in predicting HBeAg loss in patients aged over 40 years under lamivudine treatment.

Methods: We retrospectively analyzed 820 HBeAg‐positive patients treated with lamivudine. The patients with hepatocellular carcinoma at or after initiating the lamivudine treatment and patients with evident liver cirrhosis were excluded. Three hundred fifty‐five patients met the criteria and were divided into two groups: ≤40 years of age (Group 1) and >40 years of age (Group 2).

Results: Analysis using the Kaplan–Meier method and the log rank test showed that the cumulative rate of HBeAg loss was not different in the two groups. Multivariate modelling indicated that an elevated pretreatment ALT level was a predictor of HBeAg loss in Group 1 (P<0.05), whereas it failed to act as a predictor in Group 2.

Conclusion: Antiviral therapy might not need to be deferred until the ALT level increases in order to enhance the chance of HbeAg loss in HBV DNA‐(+) patients aged over 40 years.
Budd‐Chiari syndrome in Sweden: epidemiology, clinical characteristics and survival – an 18‐year experience
Authors: Rajani Rupesh , Melin Tor , Björnsson Einar , Broomé Ulrika , Sangfelt Per , Danielsson Åke , Gustavsson Anders , Grip Olof , Svensson Hans , Lööf Lars , Wallerstedt Sven , Almer Sven HC
Published: March 2010

Background: The exact incidence and prevalence of Budd‐Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival.

Aims: To investigate the epidemiology, clinical presentation and survival in patients with BCS.

Methods: Retrospective multicentre study in Sweden reviewing the medical records of all patients with BCS 1986–2003, identified from the computerised diagnosis database of 11 hospitals, including all university hospitals and liver transplantation centres.

Results: Forty‐three patients with BCS were identified, of whom nine (21%) had concomitant portal vein thrombosis. The mean age‐standardised incidence and prevalence rates in 1990–2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. Myeloproliferative disorders (38%), thrombophilic factors (31%) and oral contraceptives (30%) were common aetiological factors. Two or more risk factors were present in 44%. In 23%, no risk factor was evident. The median follow‐up time was 2.7 years. Seventy‐two percent were on anticoagulant therapy during follow‐up. Transjugular intrahepatic portosystemic shunting, surgical shunting procedures and liver transplantation were performed in 4, 6 and 18 patients respectively. Nineteen patients died. The overall transplantation‐free survival at 1, 5 and 10 years was 47, 28 and 17% respectively.

Conclusions: Budd‐Chiari syndrome is a rare disorder; the mean age‐standardised incidence and prevalence rates in Sweden in 1990–2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. The presence of a myeloproliferative disorder was a common aetiological factor in our cohort and about half of the patients had a multifactorial aetiology. The transplantation‐free survival was poor.
Integrin alpha V polymorphisms and haplotypes in a Korean population are associated with susceptibility to chronic hepatitis and hepatocellular carcinoma
Authors: Lee Seung Ku , Kim Min‐Ho , Cheong Jae Youn , Cho Sung Won , Yang Song‐Ju , Kwack KyuBum
Published: March 2010

Background/Aims: Integrins are cell surface receptors for extracellular matrix (ECM) proteins that initiate signalling pathways that modulate proliferation, survival, invasion or metastasis. Consequently, integrins are potential targets for the treatment of cancer. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in integrin αV (ITGAV) in a Korean population were associated with chronic hepatitis B virus (HBV) infection and HBV‐infected hepatocellular carcinoma (HCC).

Patients and Methods: Thirteen ITGAV SNPs in 111 cases of chronic HBV infection, 86 cases of HBV‐infected HCC and 107 cases of acute self‐limited HBV infection were genotyped using Illumina's Sentrix array matrix (SAM) chip.

Results: The ITGAV intron SNPs rs9333289 and rs11685758, the 3′‐untranslated region SNP rs1839123 and haplotype 3 (T–T–A) were associated with enhanced susceptibility to HBV‐infected HCC (OR=1.75–2.42; P=0.02–0.05), while the intron SNP rs2290083 was associated with both chronic infection and HBV‐infected HCC (OR=1.73–2.01; P=0.01–0.04). In addition, both rs2290083 and ht1 (C–C–G) were associated with the age at which chronic infection occurred, as determined by Cox relative hazard analysis (RH=1.39–1.62, P=0.04–0.01)

Conclusion: ITGAV SNPs and haplotypes may be genetic factors that increase the susceptibility of Koreans to chronic HBV infection and HBV‐infected HCC.
Hepatitis C virus infection enhances insulin resistance induced by visceral fat accumulation
Authors: Eguchi Yuichiro , Mizuta Toshihiko , Ishibashi Eriko , Kitajima Yoichiro , Oza Noriko , Nakashita Shunya , Hara Megumi , Iwane Shinji , Takahashi Hirokazu , Akiyama Takumi , Ario Keisuke , Kawaguchi Yasunori , Yasutake Tsutomu , Iwakiri Ryuichi , Ozaki Iwata , Hisatomi Akitaka , Eguchi Takahisa , Ono Naofumi , Fujimoto Kazuma
Published: March 2010

Background/Aims: To clarify the impact of visceral obesity on hepatitis C virus (HCV)‐infected patients, we examined the relationship between insulin resistance development and visceral fat accumulation.

Methods: We analyzed 87 HCV‐infected patients with mild fibrosis (stage 1 or 2) in comparison with 125 sex‐ and age‐matched patients with non‐alcoholic fatty liver disease (NAFLD). The degree of visceral fat area (VFA; cm2) at the umbilical level was measured by abdominal computed tomography and divided into two grades: no visceral obesity, VFA<100 and visceral obesity, VFA≥100. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA‐IR) and the quantitative insulin sensitivity check index (QUICKI). Pancreatic β‐cell function was evaluated by homeostasis model assessment of β‐cell function (HOMA‐β). Serum soluble tumour necrosis factor (TNF)‐receptors 1 and 2 and adiponectin were measured.

Results: Insulin resistance evaluated by HOMA‐IR and QUICKI was correlated with visceral fat accumulation, and was higher in HCV patients than in NAFLD patients with visceral obesity. HOMA‐β was higher in HCV patients than in NAFLD patients for each VFA grade. Serum‐soluble TNF‐receptors 1 and 2 were higher in HCV patients than in NAFLD patients with visceral obesity.

Conclusions: Hepatitis C virus infection is a risk factor for development of insulin resistance, particularly in patients with visceral obesity.
Phosphorylation of extracellular signal‐regulated kinase 1/2, p38 mitogen‐activated protein kinase and nuclear translocation of nuclear factor‐κB are involved in upregulation of matrix metalloproteinase‐9 by tumour necrosis factor‐α
Authors: Itatsu Keita , Sasaki Motoko , Harada Kenichi , Yamaguchi Junpei , Ikeda Hiroko , Sato Yasunori , Ohta Tetsuo , Sato Hiroshi , Nagino Masato , Nimura Yuji , Nakanuma Yasuni
Published: March 2010

Background: Upregulation of matrix metalloproteinase‐9 (MMP‐9) induced by tumour necrosis factor‐α (TNF‐α) is reportedly involved in a variety of non‐neoplastic and neoplastic diseases. In this study, we examined which signalling pathways are involved in TNF‐α‐induced MMP‐9 upregulation in cholangiocarcinoma (CC).

Methods: We used two CC cell lines: HuCCT‐1 and CCKS‐1.

Results: In an ex vivo study using HuCCT‐1 and CCKS‐1 cells, TNF‐α treatment induced MMP‐9 production and activation via interaction with TNF receptor‐1 (TNF‐R1) but not with TNF receptor‐2 (TNF‐R2), shown by zymography, and increased MMP‐9 promoter activity (luciferase assay). As for the signalling pathway, TNF‐α stimulation led to the phosphorylation of extracellular signal‐regulated kinase 1/2 (Erk1/2) and p38 mitogen‐activated protein kinase (p38MAPK) and translocation of nuclear factor κB (NF‐κB) (p65) into the nuclei. Inhibition studies using SB203580 (inhibitor of p38MAPK), U0126 (inhibitor of mitogen‐activated or extracellular signal‐regulated protein kinase 1/2) and MG132 (inhibitor of NF‐κB) showed that the phosphorylation of Erk1/2 and p38MAPK with activation of NF‐κB was closely related to MMP‐9 upregulation in both cell lines.

