Reproducibility of microarray data: a further analysis of microarray quality control (MAQC) data

<p>Abstract</p> <p>Background</p> <p>Many researchers are concerned with the comparability and reliability of microarray gene expression data. Recent completion of the MicroArray Quality Control (MAQC) project provides a unique opportunity to assess reproducibility across multiple sites and the comparability across multiple platforms. The MAQC analysis presented for the conclusion of inter- and intra-platform comparability/reproducibility of microarray gene expression measurements is inadequate. We evaluate the reproducibility/comparability of the MAQC data for 12901 common genes in four titration samples generated from five high-density one-color microarray platforms and the TaqMan technology. We discuss some of the problems with the use of correlation coefficient as metric to evaluate the inter- and intra-platform reproducibility and the percent of overlapping genes (POG) as a measure for evaluation of a gene selection procedure by MAQC.</p> <p>Results</p> <p>A total of 293 arrays were used in the intra- and inter-platform analysis. A hierarchical cluster analysis shows distinct differences in the measured intensities among the five platforms. A number of genes show a small fold-change in one platform and a large fold-change in another platform, even though the correlations between platforms are high. An analysis of variance shows thirty percent of gene expressions of the samples show inconsistent patterns across the five platforms. We illustrated that POG does not reflect the accuracy of a selected gene list. A non-overlapping gene can be truly differentially expressed with a stringent cut, and an overlapping gene can be non-differentially expressed with non-stringent cutoff. In addition, POG is an unusable selection criterion. POG can increase or decrease irregularly as cutoff changes; there is no criterion to determine a cutoff so that POG is optimized.</p> <p>Conclusion</p> <p>Using various statistical methods we demonstrate that there are differences in the intensities measured by different platforms and different sites within platform. Within each platform, the patterns of expression are generally consistent, but there is site-by-site variability. Evaluation of data analysis methods for use in regulatory decision should take no treatment effect into consideration, when there is no treatment effect, "a fold-change cutoff with a non-stringent p-value cutoff" could result in 100% false positive error selection.</p

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Human and Non-Human Primate Genomes Share Hotspots of Positive Selection

Among primates, genome-wide analysis of recent positive selection is currently limited to the human species because it requires extensive sampling of genotypic data from many individuals. The extent to which genes positively selected in human also present adaptive changes in other primates therefore remains unknown. This question is important because a gene that has been positively selected independently in the human and in other primate lineages may be less likely to be involved in human specific phenotypic changes such as dietary habits or cognitive abilities. To answer this question, we analysed heterozygous Single Nucleotide Polymorphisms (SNPs) in the genomes of single human, chimpanzee, orangutan, and macaque individuals using a new method aiming to identify selective sweeps genome-wide. We found an unexpectedly high number of orthologous genes exhibiting signatures of a selective sweep simultaneously in several primate species, suggesting the presence of hotspots of positive selection. A similar significant excess is evident when comparing genes positively selected during recent human evolution with genes subjected to positive selection in their coding sequence in other primate lineages and identified using a different test. These findings are further supported by comparing several published human genome scans for positive selection with our findings in non-human primate genomes. We thus provide extensive evidence that the co-occurrence of positive selection in humans and in other primates at the same genetic loci can be measured with only four species, an indication that it may be a widespread phenomenon. The identification of positive selection in humans alongside other primates is a powerful tool to outline those genes that were selected uniquely during recent human evolution

An economic appraisal of the Australian Medical Sheepskin for the prevention of sacral pressure ulcers from a nursing home perspective

