bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simulation Study of Control Sampling Methods for Nested Case-Control Studies of Genetic and Molecular Biomarkers and Prostate Cancer Progression
Authors: Wang Ming-Hsi , Shugart Yin Yao , Cole Stephen R. , Platz Elizabeth A.
Published: March 2009

Background: Incidence density sampling is typically the least biased efficient method for control sampling in nested case-control studies. However, in studies of genetic variants and prostate cancer progression, some argue that controls should be sampled from men who did not progress by end of follow-up. Thus, we examined the validity of relative risk (RR) estimates of prostate cancer progression using three methods for control sampling from cohorts of men with prostate cancer generated by Monte Carlo simulation.

Methods: Data were simulated for nine scenarios for combinations of genotype frequency (10%, 30%, and 50%) and association (RR, 1.0, 1.5, and 2.0) using prostate progression rates from Johns Hopkins Hospital. RRs estimated from conditional logistic regression for the genetic association from case-control studies nested in the nine cohort scenarios using three control sampling methods, (a) incidence density sampling, (b) incidence density sampling without replacement of selected controls, and (c) “pure” control sampling (i.e., men who did not progress by end of long-term follow-up), were compared with the true RRs.

Results: Use of controls selected by incidence density sampling produced unbiased RR estimates of progression. In our setting, only a slight bias was produced by use of incidence density sampling without replacement. In contrast, use of controls selected by pure control sampling produced biased RR estimates, except when there was no association; extent of bias increased with increasing size of the association and duration of follow-up.

Conclusions: Nested case-control studies designed to estimate the association of genetic variants with risk of prostate cancer progression should use incidence density sampling to provide a valid RR estimate. (Cancer Epidemiol Biomarkers Prev 2009;18(3):706–11)
Candidate Gene Analysis Using Imputed Genotypes: Cell Cycle Single-Nucleotide Polymorphisms and Ovarian Cancer Risk
Authors: Goode Ellen L. , Fridley Brooke L. , Vierkant Robert A. , Cunningham Julie M. , Phelan Catherine M. , Anderson Stephanie , Rider David N. , White Kristin L. , Pankratz V. Shane , Song Honglin , Hogdall Estrid , Kjaer Susanne K. , Whittemore Alice S. , DiCioccio Richard , Ramus Susan J. , Gayther Simon A. , Schildkraut Joellen M. , Pharaoh Paul P.D. , Sellers Thomas A.
Published: March 2009

Polymorphisms in genes critical to cell cycle control are outstanding candidates for association with ovarian cancer risk; numerous genes have been interrogated by multiple research groups using differing tagging single-nucleotide polymorphism (SNP) sets. To maximize information gleaned from existing genotype data, we conducted a combined analysis of five independent studies of invasive epithelial ovarian cancer. Up to 2,120 cases and 3,382 controls were genotyped in the course of two collaborations at a variety of SNPs in 11 cell cycle genes (CDKN2C, CDKN1A, CCND3, CCND1, CCND2, CDKN1B, CDK2, CDK4, RB1, CDKN2D, and CCNE1) and one gene region (CDKN2A-CDKN2B). Because of the semi-overlapping nature of the 123 assayed tagging SNPs, we performed multiple imputation based on fastPHASE using data from White non-Hispanic study participants and participants in the international HapMap Consortium and National Institute of Environmental Health Sciences SNPs Program. Logistic regression assuming a log-additive model was done on combined and imputed data. We observed strengthened signals in imputation-based analyses at several SNPs, particularly CDKN2A-CDKN2B rs3731239; CCND1 rs602652, rs3212879, rs649392, and rs3212891; CDK2 rs2069391, rs2069414, and rs17528736; and CCNE1 rs3218036. These results exemplify the utility of imputation in candidate gene studies and lend evidence to a role of cell cycle genes in ovarian cancer etiology, suggest a reduced set of SNPs to target in additional cases and controls. (Cancer Epidemiol Biomarkers Prev 2009;18(3):935–44)
Long-Term Dietary Acrylamide Intake and Risk of Epithelial Ovarian Cancer in a Prospective Cohort of Swedish Women
Authors: Larsson Susanna C. , Åkesson Agneta , Wolk Alicja
Published: March 2009

Background: Acrylamide, a probable human carcinogen, can be formed in carbohydrate-rich foods cooked at high temperatures. Whether dietary acrylamide intake is associated with the risk of cancer in humans is uncertain. We aimed to assess the relation between dietary acrylamide intake and the incidence of epithelial ovarian cancer.

Methods: The Swedish Mammography Cohort is a population-based prospective study of 61,057 Swedish women. Diet was assessed with a food-frequency questionnaire at baseline in 1987-1990 and again in 1997.

Results: During a mean follow-up of 17.5 years, we ascertained 368 incident cases of ovarian cancer. We observed no association between acrylamide intake and the risk of ovarian cancer. Compared with the lowest quartile of acrylamide intake (mean intake, 16.9 μg/day), the multivariable rate ratios for the highest quartile (mean intake, 32.5 μg/day) were 0.86 (95% confidence interval, 0.63-1.16) for total ovarian cancer and 1.05 (95% confidence interval, 0.68-1.63) for serous ovarian cancer (n = 182 cases).

Conclusions: The results from this prospective study provide no evidence that dietary acrylamide in amounts typically consumed by Swedish women is associated with the risk of ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(3):994–7)
CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis
Authors: Vasilatos Shauna N. , Broadwater Gloria , Barry William T. , Baker Joseph C. , Lem Siya , Dietze Eric C. , Bean Gregory R. , Bryson Andrew D. , Pilie Patrick G. , Goldenberg Vanessa , Skaar David , Paisie Carolyn , Torres-Hernandez Alejandro , Grant Tracey L. , Wilke Lee G. , Ibarra-Drendall Catherine , Ostrander Julie H. , D'Amato Nicholas C. , Zalles Carola , Jirtle Randy , Weaver Valerie M. , Seewaldt Victoria L.
Published: March 2009

Background: Only 5% of all breast cancers are the result of BRCA1/2 mutations. Methylation silencing of tumor suppressor genes is well described in sporadic breast cancer; however, its role in familial breast cancer is not known.

Methods: CpG island promoter methylation was tested in the initial random periareolar fine-needle aspiration sample from 109 asymptomatic women at high risk for breast cancer. Promoter methylation targets included RARB (M3 and M4), ESR1, INK4a/ARF, BRCA1, PRA, PRB, RASSF1A, HIN-1, and CRBP1.

Results: Although the overall frequency of CpG island promoter methylation events increased with age (P < 0.0001), no specific methylation event was associated with age. In contrast, CpG island methylation of RARB M4 (P = 0.051), INK4a/ARF (P = 0.042), HIN-1 (P = 0.044), and PRA (P = 0.032), as well as the overall frequency of methylation events (P = 0.004), was associated with abnormal Masood cytology. The association between promoter methylation and familial breast cancer was tested in 40 unaffected premenopausal women in our cohort who underwent BRCA1/2 mutation testing. Women with BRCA1/2 mutations had a low frequency of CpG island promoter methylation (15 of 15 women had ≤4 methylation events), whereas women without a mutation showed a high frequency of promoter methylation events (24 of 25 women had 5-8 methylation events; P < 0.0001). Of women with a BRCA1/2 mutation, none showed methylation of HIN-1 and only 1 of 15 women showed CpG island methylation of RARB M4, INK4a/ARF, or PRB promoters.

Conclusions: This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(3):901–14)
Reproductive Variables, Soy Intake, and Lung Cancer Risk among Nonsmoking Women in the Singapore Chinese Health Study
Authors: Seow Adeline , Koh Woon-Puay , Wang Renwei , Lee Hin-Peng , Yu Mimi C.
Published: March 2009

Lung cancer among nonsmokers has emerged as a distinct clinicopathologic entity for which the etiology is still poorly understood, but which accounts for a significant proportion of the lung cancers among women. Although estrogens have been shown to have mitogenic effects in lung cells and interact with growth factor pathways in tumorigenesis, epidemiologic evidence for a link between reproductive hormones and lung cancer is sparse and inconsistent. We examined the effect of parity, age at menarche/menopause, cycle length and use of exogenous hormones, and dietary soy and soy isoflavonoid intake on lung cancer risk in a prospective cohort of middle-aged and elderly Chinese women in Singapore among whom 91% were lifetime nonsmokers. Among 35,298 women (mean follow-up time, 9.6 years), 298 cases of incident lung cancer were recorded, of which 189 (63.4%) occurred in nonsmokers. Compared with nulliparous women, those with one to two, three to four, and more than five livebirths had relative risks of between 0.49 and 0.59 (P for trend < 0.01) for all lung cancers, and between 0.32 and 0.42 (P for trend < 0.001) for adenocarcinomas. This relationship was observed in both smokers and nonsmokers. Age at menarche and menopause did not seem to influence risk. Dietary soy isoflavonoid intake was associated with a statistically significant inverse trend among nonsmokers only (relative risks, 0.59 for highest versus lower quartile; P for trend, 0.021). These findings add support for the role of hormonal factors in the etiology of lung cancer among nonsmoking women, and are consistent with emerging experimental evidence in this regard. (Cancer Epidemiol Biomarkers Prev 2009;18(3):821–7)
DNA Promoter Methylation in Breast Tumors: No Association with Genetic Polymorphisms in MTHFR and MTR
Authors: Tao Meng Hua , Shields Peter G. , Nie Jing , Marian Catalin , Ambrosone Christine B. , McCann Susan E. , Platek Mary , Krishnan Shiva S. , Xie Bin , Edge Stephen B. , Winston Janet , Vito Dominica , Trevisan Maurizio , Freudenheim Jo L.
Published: March 2009

Aberrant promoter methylation is recognized as an important feature of breast carcinogenesis. We hypothesized that genetic variation of genes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR), two critical enzymes in the one-carbon metabolism, may alter DNA methylation levels and thus influence DNA methylation in breast cancer. We evaluated case-control association of MTHFR C677T, A1298C, and MTR A2756G polymorphisms for cases strata-defined by promoter methylation status for each of three genes, E-cadherin, p16, and RAR-β2 in breast cancer; in addition, we evaluated case-case comparisons of the likelihood of promoter methylation in relation to genotypes using a population-based case-control study conducted in Western New York State. Methylation was evaluated with real-time methylation-specific PCRs for 803 paraffin-embedded breast tumor tissues from women with primary, incident breast cancer. We applied unordered polytomous regression and unconditional logistic regression to derive adjusted odds ratios and 95% confidence intervals. We did not find any association of MTHFR and MTR polymorphisms with breast cancer risk stratified by methylation status nor between polymorphisms and likelihood of promoter methylation of any of the genes. There was no evidence of difference within strata defined by menopausal status, estrogen receptor status, folate intake, and lifetime alcohol consumption. Overall, we found no evidence that these common polymorphisms of the MTHFR and MTR genes are associated with promoter methylation of E-cadherin, p16, and RAR-β2 genes in breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(3):998–1002)
Obesity and Weight Gain in Adulthood and Telomere Length
Authors: Kim Sangmi , Parks Christine G. , DeRoo Lisa A. , Chen Honglei , Taylor Jack A. , Cawthon Richard M. , Sandler Dale P.
Published: March 2009

Obesity and weight gain in adulthood are associated with an increased risk of several cancers. Telomeres play a critical role in maintaining genomic integrity and may be involved in carcinogenesis. Using data from 647 women ages 35 to 74 years in the United States and Puerto Rico (2003-2004), we examined the association between current and past anthropometric characteristics and telomere length in blood. In a multivariate linear regression model, higher current body mass index (BMI) and hip circumference were inversely associated with telomere length. Higher BMI in the 30s was associated with shorter telomere length among women ages ≥40 years (Ptrend < 0.01). Weight gain since the age 30s (Ptrend = 0.07) and weight cycling (Ptrend = 0.04) were also inversely associated with telomere length. When current BMI and BMI at ages 30 to 39 years were considered together, the most marked decrease in telomere length was found for women who had overweight or obese BMI at both time points (mean telomere repeat copy number to single-copy gene copy number ratio = 1.26; 95% confidence interval, 1.21-1.30) compared with women who had normal BMI at both times (mean telomere repeat copy number to single-copy gene copy number ratio = 1.33; 95% confidence interval, 1.30-1.36). These findings support the hypothesis that obesity may accelerate aging, and highlight the importance of maintaining a desirable weight in adulthood. (Cancer Epidemiol Biomarkers Prev 2009;18(3):816–20)
Involuntary Tobacco Smoke Exposure and Urinary Levels of Polycyclic Aromatic Hydrocarbons in the United States, 1999 to 2002
Authors: Suwan-ampai Plernpit , Navas-Acien Ana , Strickland Paul T. , Agnew Jacqueline
Published: March 2009

Evidence supports active smoking as a major source of exposure to polycyclic aromatic hydrocarbons (PAH), compounds that are mutagenic and carcinogenic in humans. The influence of involuntary exposure to tobacco smoke on PAH exposure levels among nonsmokers, however, is unknown. This study evaluated the association between both active and involuntary tobacco smoke and biomarkers of PAH exposure in the general U.S. population. A cross-sectional analysis of 5,060 participants ≥6 years of age was done using data from the 1999-2002 National Health and Nutrition Examination Survey (NHANES). PAH exposure was measured by urinary concentrations of 23 monohydroxylated metabolites of nine PAH compounds. Tobacco smoke exposure was defined as no exposure, involuntary exposure, and active exposure by combining serum cotinine levels, smoking status, and presence of household smokers. PAH metabolite levels ranged from 33.9 ng/L for 9-hydroxyphenanthrene to 2,465.4 ng/L for 2-hydroxynaphthalene. After adjustment for age, sex, race/ethnicity, education, household income, and broiled/grilled food consumption, participants involuntarily and actively exposed to tobacco smoke had urinary metabolite concentrations that were increased by a factor of 1.1 to 1.4 and 1.5 to 6.9, respectively, compared with unexposed participants. Associations for involuntary smoking were stronger and statistically significant for 1-hydroxypyrene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, and 3-hydroxyphenanthrene compared with other metabolites. Involuntary exposure to tobacco smoke was associated with elevated urinary concentrations of most PAH metabolites in a representative sample of the U.S. population. Policy and educational efforts must continue to minimize PAH exposure through active and involuntary tobacco smoke exposure. (Cancer Epidemiol Biomarkers Prev 2009;18(3):884–93)
Etiologic Heterogeneity for Cervical Carcinoma by Histopathologic Type, Using Comparative Age-Period-Cohort Models
Authors: Reimers Laura L. , Anderson William F. , Rosenberg Philip S. , Henson Donald E. , Castle Philip E.
Published: March 2009

Background: Cervical carcinomas comprise two main histopathologic types, squamous cell carcinomas and adenocarcinomas. Human papillomavirus (HPV) infections are causative for both types but the respective tumors may have different carcinogenic pathways.

Methods: To assess potential etiologic heterogeneity of cervical cancer by histopathologic type, we examined invasive squamous cell carcinomas and adenocarcinoma cervical cancer incidence rates in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. We complemented standard descriptive epidemiology with comparative age-period-cohort (APC) models fitted to each histopathologic type.

