Adherence in paediatric renal failure and dialysis: an ethical analysis of nurses' attitudes and reported practice.

Minors have difficulty adhering to the strict management regimen required whilst on renal dialysis for chronic renal failure. This leads to ethical tensions as healthcare professionals (HCPs) and parents try, in the minor's best interests, to ensure s/he adheres. All 11 dialysis nurses working in a large, regional paediatric dialysis unit were interviewed about their perceptions and management of non-adherence and the ethical issues this raised for them. Participants reported negative attitudes to non-adherence alongside sympathy and feelings of frustration. They discussed the competing responsibilities between nurses, parents and minors, and how responsibility ought to be transferred to the minor as s/he matures; the need for minors to take responsibility ahead of transferring to adult services; and, the process of transferring this responsibility. Our discussion concentrates on the ethical issues raised by the participants' reports of how they respond to non-adherence using persuasion and coercion. We consider how understandings of capacity, traditional individual autonomy, and willpower can be used to comprehend the issue of non-adherence. We consider the relational context in which the minor receives, and participates in, healthcare. This exposes the interdependent triad of relationships between HCP, parent and minor and aids understanding of how to provide care in an ethical way. Relational ethics is a useful alternative understanding for professionals reflecting upon how they define their obligations in this context.

Transmission FT-IR chemical imaging on glass substrates: applications in infrared spectral histopathology.

Fourier transform-infrared (FT-IR) chemical imaging in transmission mode has traditionally been performed on expensive mid-IR transparent windows such as barium/calcium fluoride, which are more fragile than glass, making preparation in the histopathology laboratories more cumbersome. A solution is presented here by using cheap glass substrates for the FT-IR chemical imaging, which has a high-wavenumber transmission window allowing measurement of the C-H, N-H, and O-H stretches occurring at ca. 2500-3800 cm(-1). The "fingerprint" region of the IR spectrum occurring below 1800 cm(-1) is not obtainable; however, we demonstrate that a wealth of information is contained in the high wavenumber range using 71 patients on a breast tissue microarray (TMA) as a model for investigation. Importantly, we demonstrate that the tissue can be classified into four basic tissue cell types and that using just the epithelial cells, reasonable discrimination of normal and malignant tissue can be found.

Role of Systemic Factors in Improving the Prognosis of Diabetic Retinal Disease and Predicting Response to Diabetic Retinopathy Treatment.

Topic: To review clinical evidence on systemic factors that might be relevant to update diabetic retinal disease (DRD) staging systems, including prediction of DRD onset, progression, and response to treatment. Clinical relevance: Systemic factors may improve new staging systems for DRD to better assess risk of disease worsening and predict response to therapy. Methods: The Systemic Health Working Group of the Mary Tyler Moore Vision Initiative reviewed systemic factors individually and in multivariate models for prediction of DRD onset or progression (i.e., prognosis) or response to treatments (prediction). Results: There was consistent evidence for associations of longer diabetes duration, higher glycosylated hemoglobin (HbA1c), and male sex with DRD onset and progression. There is strong trial evidence for the effect of reducing HbA1c and reducing DRD progression. There is strong evidence that higher blood pressure (BP) is a risk factor for DRD incidence and for progression. Pregnancy has been consistently reported to be associated with worsening of DRD but recent studies reflecting modern care standards are lacking. In studies examining multivariate prognostic models of DRD onset, HbA1c and diabetes duration were consistently retained as significant predictors of DRD onset. There was evidence of associations of BP and sex with DRD onset. In multivariate prognostic models examining DRD progression, retinal measures were consistently found to be a significant predictor of DRD with little evidence of any useful marginal increment in prognostic information with the inclusion of systemic risk factor data apart from retinal image data in multivariate models. For predicting the impact of treatment, although there are small studies that quantify prognostic information based on imaging data alone or systemic factors alone, there are currently no large studies that quantify marginal prognostic information within a multivariate model, including both imaging and systemic factors. Conclusion: With standard imaging techniques and ways of processing images rapidly evolving, an international network of centers is needed to routinely capture systemic health factors simultaneously to retinal images so that gains in prediction increment may be precisely quantified to determine the usefulness of various health factors in the prognosis of DRD and prediction of response to treatment. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Towards zoomable multidimensional maps of the cell.