Conclusion: These data suggest that TNF‐α/TNF‐R1 interaction leads to the phosphorylation of Erk1/2 and p38MAPK and nuclear translocation of NF‐κB, which is closely associated with the production and activation of MMP‐9 in cultured CC cells of HuCTT‐1 and CCKS‐1. Upregulation of MMP‐9 with NF‐κB activation may be involved in the tumour invasion of CC.
Hepatic steatosis in patients with chronic hepatitis C virus genotype 2 or 3 does not affect viral response in patients treated with peginterferon α‐2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) for 16 or 24 weeks
Authors: Rodriguez‐Torres Maribel , Govindarajan Sugantha , Diago Moises , Morgan Thomas , Anand Bhupinderjit , Barange Karl , Suter Frank , Lin Amy , Hooper Gregory , Shiffman Mitchell
Published: March 2010

Background: Hepatic steatosis is common in patients infected with hepatitis C virus (HCV). The effect of steatosis on anti‐HCV therapy efficacy is unclear.

Methods: We studied host and viral factors associated with steatosis and the effect of steatosis on treatment efficacy using the database of a large prospective trial in patients with HCV genotypes 2 and 3.

Results: Out of 885 patients assessed for steatosis, a total of 614 patients or 69% had steatosis. Patients with genotype 3 were more likely to have steatosis than those with genotype 2 (79 vs. 59%, P<0.001). Using the logistic regression model, steatosis was associated with genotype 3 (P<0.0001), older age (P=0.0025), heavier weight (P<0.0001), higher HCV RNA (P<0.0001), and higher ALT levels (P=0.015). By univariate analysis, steatosis was associated with lower sustained virological response (SVR) in patients with genotype 3, but not in patients with genotype 2. When all factors associated with steatosis and SVR were evaluated by logistic regression analysis; genotype, age, bodyweight, histological diagnosis, ALT quotient, baseline HCV RNA and treatment duration were associated with the probability of SVR, but gender, race and steatosis were not. Further analysis showed that steatosis remained a non‐significant factor while baseline viral load was significantly associated with the probability of an SVR.

Conclusions: Steatosis did not influence the efficacy of treatment in our study population. Baseline viral load is a confounding factor, particularly in patients infected with genotype 3 and once baseline viral load was accounted for, the association between steatosis and SVR was not relevant.
Caveolin‐1 and Rac regulate endothelial capillary‐like tubular formation and fenestral contraction in sinusoidal endothelial cells
Authors: Yokomori Hiroaki , Oda Masaya , Yoshimura Kazunori , Nagai Toshihiro , Fujimaki Kayo , Watanabe Shuichi , Hibi Toshifumi
Published: March 2010

Background/Aims: Rho guanidine triphosphatases (GTPases) are major regulators of cell migration. We investigated the cytoskeleton and Rho GTPases during cell migration and morphogenesis processes in isolated rat liver sinusoidal endothelial cells (LSECs) cultured on Matrigel while stimulated by the vascular endothelial growth factor (VEGF).

Methods: To obtain primary monolayers, LSECs were cultured on Matrigel for 5–17 h with or without VEGF. Sinusoidal endothelial fenestrae (SEF) morphology was observed using scanning electron microscopy and transmission electron microscopy. RhoA, Rac1 and phosphorylated myosin light‐chain kinase, Rho‐binding domain of Rhotekin and the p21‐binding domain of p21‐activated protein kinase were analysed using Western blotting.

