An economic appraisal of lower extremity bypass graft maintenance

AbstractObjective: Infrainguinal graft surveillance leads to intervention on the basis of duplex-identified stenoses. We have become increasingly concerned about the high frequency with which such revisions are required to maximize graft patency and limb salvage rates. The economic implications of these procedures have not been carefully analyzed or justified. Methods: We retrospectively reviewed 155 consecutive autogenous infrainguinal bypass grafts performed for chronic leg ischemia in 141 patients. All patients were enrolled in a prospective surveillance program using color flow duplex imaging. Full economic appraisal (cost analysis, cost-effect analysis, and cost-benefit analysis) was performed for all graft surveillance and limb salvage–related interventions through use of standard accounting and valuation techniques. Results: Mean follow-up was 27 months. Five-year assisted primary patency (72%) and limb salvage rates (91%) were calculated by means of life table analysis. A total of 61 grafts required 86 revisions. Within 1 year of implantation, 36% of the grafts required revision. During this first year, the mean cost per graft enrolled was $9417. Time intervals after the initial year demonstrated a reduced annual revision rate (6$1725 per graft). The mean 5-year cost of graft maintenance ($16,318) approached that of the initial bypass graft ($19,331). The sum of the initial cost of bypass graft and 5-year graft maintenance cost ($35,649) was similar to the cost of amputation ($36,273). Grafts revised for duplex-detected stenoses (n = 46), in comparison with those revised after thrombosis (n = 15), had an improved 1-year patency (93% vs 57%; P <.01), required fewer amputations (2% vs 33%; P <.01), less frequently required multiple graft revisions (P =.06), and generated fewer expenses (at 12 months after revision, $17,688 vs$45,252, P <.01). Conclusion: The cost associated with graft maintenance is significant, particularly within the first year, and demands consideration. Revision of a duplex-identified stenosis was significantly less costly than revision after graft thrombosis. Compared with the cost of limb amputation, limb salvage–related expenses appear to be justified. (J Vasc Surg 2000;32:1-12.

Discovery with Models: A Case Study on Carelessness in Computer-based Science Inquiry

In recent years, an increasing number of analyses in Learning Analytics and Educational Data Mining (EDM) have adopted a &quot;Discovery with Models&quot; approach, where an existing model is used as a key component in a new EDM/analytics analysis. This article presents a theoretical discussion on the emergence of discovery with models, its potential to enhance research on learning and learners, and key lessons learned in how discovery with models can be conducted validly and effectively. We illustrate these issues through discussion of a case study where discovery with models was used to investigate a form of disengaged behavior, i.e., carelessness, in the context of middle school computer-based science inquiry. This behavior has been acknowledged as a problem in education as early as the 1920s. With the increasing use of high-stakes testing, the cost of student carelessness can be higher. For instance, within computer-based learning environments careless errors can result in reduced educational effectiveness, with students continuing to receive material they have already mastered. Despite the importance of this problem, it has received minimal research attention, in part due to difficulties in operationalizing carelessness as a construct. Building from theory on carelessness and a Bayesian framework for knowledge modeling, we use machine-learned detectors to predict carelessness within authentic use of a computer-based learning environment. We then use a discovery with models approach to link these validated carelessness measures to survey data, to study the correlations between the prevalence of carelessness and student goal orientation. The second construct, carelessness, refers to incorrect answers given by a student on material that the student should be able to answer correctly Rodriguez-Fornells &amp; Maydeu-Olivares, 2000). The application of discovery with models involves two main phases. First, a model of a construct is developed using machine learning or knowledge engineering techniques, and is then validated, as discussed below. Second, this validated model is applied to data and used as a component in another analysis: For example, for identifying outliers through model predictions; examining which variables best predict the modeled construct; finding relationships between the construct and other variables using correlations, predictions, associations rules, causal relationships or other methods; or studying the contexts where the construct occurs, including its prevalence across domains, systems, or populations. For example, in One essential question to pose prior to a discovery with model analysis is whether the model adopted is valid, both overall, and for the specific situation in which it is being used. Ideally, a model should be validated using an approach such as cross-validation, where the model is repeatedly trained on one portion of the data and tested on a different portion, with model predictions compared to appropriate external measures, for example assessments made by humans with acceptably high inter-rater reliability, such as field observations of student behavior for gaming the system (cf. Even after validating in this fashion, validity should be re-considered if the model is used for a substantially different population or context than was used when developing the model.. An alternative approach is to use a simpler knowledge-engineered definition, rationally deriving a function/rule that is then applied to the data. In this case, the model can be inferred to have face validity. However, knowledge-engineered models often DISCOVERY WITH MODELS: A CASE STUDY ON CARELESSNESS 6 produce different results than machine learning-based models, for example in the case of gaming the system. Research studying whether student or content is a better predictor of gaming the system identified different results, depending on which model was applied (cf. Baker, 2007a

The role of the user within the medical device design and development process: medical device manufacturers' perspectives

Copyright @ 2011 Money et al.Background: Academic literature and international standards bodies suggest that user involvement, via the incorporation of human factors engineering methods within the medical device design and development (MDDD) process, offer many benefits that enable the development of safer and more usable medical devices that are better suited to users' needs. However, little research has been carried out to explore medical device manufacturers' beliefs and attitudes towards user involvement within this process, or indeed what value they believe can be added by doing so.Methods: In-depth interviews with representatives from 11 medical device manufacturers are carried out. We ask them to specify who they believe the intended users of the device to be, who they consult to inform the MDDD process, what role they believe the user plays within this process, and what value (if any) they believe users add. Thematic analysis is used to analyse the fully transcribed interview data, to gain insight into medical device manufacturers' beliefs and attitudes towards user involvement within the MDDD process.Results: A number of high-level themes emerged, relating who the user is perceived to be, the methods used, the perceived value and barriers to user involvement, and the nature of user contributions. The findings reveal that despite standards agencies and academic literature offering strong support for the employment formal methods, manufacturers are still hesitant due to a range of factors including: perceived barriers to obtaining ethical approval; the speed at which such activity may be carried out; the belief that there is no need given the 'all-knowing' nature of senior health care staff and clinical champions; a belief that effective results are achievable by consulting a minimal number of champions. Furthermore, less senior health care practitioners and patients were rarely seen as being able to provide valuable input into the process.Conclusions: Medical device manufacturers often do not see the benefit of employing formal human factors engineering methods within the MDDD process. Research is required to better understand the day-to-day requirements of manufacturers within this sector. The development of new or adapted methods may be required if user involvement is to be fully realised.This study was in part funded by grant number Ref: GR/S29874/01 from the Engineering and Physical Sciences Research Council. This article is made available through the Brunel University Open Access Publishing Fund

Time warping of evolutionary distant temporal gene expression data based on noise suppression

<p>Abstract</p> <p>Background</p> <p>Comparative analysis of genome wide temporal gene expression data has a broad potential area of application, including evolutionary biology, developmental biology, and medicine. However, at large evolutionary distances, the construction of global alignments and the consequent comparison of the time-series data are difficult. The main reason is the accumulation of variability in expression profiles of orthologous genes, in the course of evolution.</p> <p>Results</p> <p>We applied Pearson distance matrices, in combination with other noise-suppression techniques and data filtering to improve alignments. This novel framework enhanced the capacity to capture the similarities between the temporal gene expression datasets separated by large evolutionary distances. We aligned and compared the temporal gene expression data in budding (<it>Saccharomyces cerevisiae</it>) and fission (<it>Schizosaccharomyces pombe</it>) yeast, which are separated by more then ~400 myr of evolution. We found that the global alignment (time warping) properly matched the duration of cell cycle phases in these distant organisms, which was measured in prior studies. At the same time, when applied to individual ortholog pairs, this alignment procedure revealed groups of genes with distinct alignments, different from the global alignment.</p> <p>Conclusion</p> <p>Our alignment-based predictions of differences in the cell cycle phases between the two yeast species were in a good agreement with the existing data, thus supporting the computational strategy adopted in this study. We propose that the existence of the alternative alignments, specific to distinct groups of genes, suggests presence of different synchronization modes between the two organisms and possible functional decoupling of particular physiological gene networks in the course of evolution.</p

PathEx: a novel multi factors based datasets selector web tool

<p>Abstract</p> <p>Background</p> <p>Microarray experiments have become very popular in life science research. However, if such experiments are only considered independently, the possibilities for analysis and interpretation of many life science phenomena are reduced. The accumulation of publicly available data provides biomedical researchers with a valuable opportunity to either discover new phenomena or improve the interpretation and validation of other phenomena that partially understood or well known. This can only be achieved by intelligently exploiting this rich mine of information.</p> <p>Description</p> <p>Considering that technologies like microarrays remain prohibitively expensive for researchers with limited means to order their own experimental chips, it would be beneficial to re-use previously published microarray data. For certain researchers interested in finding gene groups (requiring many replicates), there is a great need for tools to help them to select appropriate datasets for analysis. These tools may be effective, if and only if, they are able to re-use previously deposited experiments or to create new experiments not initially envisioned by the depositors. However, the generation of new experiments requires that all published microarray data be completely annotated, which is not currently the case. Thus, we propose the PathEx approach.</p> <p>Conclusion</p> <p>This paper presents PathEx, a human-focused web solution built around a two-component system: one database component, enriched with relevant biological information (expression array, omics data, literature) from different sources, and another component comprising sophisticated web interfaces that allow users to perform complex dataset building queries on the contents integrated into the PathEx database.</p

