Medicine and Health Sciences Commons^™

Ssrn As An Initial Revolution In Academic Knowledge Aggregation And Dissemination, David Bray, Sascha Vitzthum, Benn Konsynski

Sascha Vitzthum

Within this paper we consider our results of using the Social Science Research Network (SSRN) over a period of 18 months to distribute our working papers to the research community. Our experiences have been quite positive, with SSRN serving as a platform both to inform our colleagues about our research as well as inform us about related research (through email and telephoned conversations of colleagues who discovered our paper on SSRN). We then discuss potential future directions for SSRN to consider, and how SSRN might well represent an initial revolution in 21st century academic knowledge aggregation and dissemination. Our paper …

Towards Self-Organizing, Smart Business Networks: Let’S Create ‘Life’ From Inert Information, David Bray, Benn Konsynski

David A. Bray

We review three different theories that can inform how researchers can determine the performance of smart business networks, to include: (1) the Theory of Evolution, (2) the Knowledge-Based Theory of the Firm, and (3) research insights into computers and cognition. We suggest that each of these theories demonstrate that to be generally perceived as smart, an organism needs to be self-organizing, communicative, and tool-making. Consequentially, to determine the performance of a smart business network, we suggest that researchers need to determine the degree to which it is self-organizing, communicative, and tool-making. We then relate these findings to the Internet and …

Fluoranthene, But Not Benzo[A]Pyrene, Interacts With Hypoxia Resulting In Pericardial Effusion And Lordosis In Developing Zebrafish, Cole W. Matson, Alicia R. Timme-Laragy, Richard T. Di Giulio

Alicia R. Timme-Laragy

Previous research has documented several PAHs that interact synergistically, causing severe teratogenicity in developing fish embryos. The coexposure of CYP1A inhibitors (e.g. FL or ANF) with AHR agonists (e.g. BaP or BNF) results in a synergistic increase in toxicity. As with chemical CYP1A inhibitors, it has also been shown that CYP1A morpholinos exacerbate BNF-induced embryotoxicity. We hypothesized that a hypoxia-induced reduction in CYP1A activity in BNF or BaP-exposed zebrafish embryos would similarly enhance pericardial effusion and other developmental abnormalities. BaP, BNF, ANF, and FL exposures, both individually and as BaP+FL or BNF+ANF combinations, were performed under hypoxia and normoxia. CYP1A …

Finding Recurrent Regions Of Copy Number Variation: A Review, Oscar M. Rueda, Ramon Diaz-Uriarte

Ramon Diaz-Uriarte

Copy number alterations (CNA) in genomic DNA are linked to a variety of human diseases. Although many methods have been developed to analyze data from a single subject, disease-critical genes are more likely to be found in regions that are common or recurrent among diseased subjects. Unfortunately, finding recurrent CNA regions remains a challenge. We review existing methods for the identification of recurrent CNA regions. Methods differ in their working definition of ``recurrent region'', the type of input data, the statistical and computational methods used to identify recurrence, and the biological considerations they incorporate (which play a role in the …

Regressing Scalar Outcomes On Image Predictors Via Functional Principal Component Regression, Philip T. Reiss

Philip T. Reiss

No abstract provided.

Survival Unchanged Five Months After Implementing The 2005 Aha Cpr And Ecc Guidelines For Out-Of-Hospital Cardiac Arrest., Blair L. Bigham, Kent M. Koprowicz, John Stouffer, Tom P. Aufderheide, Stuart Donn, Judy Powell, Dan Davis, Sarah Nafziger, Brian Suffoletto, Ahamed Idris, Mike Helbock, Laurie J. Morrison

Kent M Koprowicz

Introduction: To improve survival from out of hospital cardiac arrest (OHCA), the American Heart Association released guidelines in 2005. We examined the effect of these guidelines on survival in the Resuscitation Outcomes Consortium (ROC) Epistry – Cardiac Arrest. We hypothesized that survival would increase after guideline implementation. Methods: 174 EMS agencies from 8 of the 10 ROC sites were surveyed to determine 2005 AHA guideline implementation, or crossover, date. Two sites with 2005 compatible treatment algorithms prior to guideline release were not included. Patients with OHCA secondary to a non cardiac cause, EMS witnessed events, patients <18 years>old, and patients with …

Composite Endpoint Analysis For Assessing Surrogacy With Censored Data, Debashis Ghosh

Debashis Ghosh

Background: There is great interest in the development of surrogate endpoints using new technologies in medical research. The promise of such endpoints is that they would allow for faster completion of clinical trials and would be potentially cost-effective.

