TableButler – a Windows based tool for processing large data tables generated with high-throughput methods

<p>Abstract</p> <p>Background</p> <p>High-throughput "omics" based data analysis play emerging roles in life sciences and molecular diagnostics. This emphasizes the urgent need for user-friendly windows-based software interfaces that could process the diversity of large tab-delimited raw data files generated by these methods. Depending on the study, dozens to hundreds of these data tables are generated. Before the actual statistical or cluster analysis, these data tables have to be combined and merged to expression matrices (e.g., in case of gene expression analysis). Gene annotations as well as information concerning the samples analyzed may be appended, renewed or extended. Often additional data values shall be computed or certain features must be filtered out.</p> <p>Results</p> <p>In order to perform these tasks, we have developed a Microsoft Windows based application, "<b><it>TableButler</it></b>", which allows biologists or clinicians without substantial bioinformatics background to perform a plethora of data processing tasks required to analyze the large-scale data.</p> <p>Conclusion</p> <p><b><it>TableButler </it></b>is a monolithic Windows application. It is implemented to handle, join and preprocess large tab delimited ASCII data files. The intuitive user interface enables scientists (e.g. biologists, clinicians or others) to setup workflows for their specific problems by simple drag-and drop like operations.</p> <p>For more details about <b><it>TableButler</it></b>, visit <url>http://www.OncoExpress.org/software/tablebutler</url>.</p

DNA Copy Number Changes in Human Malignant Fibrous Histiocytomas by Array Comparative Genomic Hybridisation

BACKGROUND: Malignant fibrous histiocytomas (MFHs), or undifferentiated pleomorphic sarcomas, are in general high-grade tumours with extensive chromosomal aberrations. In order to identify recurrent chromosomal regions of gain and loss, as well as novel gene targets of potential importance for MFH development and/or progression, we have analysed DNA copy number changes in 33 MFHs using microarray-based comparative genomic hybridisation (array CGH). PRINCIPAL FINDINGS: In general, the tumours showed numerous gains and losses of large chromosomal regions. The most frequent minimal recurrent regions of gain were 1p33-p32.3, 1p31.3-p31.2 and 1p21.3 (all gained in 58% of the samples), as well as 1q21.2-q21.3 and 20q13.2 (both 55%). The most frequent minimal recurrent regions of loss were 10q25.3-q26.11, 13q13.3-q14.2 and 13q14.3-q21.1 (all lost in 64% of the samples), as well as 2q36.3-q37.2 (61%), 1q41 (55%) and 16q12.1-q12.2 (52%). Statistical analyses revealed that gain of 1p33-p32.3 and 1p21.3 was significantly associated with better patient survival (P = 0.021 and 0.046, respectively). Comparison with similar array CGH data from 44 leiomyosarcomas identified seven chromosomal regions; 1p36.32-p35.2, 1p21.3-p21.1, 1q32.1-q42.13, 2q14.1-q22.2, 4q33-q34.3, 6p25.1-p21.32 and 7p22.3-p13, which were significantly different in copy number between the MFHs and leiomyosarcomas. CONCLUSIONS: A number of recurrent regions of gain and loss have been identified, some of which were associated with better patient survival. Several specific chromosomal regions with significant differences in copy number between MFHs and leiomyosarcomas were identified, and these aberrations may be used as additional tools for the differential diagnosis of MFHs and leiomyosarcomas

Do you get what you pay for? Sales incentives and implications for motivation and changes in turnover intention and work effort

This study investigated relations between pay-for-performance incentives designed to vary in instrumentality (annual pay-for-performance, quarterly pay-for-performance, and base pay level) and employee outcomes (self-reported work effort and turnover intention) in a longitudinal study spanning more than 2 years. After controlling for perceived instrumentality, merit pay increase, and the initial values of the dependent variables, the amount of base pay was positively related to work effort and negatively related to turnover intention, where both relationships were mediated by autonomous motivation. The amounts of quarterly and annual pay-for-performance were both positively related to controlled motivation, but were differently related to the dependent variables due to different relations with autonomous motivation

Exploring the relationships between International Classification of Functioning, Disability and Health (ICF) constructs of Impairment, Activity Limitation and Participation Restriction in people with osteoarthritis prior to joint replacement

