GeneSrF and varSelRF: a web-based tool and R package for gene selection and classification using random forest

<p>Abstract</p> <p>Background</p> <p>Microarray data are often used for patient classification and gene selection. An appropriate tool for end users and biomedical researchers should combine user friendliness with statistical rigor, including carefully avoiding selection biases and allowing analysis of multiple solutions, together with access to additional functional information of selected genes. Methodologically, such a tool would be of greater use if it incorporates state-of-the-art computational approaches and makes source code available.</p> <p>Results</p> <p>We have developed GeneSrF, a web-based tool, and varSelRF, an R package, that implement, in the context of patient classification, a validated method for selecting very small sets of genes while preserving classification accuracy. Computation is parallelized, allowing to take advantage of multicore CPUs and clusters of workstations. Output includes bootstrapped estimates of prediction error rate, and assessments of the stability of the solutions. Clickable tables link to additional information for each gene (GO terms, PubMed citations, KEGG pathways), and output can be sent to PaLS for examination of PubMed references, GO terms, KEGG and and Reactome pathways characteristic of sets of genes selected for class prediction. The full source code is available, allowing to extend the software. The web-based application is available from <url>http://genesrf2.bioinfo.cnio.es</url>. All source code is available from Bioinformatics.org or The Launchpad. The R package is also available from CRAN.</p> <p>Conclusion</p> <p>varSelRF and GeneSrF implement a validated method for gene selection including bootstrap estimates of classification error rate. They are valuable tools for applied biomedical researchers, specially for exploratory work with microarray data. Because of the underlying technology used (combination of parallelization with web-based application) they are also of methodological interest to bioinformaticians and biostatisticians.</p

Training evaluation: a case study of training Iranian health managers

<p>Abstract</p> <p>Background</p> <p>The Ministry of Health and Medical Education in the Islamic Republic of Iran has undertaken a reform of its health system, in which-lower level managers are given new roles and responsibilities in a decentralized system. To support these efforts, a United Kingdom-based university was contracted by the World Health Organization to design a series of courses for health managers and trainers. This process was also intended to develop the capacity of the National Public Health Management Centre in Tabriz, Iran, to enable it to organize relevant short courses in health management on a continuing basis. A total of seven short training courses were implemented, three in the United Kingdom and four in Tabriz, with 35 participants. A detailed evaluation of the courses was undertaken to guide future development of the training programmes.</p> <p>Methods</p> <p>The Kirkpatrick framework for evaluation of training was used to measure participants' reactions, learning, application to the job, and to a lesser extent, organizational impact. Particular emphasis was put on application of learning to the participants' job. A structured questionnaire was administered to 23 participants, out of 35, between one and 13 months after they had attended the courses. Respondents, like the training course participants, were predominantly from provincial universities, with both health system and academic responsibilities. Interviews with key informants and ex-trainees provided supplemental information, especially on organizational impact.</p> <p>Results</p> <p>Participants' preferred interactive methods for learning about health planning and management. They found the course content to be relevant, but with an overemphasis on theory compared to practical, locally-specific information. In terms of application of learning to their jobs, participants found specific information and skills to be most useful, such as health systems research and group work/problem solving. The least useful areas were those that dealt with training and leadership. Participants reported little difficulty in applying learning deemed "useful", and had applied it often. In general, a learning area was used less when it was found difficult to apply, with a few exceptions, such as problem-solving. Four fifths of respondents claimed they could perform their jobs better because of new skills and more in-depth understanding of health systems, and one third had been asked to train their colleagues, indicating a potential for impact on their organization. Interviews with key informants indicated that job performance of trainees had improved.</p> <p>Conclusion</p> <p>The health management training programmes in Iran, and the external university involved in capacity building, benefited from following basic principles of good training practice, which incorporated needs assessment, selection of participants and definition of appropriate learning outcomes, course content and methods, along with focused evaluation. Contracts for external assistance should include specific mention of capacity building, and allow for the collaborative development of courses and of evaluation plans, in order to build capacity of local partners throughout the training cycle. This would also help to develop training content that uses material from local health management situations to demonstrate key theories and develop locally required skills. Training evaluations should as a minimum assess participants' reactions and learning for every course. Communication of evaluation results should be designed to ensure that data informs training activities, as well as the health and human resources managers who are investing in the development of their staff.</p

Training for innovation in Spain

The capacity for innovation of an organisation largely depends on its ability to acquire and develop new knowledge. Training is particularly important in this process, as it allows employees to constantly acquire new competences. This study provides a preliminary picture of the situation of training for innovation in Spain, and identifies the characteristics of companies offering training for innovation. Results show that 35.3% of Spanish companies undertake innovation processes and 22.3% offer training related to these innovation processes. For the 82% of these companies training helped the innovation process, so training is an important tool for innovative change

SignS: a parallelized, open-source, freely available, web-based tool for gene selection and molecular signatures for survival and censored data

<p>Abstract</p> <p>Background</p> <p>Censored data are increasingly common in many microarray studies that attempt to relate gene expression to patient survival. Several new methods have been proposed in the last two years. Most of these methods, however, are not available to biomedical researchers, leading to many re-implementations from scratch of ad-hoc, and suboptimal, approaches with survival data.</p> <p>Results</p> <p>We have developed SignS (Signatures for Survival data), an open-source, freely-available, web-based tool and R package for gene selection, building molecular signatures, and prediction with survival data. SignS implements four methods which, according to existing reviews, perform well and, by being of a very different nature, offer complementary approaches. We use parallel computing via MPI, leading to large decreases in user waiting time. Cross-validation is used to asses predictive performance and stability of solutions, the latter an issue of increasing concern given that there are often several solutions with similar predictive performance. Biological interpretation of results is enhanced because genes and signatures in models can be sent to other freely-available on-line tools for examination of PubMed references, GO terms, and KEGG and Reactome pathways of selected genes.</p> <p>Conclusion</p> <p>SignS is the first web-based tool for survival analysis of expression data, and one of the very few with biomedical researchers as target users. SignS is also one of the few bioinformatics web-based applications to extensively use parallelization, including fault tolerance and crash recovery. Because of its combination of methods implemented, usage of parallel computing, code availability, and links to additional data bases, SignS is a unique tool, and will be of immediate relevance to biomedical researchers, biostatisticians and bioinformaticians.</p

Multidentate Terephthalamidate and Hydroxypyridonate Ligands: Towards New Orally Active Chelators

The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using {sup 59}Fe, {sup 238}Pu, and {sup 241}Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents [deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides] and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference