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Background and aims: Second‐generation direct‐acting antivirals (2G DAA) to cure HCV have led to dramatic clinical improvements. HCV‐associated hepatocellular carcinoma (HCC), however, remains common. Impaired immune tumor surveillance may play a role in HCC development. Our cohort evaluated the effects of innate immune types and clinical variables on outcomes including HCC. Methods: Participants underwent full HLA class I/KIR typing and long‐term HCV follow‐up. Results: A total of 353 HCV+ participants were followed for a mean of 7 years. Cirrhosis: 25% at baseline, developed in 12% during follow‐up. 158 participants received 2G DAA therapy. HCC developed without HCV therapy in 20 subjects, 24 HCC after HCV therapy, and 10 of these after 2G DAA. Two predictors of HCC among 2G DAA‐treated patients: cirrhosis (OR, 10.0, p = 0.002) and HLA/KIR profiles predicting weak natural killer (NK) cell‐mediated immunity (NK cell complementation groups 6, 9, 11, 12, OR of 5.1, p = 0.02). Without 2G DAA therapy: cirrhosis was the main clinical predictor of HCC (OR, 30.8, p < 0.0001), and weak NK‐cell‐mediated immunity did not predict HCC. Conclusion: Cirrhosis is the main risk state predisposing to HCC, but weak NK‐cell‐mediated immunity may predispose to post‐2G DAA HCC more than intermediate or strong NK‐cell‐mediated immunity. [ABSTRACT FROM AUTHOR]

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1559-1816.2010.00629.x Byline: James C. Ryan (1,2) Abstract: This study examined the factor structure and scale reliability of the Motivation Sources Inventory (MSI; Barbuto & Scholl, 1998), an instrument designed to measure the motivational concepts contained within the meta-theory of motivation (Leonard, Beauvais, & Scholl, 1999). Participants were comprised of financial-service professionals, health-industry administrators, and retail and distribution workers, all engaged in full-time employment in Ireland. Data were collected through the administration of the Motivation Source Inventory (MSI) to a sample of working professionals (N = 252). Factor analyses, scale reliabilities, and inter-item correlations were conducted. Results of the current study did not support the scale structure reported by the instrument developers. The implications of these results and suggestions for future research are presented. Author Affiliation: (*)Department of Management, Marketing, and Public AdministrationUniversity of SharjahSharjah, United Arab Emirates Article note: (2) James C. Ryan, Department of Management, Marketing, and Public Administration, College of Business Administration, University of Sharjah, P. O. Box 27272, Sharjah, United Arab Emirates. E-mail: jcryanphd@gmail.com

Purpose: The purpose of this paper is to shed light on the use of bibliometric indicators as a people analytics tool for examining research performance outcome differences in faculty mobility and turnover. Design/methodology/approach: Employing bibliometric information from research databases, the publication, citations, h-index and newly developed individual annualized h-index (hIa-index) for a sample of university faculty is examined (N = 684). Information relating to turnover decisions from a human resource (HR) information system and bibliometric data from a research database are combined to explore research performance differences across cohorts of retained, resigned or terminated faculty over a five-year period in a single university. Findings: Analysis of variance (ANOVA) results indicate traditional bibliometric indicators of h-index, publication count and citation count which are limited in their ability to identify performance differences between employment status cohorts. Results do show some promise for the newly developed hIa-index, as it is found to be significantly lower for terminated faculty (p < 0.001), as compared to both retained and resigned faculty. Multinomial logistic regression analysis also confirms the hIa metric as a predictor of terminated employment status. Research limitations/implications: First, the results imply that the hIa-index, which controls for career length and elements of coauthorship is a superior bibliometric indicator for comparison of research performance. Practical implications: Results suggest that the hIa metric may serve as a useful tool for the examination of employment decisions for universities. It also highlights the potential usefulness of bibliometric indicators for people analytics and the examination of employment decisions, performance management and faculty turnover in research-intensive higher education contexts. Originality/value: This empirical paper is entirely unique. No research has previously examined the issue of turnover in a university setting using the bibliometric measures employed here. This is a first example of the potential use of hIa bibliometric index as an HR analytics tool for the examination of HR decisions such as employee turnover in the university context. [ABSTRACT FROM AUTHOR]

Abstract Background Ciguatoxins (CTXs) are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO) and molecular pathway enrichment of the gene expression data. Results A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p < 0.0001) with microarray results. Conclusions Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against neuroinflammation. Pathologic activity of the complement/coagulation cascade has been shown in patients suffering from a chronic form of ciguatera poisoning and is of particular interest in this model. Anti-inflammatory processes were at work not only in the brain but were also seen in whole blood and liver of these animals, creating a systemic anti-inflammatory environment to protect against the initial cellular damage caused by the toxin.