<p>Abstract</p> <p>Background</p> <p>The International Classification of Functioning, Disability and Health (ICF) proposes three main constructs, impairment (I), activity limitation (A) and participation restriction (P). The ICF model allows for all paths between the constructs to be explored, with significant paths likely to vary for different conditions. The relationships between I, A and P have been explored in some conditions but not previously in people with osteoarthritis prior to joint replacement. The aim of this paper is to examine these relationships using separate measures of each construct and structural equation modelling.</p> <p>Methods</p> <p>A geographical cohort of 413 patients with osteoarthritis about to undergo hip and knee joint replacement completed the Aberdeen measures of Impairment, Activity Limitation and Participation Restriction (Ab-IAP). Confirmatory factor analysis was used to test the three factor (I, A, P) measurement model. Structural equation modelling was used to explore the I, A and P pathways in the ICF model.</p> <p>Results</p> <p>There was support from confirmatory factor analysis for the three factor I, A, P measurement model. The structural equation model had good fit [S-B Chi-square = 439.45, df = 149, CFI robust = 0.91, RMSEA robust = 0.07] and indicated significant pathways between I and A (standardised coefficient = 0.76 p < 0.0001) and between A and P (standardised coefficient = 0.75 p < 0.0001). However, the path between I and P was not significant (standardised coefficient = 0.01).</p> <p>Conclusion</p> <p>The significant pathways suggest that treatments and interventions aimed at reducing impairment, such as joint replacement, may only affect P indirectly, through A, however, longitudinal data would be needed to establish this.</p

Health-related quality of life change in patients treated at a multidisciplinary pain clinic

Background Multidisciplinary pain management (MPM) is a generally accepted method for treating chronic pain, but heterogeneous outcome measures provide only limited conclusions concerning its effectiveness. Therefore, further studies on the effectiveness of MPM are needed to identify subgroups of patients who benefit, or do not benefit, from these interventions. Our aim was to analyse health-related quality of life (HRQoL) changes after MPM and to identify factors associated with treatment outcomes. Methods We carried out a real world observational follow-up study of chronic pain patients referred to a tertiary multidisciplinary outpatient pain clinic to describe, using the validated HRQoL instrument 15D, the HRQoL change after MPM and to identify factors associated with this change. 1,043 patients responded to the 15D HRQoL questionnaire at baseline and 12 months after the start of treatment. Background data were collected from the pre-admission questionnaire of the pain clinic. Results Fifty-three percent of the patients reported a clinically important improvement and, of these, 81% had a major improvement. Thirty-five percent reported a clinically important deterioration, and 12% had no change in HRQoL. Binary logistic regression analysis revealed that major improvement was positively associated with shorter duration of pain (Peer reviewe

Maintaining a balance: a focus group study on living and coping with chronic whiplash-associated disorder

<p>Abstract</p> <p>Background</p> <p>There is little qualitative insight into how persons with chronic Whiplash-Associated Disorder cope on a day to day basis. This study seeks to identify the symptoms persons with Whiplash-Associated Disorder describe as dominating and explore their self-initiated coping strategies.</p> <p>Methods</p> <p>Qualitative study using focus groups interviews. Fourteen Norwegian men and women with Whiplash-Associated Disorder (I or II) were recruited to participate in two focus groups. Data were analyzed according to a phenomenological approach, and discussed within the model of Cognitive Activation Theory of Stress (CATS).</p> <p>Results</p> <p>Participants reported neck and head pain, sensory hypersensitivity, and cognitive dysfunction following their whiplash injury. Based on the intensity of symptoms, participants divided everyday life into good and bad periods. In good periods the symptoms were perceived as manageable. In bad periods the symptoms intensified and took control of the individual. Participants expressed a constant notion of trying to balance their three main coping strategies; rest, exercise, and social withdrawal. In good periods participants experienced coping by expecting good results from the strategies they used. In bad periods they experienced no or negative relationships between their behavioral strategies and their complaints.</p> <p>Conclusions</p> <p>Neck and head pain, sensory hypersensitivity, and cognitive dysfunction were reported as participants' main complaints. A constant notion of balancing between their three main coping strategies; rest, exercise, and social withdrawal, was described.</p

Careers in context: An international study of career goals as mesostructure between societies' career-related human potential and proactive career behaviour

