Robust test method for time-course microarray experiments.

BACKGROUND: In a time-course microarray experiment, the expression level for each gene is observed across a number of time-points in order to characterize the temporal trajectories of the gene-expression profiles. For many of these experiments, the scientific aim is the identification of genes for which the trajectories depend on an experimental or phenotypic factor. There is an extensive recent body of literature on statistical methodology for addressing this analytical problem. Most of the existing methods are based on estimating the time-course trajectories using parametric or non-parametric mean regression methods. The sensitivity of these regression methods to outliers, an issue that is well documented in the statistical literature, should be of concern when analyzing microarray data. RESULTS: In this paper, we propose a robust testing method for identifying genes whose expression time profiles depend on a factor. Furthermore, we propose a multiple testing procedure to adjust for multiplicity. CONCLUSIONS: Through an extensive simulation study, we will illustrate the performance of our method. Finally, we will report the results from applying our method to a case study and discussing potential extensions.

WriteSim TCExam--an open source text simulation environment for training novice researchers in scientific writing.

BACKGROUND: The ability to write clearly and effectively is of central importance to the scientific enterprise. Encouraged by the success of simulation environments in other biomedical sciences, we developed WriteSim TCExam, an open-source, Web-based, textual simulation environment for teaching effective writing techniques to novice researchers. We shortlisted and modified an existing open source application - TCExam to serve as a textual simulation environment. After testing usability internally in our team, we conducted formal field usability studies with novice researchers. These were followed by formal surveys with researchers fitting the role of administrators and users (novice researchers) RESULTS: The development process was guided by feedback from usability tests within our research team. Online surveys and formal studies, involving members of the Research on Research group and selected novice researchers, show that the application is user-friendly. Additionally it has been used to train 25 novice researchers in scientific writing to date and has generated encouraging results. CONCLUSION: WriteSim TCExam is the first Web-based, open-source textual simulation environment designed to complement traditional scientific writing instruction. While initial reviews by students and educators have been positive, a formal study is needed to measure its benefits in comparison to standard instructional methods.

Scientific writing: a randomized controlled trial comparing standard and on-line instruction.

BACKGROUND: Writing plays a central role in the communication of scientific ideas and is therefore a key aspect in researcher education, ultimately determining the success and long-term sustainability of their careers. Despite the growing popularity of e-learning, we are not aware of any existing study comparing on-line vs. traditional classroom-based methods for teaching scientific writing. METHODS: Forty eight participants from a medical, nursing and physiotherapy background from US and Brazil were randomly assigned to two groups (n = 24 per group): An on-line writing workshop group (on-line group), in which participants used virtual communication, google docs and standard writing templates, and a standard writing guidance training (standard group) where participants received standard instruction without the aid of virtual communication and writing templates. Two outcomes, manuscript quality was assessed using the scores obtained in Six subgroup analysis scale as the primary outcome measure, and satisfaction scores with Likert scale were evaluated. To control for observer variability, inter-observer reliability was assessed using Fleiss's kappa. A post-hoc analysis comparing rates of communication between mentors and participants was performed. Nonparametric tests were used to assess intervention efficacy. RESULTS: Excellent inter-observer reliability among three reviewers was found, with an Intraclass Correlation Coefficient (ICC) agreement = 0.931882 and ICC consistency = 0.932485. On-line group had better overall manuscript quality (p = 0.0017, SSQSavg score 75.3 +/- 14.21, ranging from 37 to 94) compared to the standard group (47.27 +/- 14.64, ranging from 20 to 72). Participant satisfaction was higher in the on-line group (4.3 +/- 0.73) compared to the standard group (3.09 +/- 1.11) (p = 0.001). The standard group also had fewer communication events compared to the on-line group (0.91 +/- 0.81 vs. 2.05 +/- 1.23; p = 0.0219). CONCLUSION: Our protocol for on-line scientific writing instruction is better than standard face-to-face instruction in terms of writing quality and student satisfaction. Future studies should evaluate the protocol efficacy in larger longitudinal cohorts involving participants from different languages.

Consistency of financial interest disclosures in the biomedical literature: the case of coronary stents.