Results: The LSECs showed cellular protrusions and or cords of aligned cells resembling primitive capillary‐like structures, with SEF contraction. Time course analyses of Rac1 activation matched specific morphological changes. Rac1 activity increased progressively to 17 h in cells cultured without VEGF, but markedly increased at 7 h in the presence of VEGF. RhoA activity was slightly elevated at 5 h. The levels of endogenous caveolin‐1 (CAV‐1) expression increased in a time‐dependent manner, reaching a peak at 7 h. CAV‐1 expression occurred immediately before the formation of the capillary‐like tube. Moreover, treatment with VEGF regulated CAV‐1 expression in LSECs.

Conclusions: Spatial activation of Rac1 is involved in the formation of a capillary‐like tubular network accompanying SEF contraction in LSECs, implying that endothelial migration and adhesion are necessary for LSECs tubular formation in the liver. CAV‐1 might play an important positive role in the regulation of LSEC tubular formation.
Management of the Diabetic Patient with Advanced Chronic Kidney Disease
Authors: Alicic Radica Z. , Tuttle Katherine R.
Published: March 2010

Diabetic kidney disease (DKD) is the leading cause of end‐stage renal disease (ESRD), and one of the most prevalent microvascular complications of both type 1 and type 2 diabetes. Additionally, risk of death is increased at all stages of DKD. As early as the microalbuminuric stage, the death rate approaches 20% per year. Therefore, management strategies should address reducing risk of mortality as well as progression to ESRD. DKD is associated with multiple co‐morbidities including hypertension, dyslipidemia, cardiovascular disease, anemia, and bone and mineral metabolism disorders (BMD). Anemia and BMD often occur earlier in the course of DKD than with other forms of chronic kidney disease. Pharmacological and dietary management of hyperglycemia, hypertension, dyslipidemia, anemia, and BMD pose specific challenges in DKD. However, with heightened awareness of risks and a multifactorial management approach, the impact of DKD on micro‐ and macrovascular complications and death can be reduced.
Glycemic Control and Burnt‐Out Diabetes in ESRD
Authors: Kovesdy Csaba P. , Park Jong C. , Kalantar‐Zadeh Kamyar
Published: March 2010

Treatment of early diabetes mellitus, the most common cause of chronic kidney disease (CKD), may prevent or slow the progression of diabetic nephropathy and lower mortality and the incidence of cardiovascular disease in the general diabetic population and in patients with early stages of CKD. It is unclear whether glycemic control in patients with advanced CKD, including those with end‐stage renal disease (ESRD) who undergo maintenance dialysis treatment is beneficial. Aside from the uncertain benefits of treatment in ESRD, hypoglycemic interventions in this population are also complicated by the complex changes in glucose homeostasis related to decreased kidney function and to dialytic therapies, occasionally leading to spontaneous resolution of hyperglycemia and normalization of hemoglobin A1c levels, a condition which might be termed “burnt‐out diabetes.” Further difficulties in ESRD are posed by the complicated pharmacokinetics of antidiabetic medications and the serious flaws in our available diagnostic tools used for monitoring long‐term glycemic control. We review the physiology and pathophysiology of glucose homeostasis in advanced CKD and ESRD, the available antidiabetic medications and their specifics related to kidney function, and the diagnostic tools used to monitor the severity of hyperglycemia and the therapeutic effects of available treatments, along with their deficiencies in ESRD. We also review the concept of burnt‐out diabetes and summarize the findings of studies that examined outcomes related to glycemic control in diabetic ESRD patients, and emphasize areas in need of further research.
Characteristics of Elderly Patients with Diabetes and End‐Stage Renal Disease
Authors: Goldfarb‐Rumyantzev Alexander S. , Rout Preeti
Published: March 2010