ProbFAST: Probabilistic Functional Analysis System Tool

<p>Abstract</p> <p>Background</p> <p>The post-genomic era has brought new challenges regarding the understanding of the organization and function of the human genome. Many of these challenges are centered on the meaning of differential gene regulation under distinct biological conditions and can be performed by analyzing the Multiple Differential Expression (MDE) of genes associated with normal and abnormal biological processes. Currently MDE analyses are limited to usual methods of differential expression initially designed for paired analysis.</p> <p>Results</p> <p>We proposed a web platform named ProbFAST for MDE analysis which uses Bayesian inference to identify key genes that are intuitively prioritized by means of probabilities. A simulated study revealed that our method gives a better performance when compared to other approaches and when applied to public expression data, we demonstrated its flexibility to obtain relevant genes biologically associated with normal and abnormal biological processes.</p> <p>Conclusions</p> <p>ProbFAST is a free accessible web-based application that enables MDE analysis on a global scale. It offers an efficient methodological approach for MDE analysis of a set of genes that are turned on and off related to functional information during the evolution of a tumor or tissue differentiation. ProbFAST server can be accessed at <url>http://gdm.fmrp.usp.br/probfast</url>.</p

Stemming Cancer: Functional Genomics of Cancer Stem Cells in Solid Tumors

Cancer stem cells (CSCs) were discovered about 15 years ago in hematopoietic cancers. Subsequently, cancer stem cells were discovered in various solid tumors. Based on parallels with normal stem cells, a developmental process of cancer stem cells follows paths of organized, hierarchical structure of cells with different degrees of maturity. While some investigators have reported particular markers as identification of cancer stem cells, these markers require further research. In this review, we focus on the functional genomics of cancer stem cells. Functional genomics provides useful information on the signaling pathways which are consecutively activated or inactivated amongst those cells. This information is of particular importance for cancer research and clinical treatment in many respects. (1) Understanding of self-renewal mechanisms crucial to tumor growth. (2) Allow the identification of new, more specific marker for CSCs, and (3) pathways that are suitable as future targets for anti-cancer drugs. This is of particular importance, because today’s chemotherapy targets the proliferating cancer cells sparing the relatively slow dividing cancer stem cells. The first step on this long road therefore is to analyze genome-wide expression-profiles within the same type of cancer and then between different types of cancer, encircling those target genes and pathways, which are specific to these cells

Identifying Highly Conserved and Highly Differentiated Gene Ontology Categories in Human Populations

Detecting and interpreting certain system-level characteristics associated with human population genetic differences is a challenge for human geneticists. In this study, we conducted a population genetic study using the HapMap genotype data to identify certain special Gene Ontology (GO) categories associated with high/low genetic difference among 11 Hapmap populations. Initially, the genetic differences in each gene region among these populations were measured using allele frequency, linkage disequilibrium (LD) pattern, and transferability of tagSNPs. The associations between each GO term and these genetic differences were then identified. The results showed that cellular process, catalytic activity, binding, and some of their sub-terms were associated with high levels of genetic difference, and genes involved in these functional categories displayed, on average, high genetic diversity among different populations. By contrast, multicellular organismal processes, molecular transducer activity, and some of their sub-terms were associated with low levels of genetic difference. In particular, the neurological system process under the multicellular organismal process category had low levels of genetic difference; the neurological function also showed high evolutionary conservation between species in some previous studies. These results may provide a new insight into the understanding of human evolutionary history at the system-level

Discovery of Molecular Mechanisms of Traditional Chinese Medicinal Formula Si-Wu-Tang Using Gene Expression Microarray and Connectivity Map

To pursue a systematic approach to discovery of mechanisms of action of traditional Chinese medicine (TCM), we used microarrays, bioinformatics and the “Connectivity Map” (CMAP) to examine TCM-induced changes in gene expression. We demonstrated that this approach can be used to elucidate new molecular targets using a model TCM herbal formula Si-Wu-Tang (SWT) which is widely used for women's health. The human breast cancer MCF-7 cells treated with 0.1 µM estradiol or 2.56 mg/ml of SWT showed dramatic gene expression changes, while no significant change was detected for ferulic acid, a known bioactive compound of SWT. Pathway analysis using differentially expressed genes related to the treatment effect identified that expression of genes in the nuclear factor erythroid 2-related factor 2 (Nrf2) cytoprotective pathway was most significantly affected by SWT, but not by estradiol or ferulic acid. The Nrf2-regulated genes HMOX1, GCLC, GCLM, SLC7A11 and NQO1 were upreguated by SWT in a dose-dependent manner, which was validated by real-time RT-PCR. Consistently, treatment with SWT and its four herbal ingredients resulted in an increased antioxidant response element (ARE)-luciferase reporter activity in MCF-7 and HEK293 cells. Furthermore, the gene expression profile of differentially expressed genes related to SWT treatment was used to compare with those of 1,309 compounds in the CMAP database. The CMAP profiles of estradiol-treated MCF-7 cells showed an excellent match with SWT treatment, consistent with SWT's widely claimed use for women's diseases and indicating a phytoestrogenic effect. The CMAP profiles of chemopreventive agents withaferin A and resveratrol also showed high similarity to the profiles of SWT. This study identified SWT as an Nrf2 activator and phytoestrogen, suggesting its use as a nontoxic chemopreventive agent, and demonstrated the feasibility of combining microarray gene expression profiling with CMAP mining to discover mechanisms of actions and to identify new health benefits of TCMs