BACKGROUND: Disclosure of authors' financial interests has been proposed as a strategy for protecting the integrity of the biomedical literature. We examined whether authors' financial interests were disclosed consistently in articles on coronary stents published in 2006. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed for English-language articles published in 2006 that provided evidence or guidance regarding the use of coronary artery stents. We recorded article characteristics, including information about authors' financial disclosures. The main outcome measures were the prevalence, nature, and consistency of financial disclosures. There were 746 articles, 2985 authors, and 135 journals in the database. Eighty-three percent of the articles did not contain disclosure statements for any author (including declarations of no interests). Only 6% of authors had an article with a disclosure statement. In comparisons between articles by the same author, the types of disagreement were as follows: no disclosure statements vs declarations of no interests (64%); specific disclosures vs no disclosure statements (34%); and specific disclosures vs declarations of no interests (2%). Among the 75 authors who disclosed at least 1 relationship with an organization, there were 2 cases (3%) in which the organization was disclosed in every article the author wrote. CONCLUSIONS/SIGNIFICANCE: In the rare instances when financial interests were disclosed, they were not disclosed consistently, suggesting that there are problems with transparency in an area of the literature that has important implications for patient care. Our findings suggest that the inconsistencies we observed are due to both the policies of journals and the behavior of some authors.

The toxicology of climate change: environmental contaminants in a warming world.

Climate change induced by anthropogenic warming of the earth's atmosphere is a daunting problem. This review examines one of the consequences of climate change that has only recently attracted attention: namely, the effects of climate change on the environmental distribution and toxicity of chemical pollutants. A review was undertaken of the scientific literature (original research articles, reviews, government and intergovernmental reports) focusing on the interactions of toxicants with the environmental parameters, temperature, precipitation, and salinity, as altered by climate change. Three broad classes of chemical toxicants of global significance were the focus: air pollutants, persistent organic pollutants (POPs), including some organochlorine pesticides, and other classes of pesticides. Generally, increases in temperature will enhance the toxicity of contaminants and increase concentrations of tropospheric ozone regionally, but will also likely increase rates of chemical degradation. While further research is needed, climate change coupled with air pollutant exposures may have potentially serious adverse consequences for human health in urban and polluted regions. Climate change producing alterations in: food webs, lipid dynamics, ice and snow melt, and organic carbon cycling could result in increased POP levels in water, soil, and biota. There is also compelling evidence that increasing temperatures could be deleterious to pollutant-exposed wildlife. For example, elevated water temperatures may alter the biotransformation of contaminants to more bioactive metabolites and impair homeostasis. The complex interactions between climate change and pollutants may be particularly problematic for species living at the edge of their physiological tolerance range where acclimation capacity may be limited. In addition to temperature increases, regional precipitation patterns are projected to be altered with climate change. Regions subject to decreases in precipitation may experience enhanced volatilization of POPs and pesticides to the atmosphere. Reduced precipitation will also increase air pollution in urbanized regions resulting in negative health effects, which may be exacerbated by temperature increases. Regions subject to increased precipitation will have lower levels of air pollution, but will likely experience enhanced surface deposition of airborne POPs and increased run-off of pesticides. Moreover, increases in the intensity and frequency of storm events linked to climate change could lead to more severe episodes of chemical contamination of water bodies and surrounding watersheds. Changes in salinity may affect aquatic organisms as an independent stressor as well as by altering the bioavailability and in some instances increasing the toxicity of chemicals. A paramount issue will be to identify species and populations especially vulnerable to climate-pollutant interactions, in the context of the many other physical, chemical, and biological stressors that will be altered with climate change. Moreover, it will be important to predict tipping points that might trigger or accelerate synergistic interactions between climate change and contaminant exposures.

Development of a decision aid to inform patients' and families' renal replacement therapy selection decisions.

BACKGROUND: Few educational resources have been developed to inform patients' renal replacement therapy (RRT) selection decisions. Patients progressing toward end stage renal disease (ESRD) must decide among multiple treatment options with varying characteristics. Complex information about treatments must be adequately conveyed to patients with different educational backgrounds and informational needs. Decisions about treatment options also require family input, as families often participate in patients' treatment and support patients' decisions. We describe the development, design, and preliminary evaluation of an informational, evidence-based, and patient-and family-centered decision aid for patients with ESRD and varying levels of health literacy, health numeracy, and cognitive function. METHODS: We designed a decision aid comprising a complementary video and informational handbook. We based our development process on data previously obtained from qualitative focus groups and systematic literature reviews. We simultaneously developed the video and handbook in "stages." For the video, stages included (1) directed interviews with culturally appropriate patients and families and preliminary script development, (2) video production, and (3) screening the video with patients and their families. For the handbook, stages comprised (1) preliminary content design, (2) a mixed-methods pilot study among diverse patients to assess comprehension of handbook material, and (3) screening the handbook with patients and their families. RESULTS: The video and handbook both addressed potential benefits and trade-offs of treatment selections. The 50-minute video consisted of demographically diverse patients and their families describing their positive and negative experiences with selecting a treatment option. The video also incorporated health professionals' testimonials regarding various considerations that might influence patients' and families' treatment selections. The handbook was comprised of written words, pictures of patients and health care providers, and diagrams describing the findings and quality of scientific studies comparing treatments. The handbook text was written at a 4th to 6th grade reading level. Pilot study results demonstrated that a majority of patients could understand information presented in the handbook. Patient and families screening the nearly completed video and handbook reviewed the materials favorably. CONCLUSIONS: This rigorously designed decision aid may help patients and families make informed decisions about their treatment options for RRT that are well aligned with their values.