Because of a combination of demographic and social factors, such as the aging of the population in general, increased incidence of diabetes, and more liberal criteria for renal replacement therapy initiation, the proportion of the end‐stage renal disease (ESRD) patients with diabetes who are considered elderly is currently the fastest growing segment of incident ESRD population. Despite the fast growth of this group, it is poorly characterized in current literature. In this review, we attempt to summarize the data available to date regarding demographic composition, outcomes, choice of renal replacement therapy, and other management issues including renal transplantation. There is significant evidence that the elderly diabetic patients might differ from the general dialysis population regarding renal replacement modality, vascular access for dialysis, and that guidelines addressing chronic kidney disease (CKD) issues such as nutrition and blood pressure may need modification in this ESRD subgroup. At the same time, other areas such as anemia and bone mineral metabolism have not been adequately studied. Lastly, despite lower rates of kidney transplantation in this population, it confers significant survival advantages, similar to that seen in younger populations. As the fastest growing group in the incident ESRD population, these patients have issues related to clinical management, which represent very important areas for future research.
Transplantation in Diabetic Kidney Failure Patients: Modalities, Outcomes, and Clinical Management
Authors: Luan Fu L. , Samaniego Millie
Published: March 2010

Diabetes mellitus (DM) is a common and devastating disease, affecting up to 19.3 million Americans. It is the leading cause of chronic kidney disease (CKD) and end‐stage renal disease (ESRD) in the United States. Diabetic patients with ESRD have a high incidence of cardiovascular disease and death. For those kidney transplant patients with no history of DM prior to transplantation, the development of new onset diabetes after transplantation (NODAT) also poses a serious threat to both graft and patient survival. Kidney transplantation is the best renal replacement option for diabetic ESRD and has the potential to halt the progression of cardiovascular diseases. Early referral for transplant evaluation is essential for pre‐emptive or early kidney transplantation in this cohort of patients. In type 1 DM patients with ESRD, simultaneous pancreas and kidney transplantation (SPK) should be encouraged; and in patients facing prolonged waiting time for SPK transplantation but with an available living donor, living donor kidney transplantation followed by pancreas after kidney transplantation (PAK) is a suitable alternative. Islet transplantation in type 1 diabetics is deemed experimental by Medicare, and easy access to this modality remains restricted to qualified patients enrolled in clinical trials or with private insurance. The optimal management of kidney transplant patients with pre‐existent DM or NODAT involves a multi‐pronged approach consisting of pharmacological and nonpharmacological intervention to address all potential cardiovascular risk factors such as glycemic and lipid control, blood pressure control, weight loss, and smoking cessation. Finally, re‐transplantation should be recommended in suitable kidney transplant patients when the kidney allograft demonstrates continuous and progressive decline in function.
Outcomes of Arteriovenous Fistulae Created by a U.S. Interventional Nephrologist
Authors: Mishler Rick , Yevzlin Alexander S.
Published: March 2010

Arteriovenous fistulae (AVF) outcomes in the United States continue to fall short of expectations and continue to compare disfavorably to European AVF outcomes. This study presents the early experience of nephrologist created AVF outcomes in the U.S. hemodialysis population. A retrospective analysis of a prospectively collected vascular access database was performed. All patients who were referred for vascular access placement over a 1‐year period were eligible for inclusion. One hundred five (n = 105) patients were initially included in the database. An AVF was placed in 100% of patients referred for vascular access. Two complications were identified (one steal syndrome and one infection) for a rate of 1.9%. The patient demographics included 38.7% female, age 63.6±14.8, 50.0% diabetic, 66.0% hypertensive, with 65.1% of patients in stage 5 chronic kidney disease at the time of AVF placement. Average target artery diameter was 4.09 ± 1.16 mm while average target vein diameter was 3.66 ± 1.20. Twenty‐one AVF were placed in the forearm (19.8%) with the remainder being placed in the upper arm vessels. Eighteen patients (18.56%) failed to mature at 6 weeks. Sixty‐four patients (65.98%) required revision or intervention of their AVF between 12 weeks postoperatively and the endpoint of the study. Eighty patients (84.21%) had patent AVF at an average follow‐up of 286.2 ± 98.14 days. No identifiable risk factors among those listed above were associated with a significant impact on AVF outcomes. AVF outcomes that compare favorably to those of Europe can be achieved by U.S. interventional nephrologists. Furthermore, the dictum that distal is better needs to be re‐examined if the United States hopes to achieve the goal of 66% AVF prevalence.