<p>Abstract</p> <p>Background</p> <p>Many devices are in use to prevent pressure ulcers, but from most little is known about their effects and costs. One such preventive device is the Australian Medical Sheepskin that has been proven effective in three randomized trials. In this study the costs and savings from the use of the Australian Medical Sheepskin were investigated from the perspective of a nursing home.</p> <p>Methods</p> <p>An economic model was developed in which monetary costs and monetary savings in respect of the sheepskin were balanced against each other. The model was applied to a fictional (Dutch) nursing home with 100 beds for rehabilitation patients and a time horizon of one year. Input variables for the model consisted of investment costs for using the sheepskin (purchase and laundry), and savings through the prevented cases of pressure ulcers. The input values for the investment costs and for the effectiveness were empirically based on a trial with newly admitted rehabilitation patients from eight nursing homes. The input values for the costs of pressure ulcer treatment were estimated by means of four different approaches.</p> <p>Results</p> <p>Investment costs for using the Australian Medical Sheepskin were larger than the monetary savings obtained by preventing pressure ulcers. Use of the Australian Medical Sheepskin involves an additional cost of approximately €2 per patient per day. Preventing one case of a sacral pressure ulcer by means of the Australian Medical Sheepskin involves an investment of €2,974 when the sheepskin is given to all patients. When the sheepskin is selectively used for more critical patients only, the investment to prevent one case of sacral pressure ulcers decreases to €2,479 (pressure ulcer risk patients) or €1,847 (ADL-severely impaired patients). The factors with the strongest influence on the balance are the frequency of changing the sheepskin and the costs of washing related to this. The economic model was hampered by considerable uncertainty in the estimations of the costs of pressure ulcer treatment.</p> <p>Conclusions</p> <p>From a nursing home perspective, the investment costs for use of the Australian Medical Sheepskin in newly admitted rehabilitation patients are larger than the monetary savings obtained by preventing pressure ulcers.</p

Cytokine Combination Therapy with Erythropoietin and Granulocyte Colony Stimulating Factor in a Porcine Model of Acute Myocardial Infarction

PurposeErythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model.MethodsMI was induced in pigs by a 90&nbsp;min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6&nbsp;weeks post-MI. Histopathology was performed 6&nbsp;weeks post-MI.ResultsAt week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41 ± 1% vs. 33 ± 1%, p &lt; 0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy.ConclusionOur findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF

Design and Deploying Tools to ‘Actively Engaging Nature’: The My Naturewatch Project as an Agent for Engagement

‘Shifting Baseline Syndrome’ is highly apparent in the context of generational shifts in work and life patterns that reduce interaction with and knowledge of the natural world, and therefore expectations of it. This is exacerbated by changes in the natural world itself due to climate change, biodiversity decline and a range of anthropogenic factors. Distributed and accessible technologies, and grass roots approaches provide fresh opportunities for interactions, which enable active engagement in ecological scenarios. The My NatureWatch project uses digital devices to collect visual content about UK wildlife, promoting ‘active engagements with nature’. The project embodies Inclusive Design in the Digital Age, as the activity; engages a wide demographic community, can be used by all, provided user led agency and produced methodological design lessons. The article frames My Naturewatch as an agent for active designed engagements with nature. The research objective is to comprehend ‘how to design tools for positive nature engagement’ holding value for; (1) academic communities as validated methodologies (2) the public through access to enabling technologies, content and knowledge (3) industry in the form of new; experiences, engagements and commerce. The approach is specifically designed to yield insights from a multitude of engagements, through the deployment of accessible, lowcost products. Project reporting documents the benefits, pitfalls and opportunities in the aforementioned engagement uncovered through design-led approaches. Insights are gathered from public/community facing workshops, wildlife experts, ecologists, economists, educators and wildlife NGO’s. The engagement methodologies are compared highlighting which initiative yielded ‘Active Engagement with Nature’

Skin Regeneration in Adult Axolotls: A Blueprint for Scar-Free Healing in Vertebrates

While considerable progress has been made towards understanding the complex processes and pathways that regulate human wound healing, regenerative medicine has been unable to develop therapies that coax the natural wound environment to heal scar-free. The inability to induce perfect skin regeneration stems partly from our limited understanding of how scar-free healing occurs in a natural setting. Here we have investigated the wound repair process in adult axolotls and demonstrate that they are capable of perfectly repairing full thickness excisional wounds made on the flank. In the context of mammalian wound repair, our findings reveal a substantial reduction in hemostasis, reduced neutrophil infiltration and a relatively long delay in production of new extracellular matrix (ECM) during scar-free healing. Additionally, we test the hypothesis that metamorphosis leads to scarring and instead show that terrestrial axolotls also heal scar-free, albeit at a slower rate. Analysis of newly forming dermal ECM suggests that low levels of fibronectin and high levels of tenascin-C promote regeneration in lieu of scarring. Lastly, a genetic analysis during wound healing comparing epidermis between aquatic and terrestrial axolotls suggests that matrix metalloproteinases may regulate the fibrotic response. Our findings outline a blueprint to understand the cellular and molecular mechanisms coordinating scar-free healing that will be useful towards elucidating new regenerative therapies targeting fibrosis and wound repair