Clinical Research Environment in India: Challenges and Proposed Solutions.

India has compelling need and keen aspirations for indigenous clinical research. Notwithstanding this need and previously reported growth the expected expansion of Indian clinical research has not materialized. We reviewed the scientific literature, lay press reports, and ClinicalTrials.gov data for information and commentary on projections, progress, and impediments associated with clinical trials in India. We also propose targeted solutions to identified challenges. The Indian clinical trial sector grew by (+) 20.3% CAGR (compound annual growth rate) between 2005 and 2010 and contracted by (-) 14.6% CAGR between 2010 and 2013. Phase-1 trials grew by (+) 43.5% CAGR from 2005-2013, phase-2 trials grew by (+) 19.8% CAGR from 2005-2009 and contracted by (-) 12.6% CAGR from 2009-2013, and phase-3 trials grew by (+) 13.0% CAGR from 2005-2010 and contracted by (-) 28.8% CAGR from 2010-2013. This was associated with a slowing of the regulatory approval process, increased media coverage and activist engagement, and accelerated development of regulatory guidelines and recuperative initiatives. We propose the following as potential targets for restorative interventions: Regulatory overhaul (leadership and enforcement of regulations, resolution of ambiguity in regulations, staffing, training, guidelines, and ethical principles [e.g., compensation]).Education and training of research professionals, clinicians, and regulators.Public awareness and empowerment. After a peak in 2009-2010, the clinical research sector in India appears to be experiencing a contraction. There are indications of challenges in regulatory enforcement of guidelines; training of clinical research professionals; and awareness, participation, partnership, and the general image amongst the non-professional media and public. Preventative and corrective principles and interventions are outlined with the goal of realizing the clinical research potential in India.

Evolutionary characters, phenotypes and ontologies: curating data from the systematic biology literature.

BACKGROUND: The wealth of phenotypic descriptions documented in the published articles, monographs, and dissertations of phylogenetic systematics is traditionally reported in a free-text format, and it is therefore largely inaccessible for linkage to biological databases for genetics, development, and phenotypes, and difficult to manage for large-scale integrative work. The Phenoscape project aims to represent these complex and detailed descriptions with rich and formal semantics that are amenable to computation and integration with phenotype data from other fields of biology. This entails reconceptualizing the traditional free-text characters into the computable Entity-Quality (EQ) formalism using ontologies. METHODOLOGY/PRINCIPAL FINDINGS: We used ontologies and the EQ formalism to curate a collection of 47 phylogenetic studies on ostariophysan fishes (including catfishes, characins, minnows, knifefishes) and their relatives with the goal of integrating these complex phenotype descriptions with information from an existing model organism database (zebrafish, http://zfin.org). We developed a curation workflow for the collection of character, taxonomic and specimen data from these publications. A total of 4,617 phenotypic characters (10,512 states) for 3,449 taxa, primarily species, were curated into EQ formalism (for a total of 12,861 EQ statements) using anatomical and taxonomic terms from teleost-specific ontologies (Teleost Anatomy Ontology and Teleost Taxonomy Ontology) in combination with terms from a quality ontology (Phenotype and Trait Ontology). Standards and guidelines for consistently and accurately representing phenotypes were developed in response to the challenges that were evident from two annotation experiments and from feedback from curators. CONCLUSIONS/SIGNIFICANCE: The challenges we encountered and many of the curation standards and methods for improving consistency that we developed are generally applicable to any effort to represent phenotypes using ontologies. This is because an ontological representation of the detailed variations in phenotype, whether between mutant or wildtype, among individual humans, or across the diversity of species, requires a process by which a precise combination of terms from domain ontologies are selected and organized according to logical relations. The efficiencies that we have developed in this process will be useful for any attempt to annotate complex phenotypic descriptions using ontologies. We also discuss some ramifications of EQ representation for the domain of systematics.