Results: Squamous cell tumors (n = 25,219) were nearly 5-fold more common than adenocarcinomas (n = 5,451). Age-adjusted incidence trends decreased for squamous cell carcinomas but increased for adenocarcinomas. Cross-sectional age-specific incidence rates increased more rapidly for squamous cell carcinomas than adenocarcinomas in adolescents and young adults then leveled off for both types. APC models confirmed that secular trends and age-specific rates differed for the two types (P = 0 for the null hypothesis of no difference). For squamous cell carcinoma, the APC “fitted” age-at-onset rate curve peaked before age 40 years then declined; for adenocarcinoma, the fitted curve increased rapidly until age 40 years then rose more slowly.

Conclusions: Despite the necessary role of HPV infection in both squamous cell carcinomas and adenocarcinomas of the cervix, secular trends and age-related natural histories differed for the two tumor types, consistent with etiologic heterogeneity. Future analytic and clinical studies should consider the interaction (effect modification) of HPV infection and other cervical carcinoma risk factors by histopathologic type, time, and age. (Cancer Epidemiol Biomarkers Prev 2009;18(3):792–800)
Total and Unopposed Estrogen Exposure across Stages of the Transition to Menopause
Authors: O'Connor Kathleen A. , Ferrell Rebecca J. , Brindle Eleanor , Shofer Jane , Holman Darryl J. , Miller Rebecca C. , Schechter Deborah E. , Singer Burton , Weinstein Maxine
Published: March 2009

Detailed characterization of estrogen dynamics during the transition to menopause is an important step toward understanding its potential implications for reproductive cancers developing in the transition years. We conducted a 5-year prospective study of endogenous levels of total and unopposed estrogen. Participants (n = 108; ages 25-58 years) collected daily urine specimens for 6 months in each of 5 consecutive years. Specimens were assayed for estrone-3-glucuronide (E1G) and pregnanediol-3-glucuronide. Linear mixed-effects models were used to estimate exposure to total and unopposed estrogen by age and reproductive stage. Reproductive stage was estimated using menstrual cycle length variance. E1G mean area under the curve and mean E1G 5th and 95th percentiles represented total estrogen exposure. An algorithm identifying days of above-baseline E1G that coincided with the days of baseline pregnanediol-3-glucuronide was used to identify days of unopposed estrogen. Mean E1G area under the curve increased with age in the pretransition and early transition and decreased in the late transition. Ninety-fifth percentile E1G levels did not decline until after menopause, whereas 5th percentile levels declined from the early transition to the postmenopause. The number of days of unopposed estrogen was significantly higher during the transition compared with the pretransition. Given the length of time women spend in the transition, they are exposed to more total and unopposed estrogen than has been previously appreciated. Coupled with epidemiologic evidence on lifetime exposure to estrogen, these results suggest that variation in the amount of time spent in the transition may be an important risk factor for reproductive cancers. (Cancer Epidemiol Biomarkers Prev 2009;18(3):828–36)
Longitudinal Cognitive Decline in Subcortical Ischemic Vascular Disease – The LADIS Study
Authors: Jokinen Hanna , Kalska Hely , Ylikoski Raija , Madureira Sofia , Verdelho Ana , van der Flier Wiesje M. , Scheltens Philip , Barkhof Frederik , Visser Marieke C. , Fazekas Franz , Schmidt Reinhold , O’Brien John , Waldemar Gunhild , Wallin Anders , Chabriat Hugues , Pantoni Leonardo , Inzitari Domenico , Erkinjuntti Timo
Published: March 2009

Background: Cross-sectional studies have indicated that subcortical ischemic vascular disease (SIVD), as defined according to imaging criteria, is associated with a specific clinical and cognitive profile. Much less is known about the long-term cognitive consequences of SIVD. The aim of the study was to investigate the longitudinal cognitive performance and incident dementia in subjects with and without SIVD in a sample of older adults with white matter lesions. Methods: In the Leukoaraiosis and Disability (LADIS) study, 639 participants were examined with annual clinical and neuropsychological evaluations for 3 years. The subjects meeting the MRI criteria of SIVD at baseline were compared to the other subjects of the sample with linear mixed models. Results: The overall level of cognitive performance over the follow-up period was inferior in multiple cognitive domains in SIVD subjects as compared to the reference group. The subjects with SIVD presented significantly steeper decline of performance in the Stroop test (parts I and II), Trail Making A test, Verbal fluency test, and Mini-Mental State Examination. They also had a threefold risk of developing dementia during follow-up independently of age, sex, education and medial temporal lobe atrophy. Conclusions: SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk of developing dementia. SIVD seems to specifically contribute to the deterioration of psychomotor speed, executive control, and global cognitive function.
The Effect of Recent Consumption of Caffeine-Containing Foodstuffs on Neuropsychological Tests in the Elderly
Authors: Lesk Valerie E. , Honey Thurza E.M. , de Jager Celeste A.
Published: March 2009

