Medicine and Health Sciences Commons^™

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 …

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 …

Antibacterial Activity Of Indium Curcumin And Indium Diacetylcurcumin, Keivan Zandi

Keivan Zandi

Studies on curcumin, the principal element of turmeric powder, have demonstrated several biological actions such as antibacterial activity. Evaluation of new analogs or new compounds of curcumin for their antibacterial effect is interesting for researchers. In this in vitro study, we attempted to test the antibacterial activity of indium curcumin (In(CUR)(3)), indium diacetylcurcumin (In(DAC)(3)), and diacetylcurcumin (DAC) in comparison with curcumin. The action of these agents were examined on Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 14990), Pseudomonas aeruginosa (ATCC 27853), and Escerichia coli (ATCC 25922). Curcumin was effective against S. aureus and S. epidermidis, whereas In(DAC)(3) showed activity against …

The Effects Of Lactation And Negative Energy Balance On Kisspeptin-Stimulated Luteinizing Hormone And Growth Hormone In Dairy Cows, Brian K. Whitlock, Joseph A. Daniel, Robyn R. Wilborn, Herris S. Maxwell, Barbara P. Steele, James L. Sartin

Brian K Whitlock, PhD, DVM, DACT

Kisspeptin, a neuroendocrine regulator of gonadotropin releasing hormone, is hypothesized to integrate nutrition and hormones critical to metabolism and the regulation of reproduction. Since the negative energy balance of early lactation is associated with reduced fertility via suppression of gonadotropin secretion and enhanced growth hormone (GH) responsiveness, this experiment was designed to determine the effects of stage of lactation and negative energy balance on kisspeptin-10 (Kp-10) stimulated luteinizing hormone (LH) and GH concentrations. Five nonlactating [5.1 ± 0.8 (SEM) years; 577 ± 19 kg body weight (BW)] and five lactating [4.1 ± 0.6 years; 608 ± 11 kg BW] multiparous …

Secondary Prevention For Acute Coronary Syndrome In Rural South Australia: Are Drugs Best? What About The Rest?, Tracey Wachtel, Angela Kucia, Jennene Greenhill

Angela Kucia

Acute coronary syndrome (ACS) is a major cause of morbidity and mortality worldwide. Current Australian clinical guidelines recommend all patients with ACS receive comprehensive secondary prevention services to address this burden. Optimal patient outcomes rely on the timely and effective implementation of proven therapies and for secondary prevention to be successful, pharmcological interventions must be combined with cardiovascular disease (CVD) risk factor identification and management. The ability to implement clinical guidelines is also reliant on available resources, yet many rural populations in Australia do not have access to structured secondary prevention services, and the level of support available to them …

A Case Of Cutaneous Larva Migrans Acquired From Soiled Toilet Floors In Urban Kuala Lumpur, Noorzurani Robson Associate Prof. Dr., S Othman

Associate Prof. Dr. Noorzurani Robson

Despite being a common skin dermatosis in the tropics, physicians in the tropics may miss the diagnosis of cutaneous larva migrans for other pruritic skin manifestation. This is especially in those who live in urban housing with no history of travel. Cutaneous larva migrans, an intensely pruritic skin pathology is mainly contracted by people with history of beach holiday or contact with moist soft sand which had been contaminated with dog or cat faeces. This article reports a patient who presented with intensely itchy papular spots over the dorsum of his foot after walking barefooted in an urban toilet soiled …

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 …

Intrinsic Severity As A Determinant Of Antiepileptic Drug Refractoriness, Michael A. Rogawski, Michael R. Johnson

Michael A. Rogawski

For the most part, resistance to medications in epilepsy is independent of the choice of antiepileptic drug. This simple clinical observation constrains the possible biological mechanisms for drug refractory epilepsy by imposing a requirement to explain resistance for a diverse set of chemical structures that act on an even more varied group of molecular targets. To date, research on antiepileptic drug refractoriness has been guided by the “drug transporter overexpression” and the “reduced drug-target sensitivity” hypotheses. These concepts posit that drug refractoriness is a condition separate from the underlying epilepsy. Inadequacies in both hypotheses mandate a fresh approach to the …

What Clinical Observations On The Epidemiology Of Antiepileptic Drug Intractability Tell Us About The Mechanisms Of Pharmacoresistance, Michael Rogawski

Michael A. Rogawski

In the past several years, there have been important advances in the clinical epidemiology of antiepileptic drug resistance, as reviewed by Mohanraj and Brodie. It would appear that by and large, intractability is independent of the choice of antiepileptic drug (AED). Many patients will become seizure free on the first agent tried, irrespective of which one their physician decides to pick. Nonresponders to the first drug are in a different category: it is likely that they will continue to have seizures no matter which medicine or combination of medicines is tried. This simple clinical observation puts important constraints on the …

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 …

Gene Alterations By Peroxisome Proliferator-Activated Receptor Gamma Agonists In Human Colorectal Cancer Cells, Maria Cekanova, J Yuan, X Li, K B. Kim, Seung J. Baek

Maria Cekanova MS, RNDr, PhD

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear transcription factor that controls the genes involved in metabolism and carcinogenesis. In the present study, we examined the alteration of gene expression in HCT-116 human colorectal cancer cells by PPARgamma agonists: MCC-555 (5 microM), rosiglitazone (5 microM), and 15-deoxy-Delta12,14-prostaglandin J2 (1 microM). The long-oligo microarray data revealed a list of target genes commonly induced (307 genes) and repressed (32 genes) by tested PPARgamma agonists. These genes were analyzed by Onto-Express software and KEGG pathway analysis and revealed that PPARgamma agonists are involved in cell proliferation, focal adhesion, and several signaling pathways. …

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.