Purpose: In determining surrogacy, it is important to distinguish the roles of surrogate from the true endpoint. The latter should be thought of as the gold standard. We discuss a framework in which the utility of a surrogate endpoint is based on whether or not as part of a composite endpoint, it yields treatment effects that associate with that on the true …

Protection Of Retinal Cells From Ischemia By A Novel Gap Junction Inhibitor, Satyabrata Das, Dingo Lin, Snehalata Jena, Aibin Shi, Srinivas Battina, Duy H. Hua, Rachel A. Allbaugh, Dolores J. Takemoto

Rachel A. Allbaugh

Retinal cells which become ischemic will pass apoptotic signal to adjacent cells, resulting in the spread of damage. This occurs through open gap junctions. A class of novel drugs, based on primaquine (PQ), was tested for binding to connexin 43 using simulated docking studies. A novel drug has been synthesized and tested for inhibition of gap junction activity using R28 neuro-retinal cells in culture. Four drugs were initially compared to mefloquine, a known gap junction inhibitor. The drug with optimal inhibitory activity, PQ1, was tested for inhibition and was found to inhibit dye transfer by 70% at 10 μM. Retinal …

Worldwide Variation In The Doubling Time Of Alzheimer's Disease Incidence Rates, Kathryn Ziegler-Graham, Ron Brookmeyer, Elizabeth Johnson, H. Michael Arrighi

Ron Brookmeyer

Background The doubling time is the number of chronological years for the age-specific incidence rate to double in magnitude. Doubling times describe the rate of increase of the risk of Alzheimer's disease (AD) with advancing age. Estimates of doubling times of AD assist in understanding disease etiology and forecasting future disease prevalence. The objective of this study was to investigate regional and gender differences in the doubling of AD age-specific incidence rates.

Methods We identified all studies in the peer review literature that reported age-specific incidence rates for AD. We modeled the logarithm of the incidence rate as a linear …

Simultaneous Confidence Bands For The Coefficient Function In Functional Regression, Philip T. Reiss

Philip T. Reiss

No abstract provided.

Reframing Global Health & Environmental Issues In The 21st Century, Nat Quansah

Nat Quansah

No abstract provided.

Inferring Group Differences In Brain Connectivity From Functional Magnetic Resonance Images, Philip T. Reiss

Philip T. Reiss

No abstract provided.

Reliability Of Functional Connectivity Networks: How Can We Assess It?, Philip T. Reiss

Philip T. Reiss

No abstract provided.

On Correcting The Overestimation Of The Permutation Based False Discovery Rate Estimator., Shuo Jiao, Shunpu Zhang

Shuo Jiao

Motivation: Recent attempts to account for multiple testing in the analysis of microarray data have focused on controlling the false discovery rate (FDR), which is defined as the expected percentage of the number of false positive genes among the claimed significant genes. As a consequence, the accuracy of the FDR estimators will

be important for correctly controlling FDR. Xie et al. found that the standard permutation method of estimating FDR is biased and proposed to delete the predicted differentially expressed (DE) genes in the estimation of FDR for one-sample comparison. However, we notice that the formula of the FDR used …

Is Reporting On Interventions A Weak Link In Understanding How And Why They Work? A Preliminary Exploration Using Community Heart Health Exemplars, Barbara Riley, Joanne Macdonald, Omaima Mansi, Anita Kothari, Donna Kurtz, Linda Vontettenborn, Nancy Edwards

Anita Kothari

Background: The persistent gap between research and practice compromises the impact of multi-level and multi-strategy community health interventions. Part of the problem is a limited understanding of how and why interventions produce change in population health outcomes. Systematic investigation of these intervention processes across studies requires sufficient reporting about interventions. Guided by a set of best processes related to the design, implementation, and evaluation of community health interventions, this article presents preliminary findings of intervention reporting in the published literature using community heart health exemplars as case examples.