We investigated the effect of recent intake of caffeine-containing foodstuffs (CCFS) on a group of elderly participants (age range 67–95 years) on a series of neuropsychological tests. There was no significant effect of CCFS intake on performance in any of the tests in the battery used. However, a significant interaction effect was found between age and CCFS consumption on scores of some neuropsychological tests. In these tests, participants with recent consumption of CCFS show a linear decrease in performance with increasing age, a pattern not seen for those that have no CCFS in their system. Accuracy in the neuropsychological assessment is of great importance when determining whether someone has a cognitive impairment or early Alzheimer’s disease. We therefore propose that recent consumption of CCFS should be taken into account when scoring the neuropsychological assessment.
Adenosine A1 Receptors Determine Glomerular Hyperfiltration and the Salt Paradox in Early Streptozotocin Diabetes Mellitus
Authors: Vallon Volker , Schroth Jana , Satriano Joseph , Blantz Roland C. , Thomson Scott C. , Rieg Timo
Published: March 2009

Background: In early type 1 diabetes mellitus, changes in proximal reabsorption influence glomerular filtration rate (GFR) through tubuloglomerular feedback (TGF). Due to TGF, a primary increase in proximal reabsorption causes early diabetic hyperfiltration, while a heightened sensitivity of the proximal tubule to dietary salt leads to the so-called salt paradox, where a change in dietary salt causes a reciprocal change in GFR (‘tubulocentric principle’). Here, experiments were performed in adenosine A1 receptor knockout mice (A1R–/–), which lack an immediate TGF response, to determine whether A1Rs are essential for early diabetic hyperfiltration and the salt paradox. Methods: GFR was measured by inulin disappearance in conscious A1R–/– and wild-type (WT) mice after 4 weeks of streptozotocin diabetes on a control NaCl diet (1%), and measurements were repeated after 6 days of equilibration on a low-NaCl (0.1%) or a high-NaCl (4%) diet. Results: A1R–/– and WT were similar with respect to blood glucose, dietary intakes and body weight changes on a given diet. Diabetic hyperfiltration occurred in WT, but was blunted in A1R–/–. A reciprocal relationship between GFR and dietary salt was found in WT diabetics, but not A1R–/– diabetics or nondiabetics of either strain. Conclusion: A1Rs determine glomerular hyperfiltration and the salt paradox in early diabetes, which is consistent with the tubulocentric principle.
The mediating effect of job satisfaction and organizational commitment on self-reported performance: more robust evidence of the PSM—performance relationship
Authors: Vandenabeele Wouter
Published: March 2009

Public service motivation (PSM) has been linked to various outcome variables, but as more and more public administration research is devoted to improving performance, the possible link between PSM and performance is increasingly of interest. The current study contributes to this literature by investigating whether this relationship is present in a dataset of Belgian civil servants. The results corroborate the general thesis and demonstrate a mediation effect (to some extent) of job satisfaction and organizational commitment on this relationship. By doing so, the present study partly unveils the mechanisms upon which the PSM—performance relationship is based.

Points for practitioners The findings of this study should urge public managers and decision-makers to value the effect of PSM in a public sector environment. First, as individual PSM apparently correlates with performance, this might provide some ideas about how to manage human resources in an effectiveness and efficiency driven public sector. Considering PSM in recruitment, retention and training may engender better individual performance. Next to this, the mediating role of job satisfaction and organizational commitment should enable public managers to find more openings to harness PSM effectively. After all, it embeds PSM better into vested theory and practices, with which practitioners may be more familiar.
How to fully exploit the results of e-government user surveys: the case of Slovenia
Authors: Kunstelj Mateja , Jukić Tina , Vintar Mirko
Published: March 2009

The article presents users' views on the development of e-government, addressing two interrelated questions that have not been sufficiently answered thus far: (1) How to increase the current low level of e-government use, and (2) How to advance the current practice of analyzing data from e-government satisfaction surveys in order to arrive at guidelines for decision-makers when shaping future actions of e-government development. For this purpose, a cause-and-effect model was developed and operationalized by a set of indicators observed by a citizen satisfaction survey carried out in Slovenia between 2005 and 2006. The model was then estimated using the PLS (Partial Least Squares) regression method. Finally, an improvement-priority matrix was applied to prioritize significant factors. The proposed manner of analyzing data from user surveys offers a universal tool for analyzing drivers and consequences of user satisfaction and the use of e-government, and prioritizing them in order to assist decision-makers in preparing future strategies, action plans, or guidelines for further developments.

Points for practitioners

1. Methodological implications:

• guidelines on how to conduct e-government user satisfaction surveys;

• guidelines on how to analyze user survey data in order to formulate guidelines for future development of e-government.

2. Empirical implications:

•results of e-government user satisfaction survey in Slovenia and other countries;

• guidelines for future development of e-government services in Slovenia and beyond.
Welfare Spending in an Era of Globalization: The North—South Divide
Authors: Glenn John
Published: March 2009

This paper examines the assertion that economic globalization has led to the decline of welfare spending in recent decades. Although it is often argued that the increasing intensity of globalization has led to such a decline in the industrialized states, the paper finds that there has been little, if any, downturn in either levels of state expenditure in general or in levels of welfare spending in particular. However, the experience of the developing states has been rather different. In their case, the last few decades indicate that stagnation or a decline in welfare spending has occurred, particularly during the period of structural adjustment implementation. It is argued that the OECD countries still manage to provide a high level of social welfare to their populations that closely resembles the compensatory state model. In contradistinction, many of the states in the South have struggled to maintain their levels of social expenditure and therefore most resemble Cerny's competitive state model. In order to explain these two divergent outcomes, the paper examines the way in which the behaviour of certain key international financial actors (investors, multinational companies, international financial institutions) differs with regard to these two sets of countries.
Roundtable: The Limits of Bridge-Building
Authors: Kurki Milja , Stavrianakis Anna , Klabbers Jan , Eschle Catherine , Maiguashca Bice , Grovogui Siba N.
Published: March 2009

This roundtable develops arguments presented at the 2008 International Studies Association (ISA) annual convention. The theme of the convention was `Bridging Multiple Divides' and its aim to enhance dialogue among the diverse research communities within international studies. The aim of the `Limits of Bridge-Building' panel at ISA, and the present roundtable, has been to probe the challenges presented by bridge-building and specifically the possible limitations or dangers that might inhere within attempts to build bridges in International Relations. The roundtable then is aimed at problematising the concept of bridge-building and sounding a hesitant note that takes seriously not only the possibilities but also the limitations and, indeed, possible dangers of `bridge-building'.
When the working day is through: the end of work as identity?
Authors: Doherty Michael
Published: March 2009

This article seeks to present a counter-case to the `end of work thesis' advocated by writers such as Beck et al. It argues that work remains a significant locus of personal identity and that the depiction by these writers of endemic insecurity in the workplace is inaccurate and lacks empirical basis. The article draws upon case study data to illustrate how, across a range of workplaces, work remains an importance source of identity, meaning and social affiliation.
Identity work and the `unemployed' worker: age, disability and the lived experience of the older unemployed
Authors: Riach Kathleen , Loretto Wendy
Published: March 2009

This article seeks to explore how older individuals negotiate and manage their self-identity in relation to work while situated without paid employment. After reviewing the current positions of the older unemployed in the UK, noting the substantial overlap between age and disability, we turn our attention to conceptualizing the lived experiences of individuals through exploring `identity work' as a means of understanding a non-working work identity. Based upon focus group interviews, our empirical analysis focuses on key dimensions of participants' identity practice and how they sought to manage the following social processes: imposed identities; crafting working identities; and contesting unfavourable working identities.The conclusion contextualizes the findings against a backdrop of increasing individualistic discourses underpinning approaches to employability, closes with the policy implications arising from this study, and makes suggestions for future research agendas.
Before the disaster: health, safety and working conditions at a plastics factory
Authors: Taylor Phil , Connelly Laurence
Published: March 2009

On 11 May 2004, nine workers were killed and forty injured in an explosion which devastated the Grovepark Mills plant in Glasgow of ICL Plastics Ltd.This was the worst health and safety incident in Scotland since Piper Alpha in 1988 and the most serious on the Scottish mainland since the 1960s.The narrative presented is that of Laurence Connelly, a production worker with 14 years' service, who left the company only weeks before the disaster. Generated over a series of interviews as part of an independent study of the incident, Laurence's testimony depicts a seriously flawed health and safety regime that left workers exposed to a range of hazards, and recallsTheo Nichols' characterisation of such workplaces as constituting `potentially injurious structure[s] of vulnerability'. It raises questions about the efficacy of regulatory bodies including the UK's Health and Safety Executive and how such workplaces and whistleblowers within them are treated.
Intermediate occupations and the conceptual and empirical limitations of the hourglass economy thesis
Authors: Anderson Pauline
Published: March 2009

It is suggested that an hourglass-shaped occupational structure is emerging in the UK, with the polarization of jobs at top and bottom of the occupational hierarchy. Despite the implicit suggestion that jobs in the middle appear to be disappearing, somewhat paradoxically, there are ever-increasing reports of problems with recruitment and skill across intermediate occupations.This article attempts to address the paradox and propose better ways of conceptualizing what is happening to intermediate occupations within recent structural transformations. It is argued that while the hourglass economy thesis, or a variation of it, best describes recent occupational transformations, it is limited conceptually and empirically. More specifically, it neglects important dimensions of change within intermediate occupations — dimensions that may well provide a more fruitful foundation from which to explore the nature of and developments within these jobs and their broader repercussions.
Early toxic effects of fumonisin B1 in rat liver
Authors: Domijan AM , Želježić D , Peraica M , Kovačević G , Gregorović G , Krstanac Ž , Horvatin K , Kalafatić M
Published: March 2009