Continuous St/T Wave Monitoring During An Acute Coronary Syndrome Presentation In Patients With The Coronary Slow Flow Phenomenon (Csfp), Natalie Cutri, Angela Kucia, John F. Beltrame

Angela Kucia

The coronary slow flow phenomenon (CSFP) is a coronary microvascular disorder that typically presents as an acute coronary syndrome and is characterised by delayed vessel opification on angiography in the absence of obstructive coronary artery disease. This study compared the frequency of the ST segment (STs) and T wave (TW) change during continuous ST/T wave monitoring in healthy controls and patients with the CSFP.

The Effects Of Positional Changes On T Wave Amplitude In Healthy Subjects, Natalie Cutri, John F. Beltrame, Angela M. Kucia

Angela Kucia

ST segment (STs) and T wave (Tw) changes are markers of myocardial ischaemia. However, STs changes have been reported with changes in body position. The effect of body position on Tw changes is unknown and the objective of this study.

Software For Fitting Hierarchical Spatial Functional Models, Veera Baladandayuthapani

Veera Baladandayuthapani

No abstract provided.

Sera Of Iga Nephropathy Patients Contain A Heterogeneous Population Of Relatively Cationic Alpha-Heavy Chains, Onn Haji Hashim

Onn Haji Hashim

Sera of IgA nephropathy (IgAN) patients and normal subjects were analysed by two-dimensional (2-D) gel electrophoresis. Densitometric analysis of the 2-D gels of IgAN patients and normal subjects revealed that their protein maps were comparable. There was no shift of pI values in the major alpha-heavy chain spots. However, the volume of the alpha-heavy chain bands were differently distributed. Distribution was significantly lower at the anionic region in IgAN patients (mean anionic:cationic ratio of 1.184 +/- 0.311) as compared to normal healthy controls (mean anionic:cationic ratio of 2.139 +/- 0.538). Our data are in support of the previously reported findings …

Effect Of Traditional Starter Inoculation Rate On Sorghum Beer Quality, Theodore N'Dede Djeni

Theodore N'Dede Djeni

In the way to determine, the effect of inoculation rate of traditional starter on sorghum beer quality, fermentations were initiated with different inoculation rates [0% (control), 0.5, 1, 1.5 and 2% (w vG1)] at 35°C. Then fermentation parameters such as utilization of sugars and production of CO , alcohol, organic acids and 2 yeast biomass were assayed during the process. At the beginning of the fermentation, sugar consumption rate increased with inoculation rate. But from 8 h of fermentation, all inoculated systems shown similar consumption rate and led to beers with the same sugar content. The lag phase in CO …

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.

Brivaracetam: A Rational Drug Discovery Success Story, Michael Rogawski

Michael A. Rogawski

Levetiracetam, the alpha-ethyl analogue of the nootropic piracetam, is a widely used antiepileptic drug (AED) that provides protection against partial seizures and is also effective in the treatment of primary generalized seizure syndromes including juvenile myoclonic epilepsy. Levetiracetam was discovered in 1992 through screening in audiogenic seizure susceptible mice and, 3 years later, was reported to exhibit saturable, stereospecific binding in brain to a approximately 90 kDa protein, later identified as the ubiquitous synaptic vesicle glycoprotein SV2A. A large-scale screening effort to optimize binding affinity identified the 4-n-propyl analogue, brivaracetam, as having greater potency and a broadened spectrum of activity …

New Molecular Targets For Antiepileptic Drugs: Alpha2delta, Sv2a, And Kv7/Kcnq/M Potassium Channels, Michael A. Rogawski, Carl W. Bazil

Michael A. Rogawski

Many currently prescribed antiepileptic drugs (AEDs) act via voltage-gated sodium channels, through effects on gamma-aminobutyric acid-mediated inhibition, or via voltage-gated calcium channels. Some newer AEDs do not act via these traditional mechanisms. The molecular targets for several of these nontraditional AEDs have been defined using cellular electrophysiology and molecular approaches. Here, we describe three of these targets: alpha(2)delta, auxiliary subunits of voltage-gated calcium channels through which the gabapentinoids gabapentin and pregabalin exert their anticonvulsant and analgesic actions; SV2A, a ubiquitous synaptic vesicle glycoprotein that may prepare vesicles for fusion and serves as the target for levetiracetam and its analog brivaracetam …

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

Maxine G Schmidt

No abstract provided.