Careers exist in a societal context that offers both constraints and opportunities for career actors. Whereas most studies focus on proximal individual and/or organisational-level variables, we provide insights into how career goals and behaviours are understood and embedded in the more distal societal context. More specifically, we operationalise societal context using the career-related human potential composite and aim to understand if and why career goals and behaviours vary between countries. Drawing on a model of career structuration and using multilevel mediation modelling, we draw on a survey of 17,986 employees from 27 countries, covering nine of GLOBE's 10 cultural clusters, and national statistical data to examine the relationship between societal context (macrostructure building the career-opportunity structure) and actors' career goals (career mesostructure) and career behaviour (actions). We show that societal context in terms of societies' career-related human potential composite is negatively associated with the importance given to financial achievements as a specific career mesostructure in a society that is positively related to individuals' proactive career behaviour. Our career mesostructure fully mediates the relationship between societal context and individuals' proactive career behaviour. In this way, we expand career theory's scope beyond occupation- and organisation-related factors

Genome-Wide Profiling of Histone H3 Lysine 4 and Lysine 27 Trimethylation Reveals an Epigenetic Signature in Prostate Carcinogenesis

BACKGROUND: Increasing evidence implicates the critical roles of epigenetic regulation in cancer. Very recent reports indicate that global gene silencing in cancer is associated with specific epigenetic modifications. However, the relationship between epigenetic switches and more dynamic patterns of gene activation and repression has remained largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide profiling of the trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) was performed using chromatin immunoprecipitation coupled with whole genome promoter microarray (ChIP-chip) techniques. Comparison of the ChIP-chip data and microarray gene expression data revealed that loss and/or gain of H3K4me3 and/or H3K27me3 were strongly associated with differential gene expression, including microRNA expression, between prostate cancer and primary cells. The most common switches were gain or loss of H3K27me3 coupled with low effect on gene expression. The least prevalent switches were between H3K4me3 and H3K27me3 coupled with much higher fractions of activated and silenced genes. Promoter patterns of H3K4me3 and H3K27me3 corresponded strongly with coordinated expression changes of regulatory gene modules, such as HOX and microRNA genes, and structural gene modules, such as desmosome and gap junction genes. A number of epigenetically switched oncogenes and tumor suppressor genes were found overexpressed and underexpressed accordingly in prostate cancer cells. CONCLUSIONS/SIGNIFICANCE: This work offers a dynamic picture of epigenetic switches in carcinogenesis and contributes to an overall understanding of coordinated regulation of gene expression in cancer. Our data indicate an H3K4me3/H3K27me3 epigenetic signature of prostate carcinogenesis

Hyperoxic Treatment Induces Mesenchymal-to-Epithelial Transition in a Rat Adenocarcinoma Model

Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (∼16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the “switches” of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects

Low BMI-1 expression is associated with an activated BMI-1-driven signature, vascular invasion, and hormone receptor loss in endometrial carcinoma

We studied the expression of polycomb group (PcG) protein BMI-1 in a large population-based patient series of endometrial carcinomas in relation to clinical and molecular phenotype. Also, 57 fresh frozen endometrial carcinomas were studied for the relationship between BMI-1 protein expression, BMI-1 mRNA level, and activation of an 11-gene signature reported to represent a BMI-1-driven pathway. BMI-1 protein expression was significantly weaker in tumours with vascular invasion (P<0.0001), deep myometrial infiltration (P=0.004), and loss of oestrogen receptor (ER) (P<0.0001) and progesterone receptors (PR) (P=0.03). Low BMI-1 protein expression was highly associated with low BMI-1 mRNA expression (P=0.002), and similarly low BMI-1 mRNA expression correlated significantly with vascular invasion, ER and PR loss, and histologic grade 3. In contrast, activation of the reported 11-gene signature, supposed to represent a BMI-1-driven pathway, correlated with low mRNA expression of BMI-1 (P<0.001), hormone receptor loss, presence of vascular invasion, and poor prognosis. We conclude that BMI-1 protein and mRNA expression are significantly correlated and that BMI-1 expression is inversely associated with activation of the 11-gene signature. Loss of BMI-1 seems to be associated with an aggressive phenotype in endometrial carcinomas