The United Arab Emirates (UAE) is a young, oil-rich country, where national youth display a clear preference for public sector employment. Growing youth unemployment reinforces the importance of non-government employment, including entrepreneurship. This study investigates UAE national youth intentions toward entrepreneurship through the Theory of Planned Behavior and the Entrepreneurial Intention Questionnaire (EIQ). Analysis (N = 544) identifies the direct influence of attitude and perceived behavioral control and indirect influence of subjective norms on entrepreneurship intention. Results also examine several demographic variables and highlight the potential importance of family and social groups in promoting entrepreneurial intentions in this emerging country context. [ABSTRACT FROM AUTHOR]

In our previous study, we observed a severe reduction in the Src homology 2-containing-inositol-phosphatase-1 (SHIP1) protein in a subpopulation of subjects from a small adult Crohn's Disease (CD) cohort. This pilot study had been undertaken since we had previously demonstrated that engineered deficiency of SHIP1 in mice results in a spontaneous and severe CD-like ileitis. Here, we extend our analysis of SHIP1 expression in peripheral blood mononuclear cells in a second much larger adult Inflammatory Bowel Disease (IBD) cohort, comprised of both CD and Ulcerative Colitis patients, to assess contribution of SHIP1 to the pathogenesis of human IBD. SHIP1 protein and mRNA levels were evaluated from blood samples obtained from IBD subjects seen at UCSF/SFVA, and compared to healthy control samples. Western blot analyses revealed that ~15% of the IBD subjects are severely SHIP1-deficient, with less than 10% of normal SHIP1 protein present in PBMC. Further analyses by flow cytometry and sequencing were performed on secondary samples obtained from the same subjects. Pan-hematolymphoid SHIP1 deficiency was a stable phenotype and was not due to coding changes in the INPP5D gene. A very strong association between SHIP1 deficiency and the presence of a novel SHIP1:ATG16L1 fusion transcript was seen. Similar to SHIP1-deficient mice, SHIP1-deficient subjects had reduced numbers of circulating CD4+ T cell numbers. Finally, SHIP1-deficient subjects with CD had a history of severe disease requiring multiple surgeries. These studies reveal that the SHIP1 protein is crucial for normal T cell homeostasis in both humans and mice, and that it is also a potential therapeutic and/or diagnostic target in human IBD. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to extend the current debate on value-intention link by investigating the hitherto unexplored relation between the concepts of the multidimensional work ethic profile and entrepreneurial intentions (EIs). In addition, this research seeks to offer specific insight into the work values and EIs of United Arab Emirates (UAE) national youth in an effort to contribute to decision making and policy formation for enhancing entrepreneurship. Design/methodology/approach – In total, 309 UAE youth completed an Arabic version of the short form multidimensional work ethic profile (MWEP-SF) and a measure of EI. Findings – Results confirm the value-intention link and support the view that values can direct work choices in entrepreneurship. The regression model identifies that the work ethics of wasted time, leisure, and self-reliance positively predict EI, while centrality of work is unrelated to EI. Originality/value – The relation between work values and EI of youth is underexplored in the context of the UAE. The current extreme underrepresentation of UAE nationals in the private sector of the UAE economy highlights a significant problem for the UAE strategy of workforce nationalization. As the current findings reveal that the UAE youth possess work values which can predict EIs, the policy initiatives in the UAE may encourage Emirati nationals to more actively participate in the new venture creation and development. This will potentially facilitate the government to achieve the balance between public sector employability and self-employment contributions in the private sector. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to provide an empirical examination of the factors affecting voluntary eService adoption in a public sector work environment. The model examined was constructed following a thorough review of relevant literature on technology adoption through the framework of Theory of Interpersonal Behaviour. Structural equation modelling was used to examine a model assessed through participant responses to survey data for a sample of 515 respondents working in Australian City Councils. The results indicate that an individual's attitudes and beliefs have a significant influence on eService utilisation. Results also suggest that organisational conditions such as training, leadership support and organisational preparedness act to enhance eService utilisation indirectly through their effect on an individual's attitudes and beliefs. The current study provides a model of examining and explaining voluntary technology adoption behaviour in the workplace. [ABSTRACT FROM AUTHOR]