Mycotoxin fumonisin B1 (FB1) is hepatotoxic and carcinogenic in experimental animals. It is known that long-term exposure of experimental animals to FB1 causes apoptosis and lipid peroxidation. In this study, male adult Wistar rats were treated with single FB1 doses (5, 50, and 500 μg/kg b.w.) and sacrificed 4, 24, and 48 hours after treatment. Parameters of oxidative stress, histopathological changes, and DNA damage were monitored in the liver of treated and control animals. Parameters of oxidative stress were not affected by such treatment. A significant increase in apoptotic cells appeared in animals when 5 μg/kg b.w. dose was given and sacrificed after 24 hours with further increase at higher doses. In contrast to the number of mitotic figures and karyomegaly seen mostly at lower FB1 doses, necrosis was the prominent feature at higher doses. Significant increase in liver cells DNA mobility was observed 48 hours following treatment with 50 and 500 μg/kg b.w. as compared to control (tail length 15.2 ± 0.3, 16.4 ± 0.5, and 13.5 ± 0.1 μm, respectively). Tail intensity appeared to be more sensitive parameter for detecting DNA damage even at 5 μg/kg b.w. after 48 hours (1.69 ± 0.27% DNA; control 0.59 ± 0.11% DNA). This study proved that FB1-induced DNA damage is time- and dose-dependent, and that it could be caused in Wistar rats by a single dose.
Transcriptional changes in U343 MG-a glioblastoma cell line exposed to ionizing radiation
Authors: Bassi CL , Mello SS , Cardoso RS , Godoy PDV , Fachin AL , Junta CM , Sandrin-Garcia P , Carlotti CG , Falcão RP , Donadi EA , Passos GAS , Sakamoto-Hojo ET
Published: March 2009

Glioblastoma multiforme (GBM) is a highly invasive and radioresistant brain tumor. Aiming to study how glioma cells respond to γ-rays in terms of biological processes involved in cellular responses, we performed experiments at cellular context and gene expression analysis in U343-MG-a GBM cells irradiated with 1 Gy and collected at 6 h post-irradiation. The survival rate was approximately 61% for 1 Gy and was completely reduced at 16 Gy. By performing the microarray technique, 859 cDNA clones were analyzed. The Significance Analysis of Microarray algorithm indicated 196 significant expressed genes (false discovery rate (FDR) = 0.42%): 67 down-regulated and 97 up-regulated genes, which belong to several classes: metabolism, adhesion/cytoskeleton, signal transduction, cell cycle/apoptosis, membrane transport, DNA repair/DNA damage signaling, transcription factor, intracellular signaling, and RNA processing. Differential expression patterns of five selected genes ( HSPA9B, INPP5A, PIP5K1A, FANCG, and TPP2) observed by the microarray analysis were further confirmed by the quantitative real time RT-PCR method, which demonstrated an up-regulation status of those genes. These results indicate a broad spectrum of biological processes (which may reflect the radio-resistance of U343 cells) that were altered in irradiated glioma cells, so as to guarantee cell survival.
Protection of cyclophosphamide-induced toxicity in reproductive tract histology, sperm characteristics, and DNA damage by an herbal source; evidence for role of free-radical toxic stress
Authors: Rezvanfar MA , Sadrkhanlou RA , Ahmadi A , Shojaei-Sadee H , Rezvanfar MA , Mohammadirad A , Salehnia A , Abdollahi M
Published: March 2009

Cyclophosphamide (CP) as an anticancer alkylating agent has been known as a male reproductive tract toxicant. The aim of this study was to examine whether Satureja khuzestanica essential oil (SKEO) as an established herbal antioxidant, might protect tract rat reproductive system from toxicity of CP. To reach this aim, total antioxidant power (TAP) and lipid peroxidation (LPO) in testis and plasma, blood levels of sex hormones, sperm characteristics, DNA integrity and chromatin quality, and fertility in male rats were tested. Histopathological analysis of testes and epididymides and staining of mast cells were performed for assessment of spermatogenic disorders. CP (6 mg/kg/day) and SKEO (225 mg/kg/day) were administered alone or in combination by gavage for 28 days. In the CP-exposed rats, testicular and plasma LPO increased, TAP decreased, plasma testosterone diminished, and both spermatogenesis and fertility were impaired. In CP-treated rats, a decrease in sperm quality was associated with increased DNA damage and decreased chromatin quality. Coadministration of SKEO significantly improved CP-induced changes in plasma testosterone, sperm quality, spermatogenesis and fertility, toxic stress, and DNA damage. It is concluded that CP-induced toxic effects on androgenesis and spermatogenesis is mediated by free radicals. SKEO protects reproductive system from toxicity of CP through its antioxidant potential and androgenic activity.
Learning Mazes with Aliasing States: An LCS Algorithm with Associative Perception
Authors: Zatuchna Zhanna V. , Bagnall Anthony
Published: March 2009

Learning classifier systems (LCSs) belong to a class of algorithms based on the principle of self-organization and have frequently been applied to the task of solving mazes, an important type of reinforcement learning (RL) problem. Maze problems represent a simplified virtual model of real environments that can be used for developing core algorithms of many real-world applications related to the problem of navigation. However, the best achievements of LCSs in maze problems are still mostly bounded to non-aliasing environments, while LCS complexity seems to obstruct a proper analysis of the reasons of failure.

We construct a new LCS agent that has a simpler and more transparent performance mechanism, but that can still solve mazes better than existing algorithms. We use the structure of a predictive LCS model, strip out the evolutionary mechanism, simplify the reinforcement learning procedure and equip the agent with the ability of associative perception, adopted from psychology.