Developing Quantitative Methodologies for the Digital Humanities: A Case Study of 20th Century American Commentary on Russian Literature

Using scientific methods in the humanities is at the forefront of objective literary analysis. However, processing big data is particularly complex when the subject matter is qualitative rather than numerical. Large volumes of text require specialized tools to produce quantifiable data from ideas and sentiments. Our team researched the extent to which tools such as Weka and MALLET can test hypotheses about qualitative information. We examined the claim that literary commentary exists within political environments and used US periodical articles concerning Russian literature in the early twentieth century as a case study. These tools generated useful quantitative data that allowed us to run stepwise binary logistic regressions. These statistical tests allowed for time series experiments using sea change and emergency models of history, as well as classification experiments with regard to author characteristics, social issues, and sentiment expressed. Both types of experiments supported our claim with varying degrees, but more importantly served as a definitive demonstration that digitally enhanced quantitative forms of analysis can apply to qualitative data. Our findings set the foundation for further experiments in the emerging field of digital humanities.

Using an interactive software environment for the parallelization of real-world scientific applications

The parallelization of real-world compute intensive Fortran application codes is generally not a trivial task. If the time to complete the parallelization is to be significantly reduced then an environment is needed that will assist the programmer in the various tasks of code parallelization. In this paper the authors present a code parallelization environment where a number of tools that address the main tasks such as code parallelization, debugging and optimization are available. The ParaWise and CAPO parallelization tools are discussed which enable the near automatic parallelization of real-world scientific application codes for shared and distributed memory-based parallel systems. As user involvement in the parallelization process can introduce errors, a relative debugging tool (P2d2) is also available and can be used to perform nearly automatic relative debugging of a program that has been parallelized using the tools. A high quality interprocedural dependence analysis as well as user-tool interaction are also highlighted and are vital to the generation of efficient parallel code and in the optimization of the backtracking and speculation process used in relative debugging. Results of benchmark and real-world application codes parallelized are presented and show the benefits of using the environment

Nursing resources and patient outcomes in intensive care: a systematic review of the literature

Objectives: To evaluate the empirical evidence linking nursing resources to patient outcomes in intensive care settings as a framework for future research in this area. Background: Concerns about patient safely and the quality of care are driving research on the clinical and cost-effectiveness of health care interventions, including the deployment of human resources. This is particularly important in intensive care where a large proportion of the health care budget is consumed and where nursing staff is the main item of expenditure. Recommendations about staffing levels have been trade but may not be evidence based and may not always be achieved in practice. Methods: We searched systematically for studies of the impact of nursing resources (e.g. nurse-patient ratios, nurses' level of education, training and experience) on patient Outcomes, including mortality and adverse events, in adult intensive care. Abstracts of articles were reviewed and retrieved if they investigated the relationship between nursing resources and patient Outcomes. Characteristics of the studies were tabulated and the quality of the Studies assessed. Results: Of the 15 studies included in this review, two reported it statistical relationship between nursing resources and both mortality and adverse events, one reported ail association to mortality only, seven studies reported that they Could not reject the null hypothesis of no relationship to mortality and 10 studies (out of 10 that tested the hypothesis) reported a relationship to adverse events. The main explanatory mechanisms were the lack of time for nurses to perform preventative measures, or for patient surveillance. The nurses' role in pain control was noted by One author. Studies were mainly observational and retrospective and varied in scope from 1 to 52 units. Recommendations for future research include developing the mechanisms linking nursing resources to patient Outcomes, and designing large multi-centre prospective Studies that link patient's exposure to nursing care oil a shift-by-shift basis over time. (C) 2007 Elsevier Ltd. All rights reserved.

Literature and the shaman: Jung, trauma stories and new origin stories in The Lion, the witch and the wardrobe by C.S. Lewis

The paper first considers the role of Jungian ideas in relation to academic disciplines and to literary studies in particular. Jung is a significant resource in negotiating developments in literary theory because of his characteristic treatment of the ‘other’. The paper then looks at The Lion, the Witch and the Wardrobe (1950) by C.S. Lewis whose own construction of archetypes is very close to Jung’s. By drawing upon new post-Jungian work from Jerome Bernstein’s Living in the Borderland (2005), the novel is revealed to be intimately concerned with narratives of trauma and of origin. Indeed, a Jungian and post-Jungian approach is able to situate the text both within nature and in the historical traumas of war as well as the personal traumas of subjectivity. Where Bernstein connects his work to the postcolonial ethos of the modern Navajo shaman, this new weaving of literary and cultural theory points to the residue of shamanism within the arts of the West. [From the Publisher]