Background: Ciguatoxins (CTXs) are polyether marine neurotoxins found in multiple reef-fish species and are potent activators of voltage-gated sodium channels. It is estimated that up to 500,000 people annually experience acute ciguatera poisoning from consuming toxic fish and a small percentage of these victims will develop a chronic, multisymptom, multisystem illness, which can last years, termed a Chronic Inflammatory Response Syndrome (CIRS). Symptoms of ciguatera CIRS include fatigue, cognitive deficits, neurologic deficits, pain and sensitivity to light. There are few treatment options for ciguatera CIRS since little is known about its pathophysiology. Methods: This study characterizes the transcriptional profile in whole blood of 11 patients with ciguatera-induced CIRS and 11 normal controls run in duplicate using Agilent one color whole genome microarrays. Differential expression was determined by using a combination of moderated t-test p-value and fold change (FC). Significant genes were subjected to gene ontology, principal component analysis and SVM classification. Seven significant genes found by microarray were validated by PCR. Results: Using a low stringency (p < 0.05 and FC > 1.4) and a high stringency (p < 0.01 and FC > 1.5) filter, the resulting gene sets of 185 and 55, respectively, showed clear separation of cases and controls by PCA as well as 100% classification accuracy by SVM, indicating that the gene profiles can separate patients from controls. PCR results of 7 genes showed a 95% correlation to microarray data. Several genes identified by microarray are important in wound healing (CD9, CD36, vWF and Factor XIII), adaptive immunity (HLA-DQB1, DQB2, IL18R1 and IL5RA) and innate immunity (GZMK, TOLLIP, SIGIRR and VIPR2), overlapping several areas shown to be disrupted in a mouse model of acute exposure to ciguatoxin. Another area of interest was differential expression of long, non-coding sequences, or lncRNA. Conclusions: Disruptions of innate and adaptive immune mechanisms were recorded at both the genomic and proteomic level. A disruption in the HLA-T cell receptor axis could indicate HLA haplotype sensitivity for this chronic syndrome, as noted in many autoimmune conditions. Taken together, these indicators of illness provide additional insights into pathophysiology and potential therapies. [ABSTRACT FROM AUTHOR]

This research examines the work motivation profile of research scientists and the effect of work motivation on research performance. A sample of United Kingdom-based research scientists ( N = 405) working in the chemical, biological and biomedical research domains took part in the study. Participants completed a survey based measure of motivational sources and self-report research performance evaluation. The motivational sources of internal self-concept motivation and instrumental motivation were found to be the strongest and weakest respectively for research scientists. External self-concept motivation was found to be significantly higher among younger scientists. No gender differences were found in the motivational profile of scientists. While controlling for the influences of age and gender, internal self-concept motivation was found to have a significant positive effect on research performance, and instrumental motivation was found to have a significant negative effect on research performance. Consistent with prior research, differences in research performance across age and gender were also identified. The implications of these findings for our understanding of the effective management of scientific research are discussed. [ABSTRACT FROM AUTHOR]

Estuarine crustaceans are often exposed to low dissolved O2 (hypoxia) accompanied by elevated CO2 (hypercapnia), which lowers water pH. Acclimatory responses to hypoxia have been widely characterized; responses to hypercapnia in combination with hypoxia (hypercapnic hypoxia) are less well known. Here we used oligonucleotide microarrays to characterize changes in global gene expression in the hepatopancreas of Pacific whiteleg shrimp, Litopenaeus vannamei, exposed to hypoxia or hypercapnic hypoxia for 4 or 24 h, compared with time-matched animals held in air-saturated water (normoxia). Unigenes whose expressions were significantly impacted by treatment and/or time were used to build artificial neural networks (ANNs) to identify genes with the greatest sensitivity in pairwise discriminations between treatments at each time point and between times for each treatment. ANN gene sets that discriminated hypoxia or hypercapnic hypoxia from normoxia shared functions of translation, mitochondrial energetics, and cellular defense. GO terms protein modification/ phosphorylation/cellular protein metabolism and RNA processing/ apoptosis/cell cycling occurred at highest frequency in discriminating hypercapnic hypoxia from hypoxia at 4 and 24 h, respectively. For 75.4% of the annotated ANN genes, exposure to hypercapnic hypoxia for 24 h reduced or reversed the transcriptional response to hypoxia alone. These results suggest that high CO2/low pH may interfere with transcriptionally based acclimation to hypoxia or elicit physiological or biochemical responses that relieve internal hypoxia. Whether these data reflect resilience or sensitivity of L. vannamei in the face of expanding hypoxic zones and rising levels of atmospheric CO2 may be important to understanding the survival of this and other estuarine species. [ABSTRACT FROM AUTHOR]

Background: The long-term consequences of unsuccessful interferon-α based hepatitis C treatment on liver disease progression and survival have not been fully explored. Methods and Findings: We performed retrospective analyses to assess long-term clinical outcomes among treated and untreated patients with hepatitis C virus in two independent cohorts from a United States Veterans Affairs Medical Center and a University Teaching Hospital. Eligible patients underwent liver biopsy during consideration for interferon-α based treatment between 1992 and 2007. They were assessed for the probability of developing cirrhosis and of dying during follow-up using Cox proportional hazards models, stratified by pretreatment liver fibrosis stage and adjusted for known risk factors for cirrhosis and characteristics affecting treatment selection. The major predictor was a time-dependent covariate for treatment outcome among four patient groups: 1) patients with sustained virological response to treatment; 2) treatment relapsers; 3) treatment nonresponders; and 4) never treated patients. Treatment nonresponders in both cohorts had a statistically significantly increased hazard of cirrhosis compared to never treated patients, as stratified by pretreatment liver fibrosis stage and adjusted for clinical and psychosocial risk factors that disproportionately affect patients who were ineligible for treatment (Veterans Affairs HR = 2.35, CI 1.18–4.69, mean follow-up 10 years, and University Hospital HR = 5.90, CI 1.50–23.24, mean follow-up 7.7 years). Despite their increased risk for liver disease progression, the overall survival of nonresponders in both cohorts was not significantly different from that of never treated patients. Conclusion: These unexpected findings suggest that patients who receive interferon-α based therapies but fail to clear the hepatitis C virus may have an increased hazard of cirrhosis compared to untreated patients. [ABSTRACT FROM AUTHOR]

Abstract: The marine neurotoxin domoic acid (DA) is a rigid analogue of the neurotransmitter glutamate and a potent agonist of kainate subtype glutamate receptors. Persistent activation of these receptor subtypes results in rapid excitotoxicity, calcium-dependent cell death, and neuronal degeneration in regions of the brain where glutamatergic pathways are concentrated. Previous work has shown that DA promotes the expression of inflammatory genes in the brain, such as cyclooxygenase 2 (COX2). To investigate the impact of inflammation on the development of neurodegeneration, and ultimately survival following DA administration, we used selective (L745337, Merck) and non-selective (acetylsalicylic acid (ASA)) COX inhibitors in DA exposed mice. Adult male ICR mice were given a regime of either ASA or L23547 both before and after a single LD50 dose of DA. Mice were observed immediately after toxin introduction and then sacrificed at 2 days post exposure. Our lower dose of L23547 increased survival and was most effective at decreasing neuronal degeneration in the CA1 and CA3 regions of the hippocampus, areas especially sensitive to DA excitotoxicity. This study shows that COX2 plays a role in DA induced neurodegeneration and death, and that inhibitors may be of value for treatment in human and wildlife DA exposure. [ABSTRACT FROM AUTHOR]

We have investigated whether rat Ly49 receptors can monitor Listeria-infected intestinal epithelial cells through altered expression of MHC class I molecules. The rat colon carcinoma epithelial cell line CC531 infected with Listeria expressed higher levels of both classical and nonclassical MHC-I molecules. Reporter cells expressing the activating Ly49s5 receptor displayed increased stimulatory responses when incubated with Listeria-infected CC531 cells in vitro, which could be blocked with mAb 8G10 specific for nonclassical MHC-I molecules of the RT1 haplotype, but not with mAb OX18 reacting with classical MHC-I molecules in this haplotype. Similar responses were observed against IFN-γ-treated cells that also upregulated their expression of MHC-I molecules. Thus, the Ly49s5 receptor can respond to increased levels of nonclassical MHC-I molecules induced on target cells by either bacterial infection or cytokine stimulation. We furthermore found that splenic NK and NKT cells produced IFN-γ in response to Listeria-infected CC531 cells, and that this was not limited to Ly49-expressing cells, since similar levels of IFN-γ production were observed in Ly49 and Ly49 NK cell subsets. Therefore, NK cells may recognize Listeria-infected cells through both MHC-I-dependent and -independent innate immune receptor systems. [ABSTRACT FROM AUTHOR]