Methods: The process to assess intervention reporting involved three steps: selection of …

Writing Research Proposal: Literature Review And Database Search, Mamoudou H. Dicko Prof.

Pr. Mamoudou H. DICKO, PhD

Bayesian Identification, Selection And Estimation Of Functions In High-Dimensional Additive Models, Anastasios Panagiotelis, Michael Smith

Michael Stanley Smith

In this paper we propose an approach to both estimate and select unknown smooth functions in an additive model with potentially many functions. Each function is written as a linear combination of basis terms, with coefficients regularized by a proper linearly constrained Gaussian prior. Given any potentially rank deficient prior precision matrix, we show how to derive linear constraints so that the corresponding effect is identified in the additive model. This allows for the use of a wide range of bases and precision matrices in priors for regularization. By introducing indicator variables, each constrained Gaussian prior is augmented with a …

Microproteomics: Analysis Of Protein Diversity In Small Samples, Howard B. Gutstein, Jeffrey S. Morris, Suresh P. Annangudi, Jonathan V. Sweedler

Jeffrey S. Morris

Proteomics, the large-scale study of protein expression in organisms, offers the potential to evaluate global changes in protein expression and their post-translational modifications that take place in response to normal or pathological stimuli. One challenge has been the requirement for substantial amounts of tissue in order to perform comprehensive proteomic characterization. In heterogeneous tissues, such as brain, this has limited the application of proteomic methodologies. Efforts to adapt standard methods of tissue sampling, protein extraction, arraying, and identification are reviewed, with an emphasis on those appropriate to smaller samples ranging in size from several microliters down to single cells. The …

Comment On Global Dynamics Of Biological Systems, Radhakrishnan Nagarajan

Radhakrishnan Nagarajan

No abstract provided.

The T-Mixture Model Approach For Detecting Differentially Expressed Genes In Microarrays, Shuo Jiao, Shunpu Zhang

Shuo Jiao

The finite mixture model approach has attracted much attention in analyzing microarray data due to its robustness to the excessive variability which is common in the microarray data. Pan (2003) proposed to use the normal mixture model method (MMM) to estimate the distribution of a test statistic and its null distribution. However, considering the fact that the test statistic is often of t-type, our studies find that the rejection region from MMM is often significantly larger than the correct rejection region, resulting an inflated type I error. This motivates us to propose the t-mixture model (TMM) approach. In this paper, …

Mapping As A Knowledge Translation Tool For Ontario Early Years Centres: Views From Data Analysts And Managers, Anita Kothari, S. Michelle Driedger, Julia Bickford, Jason Morrison, Michael Sawada, Ian D. Graham, Eric Crighton

Anita Kothari

Background: Local Ontario Early Years Centres (OEYCs) collect timely and relevant local data, but knowledge translation is needed for the data to be useful. Maps represent an ideal tool to interpret local data. While geographic information system (GIS) technology is available, it is less clear what users require from this technology for evidence-informed program planning. We highlight initial challenges and opportunities encountered in implementing a mapping innovation (software and managerial decision-support) as a knowledge translation strategy.

Methods: Using focus groups, individual interviews and interactive software development events, we taped and transcribed verbatim our interactions with nine OEYCs in Ontario, Canada. …

Software For Fitting Hierarchical Spatial Functional Models, Veera Baladandayuthapani

Veera Baladandayuthapani

No abstract provided.

Direct Effect Models, Mark J. Van Der Laan, Maya L. Petersen

Maya Petersen

The causal effect of a treatment on an outcome is generally mediated by several intermediate variables. Estimation of the component of the causal effect of a treatment that is not mediated by an intermediate variable (the direct effect of the treatment) is often relevant to mechanistic understanding and to the design of clinical and public health interventions. Robins, Greenland and Pearl develop counterfactual definitions for two types of direct effects, natural and controlled, and discuss assumptions, beyond those of sequential randomization, required for the identifiability of natural direct effects. Building on their earlier work and that of others, this article …

Characterizing Pharmacy And Medical Claims For A Private Insurance Polypharmacy Population, Brian W. Bresnahan, Kent M. Koprowicz, Sanchita Roy Choudhury, Louis P. Garrison, Ed Wong

Kent M Koprowicz

Objectives: To describe and characterize a group of private insurance members taking multiple medications over a one-year period. Methods: Persons were selected for this polypharmacy analysis if they had at least five unique maintenance prescriptions in their pharmacy claims records for the period of January-March 2005, based on a customized list of chronic medications. The full set of pharmacy and medical claims for these members were evaluated for a twelve month period, October 2004 to September 2005. Standard descriptive statistics were calculated to characterize the population. Logistic regression models were used to assess the association of pharmacy claims and “safety …

Multiple Testing Procedures Under Confounding, Debashis Ghosh

Debashis Ghosh

While multiple testing procedures have been the focus of much statistical research, an important facet of the problem is how to deal with possible confounding. Procedures have been developed by authors in genetics and statistics. In this chapter, we relate these proposals. We propose two new multiple testing approaches within this framework. The first combines sensitivity analysis methods with false discovery rate estimation procedures. The second involves construction of shrinkage estimators that utilize the mixture model for multiple testing. The procedures are illustrated with applications to a gene expression profiling experiment in prostate cancer.

Joint Variable Selection And Classification With Immunohistochemical Data, Debashis Ghosh, Ratna Chakrabarti

Debashis Ghosh

To determine if candidate cancer biomarkers have utility in a clinical setting, validation using immunohistochemical methods is typically done. Most analyses of such data have not incorporated the multivariate nature of the staining profiles. In this article, we consider modelling such data using recently developed ideas from the machine learning community. In particular, we consider the joint goals of feature selection and classification. We develop esti- mation procedures for the analysis of immunohistochemical profiles using the least absolute selection and shrinkage operator. These lead to novel and flexible models and algorithms for the analysis of compositional data. The techniques are …

An Improved Model Averaging Scheme For Logistic Regression, Debashis Ghosh, Zheng Yuan

Debashis Ghosh

Recently, penalized regression methods have attracted much attention in the statistical literature. In this article, we argue that such methods can be improved for the purposes of prediction by utilizing model averaging ideas. We propose a new algorithm that combines penalized regression with model averaging for improved prediction. We also discuss the issue of model selection versus model averaging and propose a diagnostic based on the notion of generalized degrees of freedom. The proposed methods are studied using both simulated and real data.

Measuring The Dynamic Surface Accessibility Of Rna With The Small Paramagnetic Molecule Tempol, Vincenzo Venditti, Neri Niccolai, Samuel E. Butcher

Vincenzo Venditti

The surface accessibility of macromolecules plays a key role in modulating molecular recognition events. RNA is a complex and dynamic molecule involved in many aspects of gene expression. However, there are few experimental methods available to measure the accessible surface of RNA. Here, we investigate the accessible surface of RNA using NMR and the small paramagnetic molecule TEMPOL. We investigated two RNAs with known structures, one that is extremely stable and one that is dynamic. For helical regions, the TEMPOL probing data correlate well with the predicted RNA surface, and the method is able to distinguish subtle variations in atom …

Important, But Odd And Obscure, Reasons To Use The Library, Maxine G. Schmidt

Maxine G Schmidt

No abstract provided.

Multinomial Logistic Regression: An Application To Estimating Performance Of A Multiple Screening Test For Bowel Cancer When Negatives Are Unverified., Chris Lloyd, Don Frommer

Chris J. Lloyd

This paper describes a method of estimating the performance of a multiple screening test where those who test negative do not have their true disease status determined. The methodology is motivated by a dataset on 49,927 subjects who were given K=6 binary tests for bowel cancer. A complicating factor is that individuals may have polyps present in the bowel, a condition that the screening test is not designed to detect but which may be worth diagnosing. The methodology is based on a multinomial logit model for Pr(S|R_6), the probability distribution of patient status S (healthy, polyps or diseased) conditional on …