Measuring the implementation of codes of conduct. An assessment method based on a process approach of the responsible organisation

More and more organisations formulate a code of conduct in order to stimulate responsible behaviour among their members. Much time and energy is usually spent fixing the content of the code but many organisations get stuck in the challenge of implementing and maintaining the code. The code then turns into nothing else than the notorious “paper in the drawer”, without achieving its aims. The challenge of implementation is to utilize the dynamics which have emerged from the formulation of the code. This will support a continuous process of reflection on the central values and standards contained in the code. This paper presents an assessment method, based on the EFQM model, which intends to support this implementation process

Reprint of "Anti-therapeutic antibodies and their clinical impact in patients treated with the TNF antagonist adalimumab".

Highlights • ECL-based assays for measurement of adalimumab and adalimumab antibodies. • Performance of ECL antibody assay not significantly improved by acid dissociation. • Negative correlation between levels of antibody and free adalimumab. • Negative correlation between adalimumab level and disease activity scores

Dietary enrichment of apolipoprotein E-deficient mice with extra virgin olive oil in combination with seal oil inhibits atherogenesis

<p>Abstract</p> <p>Background</p> <p>In this study we investigated the antiatherogenic effect of dietary enrichment of a combination of extra virgin olive oil (EVO) and seal oil on apolipoprotein E-deficient (apoE^-/-).</p> <p>Methods</p> <p>Six-week-old female and male apoE^-/-mice were for 12 weeks fed a lipid rich diet containing 19.5% fat and 1.25% cholesterol without any supplement, with 1% (wt/wt) mixture of extra virgin olive and seal oil (EVO/n-3), or 1% corn oil, respectively.</p> <p>Results</p> <p>Supplementation with the combination of EVO/n-3 significantly reduced atherosclerotic lesion formation in the aortic arch, thoracoabdominal, and total aorta of female apoE^-/-mice. The effect was less pronounced in male mice and significant reduction was only observed in the thoracoabdominal region of the aorta. There were no differences or changes in dietary intake or body weight gain. However, compared to the other groups, plasma levels of triglycerides were reduced in both female and male mice fed the EVO/n-3 mixture. Male mice on both treatments showed reduced plasma cholesterol compared to the control mice after 12 weeks on diet.</p> <p>Conclusion</p> <p>Dietary supplementation of a marine/olive oil combination inhibits atherosclerotic lesion formation in the female apoE^-/-mice by antithrombotic, antihypertriglyceridemic, and antioxidant effects.</p

Dietary enrichment of apolipoprotein E-deficient mice with extra virgin olive oil in combination with seal oil inhibits atherogenesis

Background: In this study we investigated the antiatherogenic effect of dietary enrichment of a combination of extra virgin olive oil (EVO) and seal oil on apolipoprotein E-deficient (apoE(-/-)). Methods: Six-week-old female and male apoE(-/-) mice were for 12 weeks fed a lipid rich diet containing 19.5% fat and 1.25% cholesterol without any supplement, with 1% (wt/wt) mixture of extra virgin olive and seal oil (EVO/n-3), or 1% corn oil, respectively. Results: Supplementation with the combination of EVO/n-3 significantly reduced atherosclerotic lesion formation in the aortic arch, thoracoabdominal, and total aorta of female apoE(-/-) mice. The effect was less pronounced in male mice and significant reduction was only observed in the thoracoabdominal region of the aorta. There were no differences or changes in dietary intake or body weight gain. However, compared to the other groups, plasma levels of triglycerides were reduced in both female and male mice fed the EVO/n-3 mixture. Male mice on both treatments showed reduced plasma cholesterol compared to the control mice after 12 weeks on diet. Conclusion: Dietary supplementation of a marine/olive oil combination inhibits atherosclerotic lesion formation in the female apoE(-/-) mice by antithrombotic, antihypertriglyceridemic, and antioxidant effects

Biopolymer-based structuring of liquid oil into soft solids and oleogels using water-continuous emulsions as templates

Physical trapping of a hydrophobic liquid oil in a matrix of water-soluble biopolymers was achieved using a facile two-step process by first formulating a surfactant-free oil-in-water emulsion stabilized by biopolymers (a protein and a polysaccharide) followed by complete removal of the water phase (by either high- or low-temperature drying of the emulsion) resulting in structured solid systems containing a high concentration of liquid oil (above 97 wt %). The microstructure of these systems was revealed by confocal and cryo-scanning electron microscopy, and the effect of biopolymer concentrations on the consistency of emulsions as well as the dried product was evaluated using a combination of small-amplitude oscillatory shear rheometry and large deformation fracture studies. The oleogel prepared by shearing the dried product showed a high gel strength as well as a certain degree of thixotropic recovery even at high temperatures. Moreover, the reversibility of the process was demonstrated by shearing the dried product in the presence of water to obtain reconstituted emulsions with rheological properties comparable to those of the fresh emulsion

Identifying Resistance Mechanisms against Five Tyrosine Kinase Inhibitors Targeting the ERBB/RAS Pathway in 45 Cancer Cell Lines

Because of the low overall response rates of 10-47% to targeted cancer therapeutics, there is an increasing need for predictive biomarkers. We aimed to identify genes predicting response to five already approved tyrosine kinase inhibitors. We tested 45 cancer cell lines for sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib at the clinically administered doses. A resistance matrix was determined, and gene expression profiles of the subsets of resistant vs. sensitive cell lines were compared. Triplicate gene expression signatures were obtained from the caArray project. Significance analysis of microarrays and rank products were applied for feature selection. Ninety-five genes were also measured by RT-PCR. In case of four sunitinib resistance associated genes, the results were validated in clinical samples by immunohistochemistry. A list of 63 top genes associated with resistance against the five tyrosine kinase inhibitors was identified. Quantitative RT-PCR analysis confirmed 45 of 63 genes identified by microarray analysis. Only two genes (ANXA3 and RAB25) were related to sensitivity against more than three inhibitors. The immunohistochemical analysis of sunitinib-treated metastatic renal cell carcinomas confirmed the correlation between RAB17, LGALS8, and EPCAM and overall survival. In summary, we determined predictive biomarkers for five tyrosine kinase inhibitors, and validated sunitinib resistance biomarkers by immunohistochemistry in an independent patient cohort. © 2013 Pénzváltó et al

Differential Gene Expression Patterns of EBV Infected EBNA-3A Positive and Negative Human B Lymphocytes

The genome of Epstein-Barr virus (EBV) encodes 86 proteins, but only a limited set is expressed in EBV–growth transformed B cells, termed lymphoblastoid cell lines (LCLs). These cells proliferate via the concerted action of EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), some of which are rate limiting to establish a stable homeostasis of growth promoting and anti-apoptotic activities. We show here that EBV mutants, which lack the EBNA-3A gene, are impaired but can still initiate cell cycle entry and proliferation of primary human B cells in contrast to an EBNA-2 deficient mutant virus. Surprisingly, and in contrast to previous reports, these viral mutants are attenuated in growth transformation assays but give rise to permanently growing EBNA-3A negative B cell lines which exhibit reduced proliferation rates and elevated levels of apoptosis. Expression profiles of EBNA-3A deficient LCLs are characterized by 129 down-regulated and 167 up-regulated genes, which are significantly enriched for genes involved in apoptotic processes or cell cycle progression like the tumor suppressor gene p16/INK4A, or might contribute to essential steps of the viral life cycle in the infected host. In addition, EBNA-3A cellular target genes remarkably overlap with previously identified targets of EBNA-2. This study comprises the first genome wide expression profiles of EBNA-3A target genes generated within the complex network of viral proteins of the growth transformed B cell and permits a more detailed understanding of EBNA-3A's function and contribution to viral pathogenesis

Variation of PEAR1 DNA methylation influences platelet and leukocyte function.

Background Platelet-endothelial aggregation receptor 1 (PEAR-1) is a transmembrane receptor involved in platelet activation and megakaryopoiesis whose expression is driven by DNA methylation. PEAR1 variants were associated with differential platelet response to activation and cardiovascular outcomes. We aimed at investigating the link between PEAR1 methylation and platelet and leukocyte function markers in a family-based population. Results We measured PEAR1 methylation in 605 Moli-family participants with available blood counts, plasma P-selectin and C-reactive protein, whole blood platelet P-selectin, and platelet-leukocyte mixed conjugate measurements. We performed principal component analysis (PCA) to identify groups of highly correlated CpG sites. We used linear mixed regression models (using age, gender, BMI, smoking, alcohol drinking, being a proband for family recruitment, being a member of myocardial infarction (MI) family as fixed effects, and family as a random effect) to evaluate associations between PEAR1 methylation and phenotypes. PEAR1 methylation Factor2, characterized by the previously identified megakaryocyte-specific CpG sites, was inversely associated with platelet-monocyte conjugates, P-selectin, and WBC counts, while positively associated with the platelet distribution width (PDW) and with leukocyte CD11b and L-selectin. Moreover, PEAR1 Factor2 methylation was negatively associated with INFLAscore, a low-grade inflammation score. The latter was partially mediated by the PEAR1 methylation effect on platelet variables. PEAR1 methylation association with WBC measurements and INFLAscore was confirmed in the independent cohort FLEMENGHO. Conclusions We report a significant link between epigenetic signatures in a platelet functional gene and inflammation-dependent platelet function variability measured in two independent cohorts