To improve our understanding of the nature and structure of maze environments, we analyze mazes used in research for the last two decades, introduce a set of maze complexity characteristics, and develop a set of new maze environments. We then run our new LCS with associative perception through the old and new aliasing mazes, which represent partially observable Markov decision problems (POMDP) and demonstrate that it performs at least as well as, and in some cases better than, other published systems.
Motivated Learning from Interesting Events: Adaptive, Multitask Learning Agents for Complex Environments
Authors: Merrick Kathryn , Maher Mary Lou
Published: March 2009

This article presents a computational model of motivation for learning agents to achieve adaptive, multitask learning in complex, dynamic environments. Motivation is modeled as an attention focus mechanism to extend existing learning algorithms to environments in which tasks cannot be completely predicted prior to learning. Two agent models are presented for motivated reinforcement learning and motivated supervised learning, which incorporate this model of motivation. The formalisms used to define these agent models further allow the definition of consistent metrics for evaluating motivated learning agent models. The article concludes with a demonstration of the motivated reinforcement learning agent model that uses novelty and interest as the motivation function. The model is evaluated using the new metrics. Results show that motivated reinforcement learning agents using general, task-independent concepts such as novelty and interest can learn multiple, task-oriented behaviors by adapting their focus of attention in response to their changing experiences in their environment.
Enchantment and solidarity
Authors: Cravatte Céline , Chabloz Nadège
Published: March 2009

This article studies the mechanisms of `enchantment' at work in the provision of tourist services, especially in one of its more modern forms: `fair' tourism, linked more broadly to the imaginative world and practices of fair trade. The French associations that promote and put into practice this type of tourism construct a context for meeting the `other' by presenting the consumption of this service as an act of solidarity. This shaping of the relation helps to create states of `enchantment' of tourists, an enchantment that draws power from the participation in a collective project to change the world (related to fair trade) and from the connection with a small producer of the South. However, the creation of this enchantment constitutes a fragile balance between what is hidden and what is revealed, and also depends on the protagonists of the encounter in situ. Here, we study the representations and reactions of tourists through a case study from Burkina Faso. Situations of disenchantment show that the double mechanism of de-fetishization and re-fetishization at the heart of ethical tourism does not always work.
Consuming the city in passing
Authors: Cunin Elisabeth , Rinaudo Christian
Published: March 2009

This article considers the performance of difference in the tourist presentation of Cartagena de Indias, on the Colombian Caribbean coast. The authors centre their analysis on the paseo en chiva, a guided tour in a folkloristic bus, which travels from one tourist site to another, to show how the city becomes an object of consumption through which the local history and culture emerge as easily appropriable global products and signs. Principal site of the slave trade in the territory of New Grenada and contemporary incarnation of a Spanish colonial past, Cartagena is particularly congruous for consideration of the identities of the city and those within it, identities that allude to the marketing of black culture and bodies, and to the evocation of the mestizaje associated with Latin America. At the crossroads between urban and ethnic studies, this article proposes an analysis of the production of a place in which differences are (faceted as) tourist resources which can be consumed itinerantly, thus producing a history and identities which, standardized and stereotyped, in turn act upon the relation of the inhabitants to their city.
Performing Leadership: Towards a New Research Agenda in Leadership Studies?
Authors: Peck Edward , Freeman Tim , Six Perri , Dickinson Helen
Published: March 2009

The notion that leadership involves performance is not new, but there has been little detailed exploration of the implications of theories of performance for contemporary leadership practice. This article differentiates between leadership `is' performance and leadership `as 'performance as one means of investigating contemporary leadership. We suggest that this distinction allows for more sustainable accounts of the relationships between leaders, followers and the institutional settings within which they are generated and, consequently, the spaces in which there is potential for change to occur. The article argues that such insights may be made by combining ideas derived from writers on performance studies and performativity with new-institutionalist theory, the latter emphasising the crucial role of context in shaping the behaviour of leaders, so that their agency is always situated in specific settings.
Review: Rapid virological response to peginterferon alfa and ribavirin treatment of chronic hepatitis C predicts sustained virological response and relapse in genotype 1 patients
Authors: Poordad Fred , Landaverde Carmen
Published: March 2009

The treatment of chronic hepatitis C is a rapidly changing arena with new medications, new guidelines, and an evolving understanding of the virus, host factors and natural history. With the explosion of new information, the educational infrastructure to update clinicians has been outpaced; many feel uncertain if the tools they are using to care for patients are meeting the standard of practice. This review focuses on the most common genotype of the hepatitis C virus and the rules of engagement when treating with pegylated interferon and ribavirin. Viral assessment guideposts are evaluated and put into context for a clinical audience. The expected arrival of newer antiviral therapies is still years away, and maximizing the current treatment regimens is of utmost importance to eradicate virus when feasible, while minimizing toxicity.
Review: Vasoconstrictors for the treatment of portal hypertension
Authors: Hackworth William A. , Sanyal Arun J.
Published: March 2009

Vasoconstrictors have long been used in an attempt to mitigate the effects of portal hypertension. In this review, we discuss the current understanding of portal hypertension and the use of vasoconstrictors in the management of its sequlae, including variceal hemorrhage, hepatorenal syndrome, and paracentesis-induced circulatory dysfunction. Experimental and clinical evidence for the use of vasoconstrictors is considered, and several exciting recent developments are reviewed.