The detailed structure of molecular networks, including their dependence on conditions and time, are now routinely assayed by various experimental techniques. Visualization is a vital aid in integrating and interpreting such data. We describe emerging approaches for representing and visualizing systems data and for achieving semantic zooming, or changes in information density concordant with scale. A central challenge is to move beyond the display of a static network to visualizations of networks as a function of time, space and cell state, which capture the adaptability of the cell. We consider approaches for representing the role of protein complexes in the cell cycle, displaying modules of metabolism in a hierarchical format, integrating experimental interaction data with structured vocabularies such as Gene Ontology categories and representing conserved interactions among orthologous groups of genes.

VisANT 3.0: new modules for pathway visualization, editing, prediction and construction.

With the integration of the KEGG and Predictome databases as well as two search engines for coexpressed genes/proteins using data sets obtained from the Stanford Microarray Database (SMD) and Gene Expression Omnibus (GEO) database, VisANT 3.0 supports exploratory pathway analysis, which includes multi-scale visualization of multiple pathways, editing and annotating pathways using a KEGG compatible visual notation and visualization of expression data in the context of pathways. Expression levels are represented either by color intensity or by nodes with an embedded expression profile. Multiple experiments can be navigated or animated. Known KEGG pathways can be enriched by querying either coexpressed components of known pathway members or proteins with known physical interactions. Predicted pathways for genes/proteins with unknown functions can be inferred from coexpression or physical interaction data. Pathways produced in VisANT can be saved as computer-readable XML format (VisML), graphic images or high-resolution Scalable Vector Graphics (SVG). Pathways in the format of VisML can be securely shared within an interested group or published online using a simple Web link. VisANT is freely available at http://visant.bu.edu.

An equilibrium partitioning model connecting gene expression and cis-motif content.

Thermodynamic favorability of transcription factor (TF) binding to DNA is a significant factor in the control of gene expression. Theoretical and in vitro measures link the relative equilibrium energy of a particular DNA binding protein to the sequence variation among binding sites in a genome. Extending this principle, we investigate whether biological variation in expression levels of active proteins leads to regulation of different sets of genes, based on inferred affinities of sites upstream of those genes. The TF-concentration-dependent variation in the repertoire of genes regulated by a particular TF is expected to follow patterns of chemical partitioning over DNA sites having differing affinity, and we develop a new modeling approach to test this hypothesis. Based on computational TF binding site discovery and genome-wide expression data available in Saccharomyces cerevisiae, we explore motif content for sets of genes and conditions having varying concentrations of different transcription factors which turn those genes on or off. We find cases of significant correlation between the level of intragenomic motif sequence variation and modeled TF protein levels that actuates regulation of corresponding sets of genes, and discuss the observed TF motif variants for several yeast transcription factors, as well as the potential biological functions of genes that are regulated by differential response to these high and low concentrations of particular TFs. These findings suggest that motif sequences of transcription factor binding sites may often be linked with the expression state of corresponding DNA-binding proteins.

VisANT: data-integrating visual framework for biological networks and modules.

VisANT is a web-based software framework for visualizing and analyzing many types of networks of biological interactions and associations. Networks are a useful computational tool for representing many types of biological data, such as biomolecular interactions, cellular pathways and functional modules. Given user-defined sets of interactions or groupings between genes or proteins, VisANT provides: (i) a visual interface for combining and annotating network data, (ii) supporting function and annotation data for different genomes from the Gene Ontology and KEGG databases and (iii) the statistical and analytical tools needed for extracting topological properties of the user-defined networks. Users can customize, modify, save and share network views with other users, and import basic network data representations from their own data sources, and from standard exchange formats such as PSI-MI and BioPAX. The software framework we employ also supports the development of more sophisticated visualization and analysis functions through its open API for Java-based plug-ins. VisANT is distributed freely via the web at http://visant.bu.edu and can also be downloaded for individual use.

The interaction map of yeast: terra incognita?

A systematic curation of the literature on Saccharomyces cerevisiae has yielded a comprehensive collection of experimentally observed interactions. This new resource augments current views of the topological structure of yeast's physical and genetic networks, but also reveals that existing studies cover only a fraction of the cell.