Medicine and Health Sciences Commons^™

Exact One-Sided Confidence Limits For The Difference Between Two Correlated Proportions, Chris Lloyd, Max V. Moldovan

Chris J. Lloyd

We construct exact and optimal one-sided upper and lower confidence bounds for the difference between two probabilities based on matched binary pairs using well-established optimality theory of Buehler (1957). Starting with five different approximate loer and upper limits, we adjust them to have coverage probability exactly equal to the desired nominal level and then compare the resulting exact limits by their mean size. Exact limits based on the signed root likelihood ratio statistic are preferred and recommended for practical use.

A Role For The Forebrain In Mediating Time-Of-Day Differences In Glucocorticoid Counterregulatory Responses To Hypoglycemia In Rats, Lori M. Gorton, Arshad M. Khan, Maryann Bohland, Graciela Sanchez-Watts, Casey M. Donovan, Alan G. Watts

Arshad M. Khan, Ph.D.

No abstract provided.

Functional Principal Component Regression And Functional Partial Least Squares, Philip T. Reiss, R. Todd Ogden

Philip T. Reiss

Regression of a scalar response on signal predictors, such as near-infrared (NIR) spectra of chemical samples, presents a major challenge when, as is typically the case, the dimension of the signals far exceeds their number. Most solutions to this problem reduce the dimension of the predictors either by regressing on components--e.g. principal component regression (PCR) and partial least squares (PLS)--or by smoothing methods which restrict the coefficient function to the span of a spline basis. This paper introduces functional versions of PCR and PLS, which combine both of the above dimension reduction approaches. Two versions of functional PCR are developed, …

Meta-Analysis Evidence Of A Differential Risk Of The Fcrl3 -169t->C Polymorphism In White And East Asian Rheumatoid Arthritis Patients, Steven J. Schrodi, Begovich Ann, Chang Monica

Steven J Schrodi

Association between a functional promoter polymorphism (rs7528684) in the Fc receptor-like gene, FCRL3, and rheumatoid arthritis (RA) has been observed in 3 independent Japanese case-control sample sets ([1][2]). Studies examining the role of this polymorphism in risk of RA in 9 independent white sample sets, however, have yielded conflicting results ([3-8]). Further, a large study of Korean subjects failed to demonstrate association of this single-nucleotide polymorphism (SNP) with RA ([9]). Although the precise function of FCRL3, which has strong structural homology with the classic Fc receptors, is unknown, the existing data are consistent with the hypothesis that it may influence …

Catecholaminergic Control Of Mitogen-Activated Protein Kinase Signaling In Paraventricular Neuroendocrine Neurons In Vivo And In Vitro: A Proposed Role During Glycemic Challenges, Arshad M. Khan, Todd A. Ponzio, Graciela Sanchez-Watts, B. Glenn Stanley, Glenn I. Hatton, Alan G. Watts

Arshad M. Khan, Ph.D.

No abstract provided.

Organisms Associated With Bacterial Vaginosis In Nigerian Women As Determined By Pcr-Dgge And 16s Rrna Gene Sequence, Kingsley Anukam, Gregor Reid

Kingsley C Anukam

Background: Bacterial vaginosis (BV) is a condition with diverse etiology. This condition predisposes women to increased susceptibility to sexually transmitted diseases, including human immunodeficiency virus (HIV) infections and preterm birth. The diagnostic methods currently adopted in the evaluation of patient samples for BV are arguably Amsel criteria, and Nugent score that require microscopy and expert interpretation. These two methods are still subjective. Objective: The objective of this study was to determine the organisms present in the vagina of 34 HIV negative Nigerian women diagnosed as having bacterial vaginosis by using molecular techniques. Methods: The vaginal samples were subjected to DNA …

A Large-Scale Rheumatoid Arthritis Genetic Study Identifies Association At Chr 9q33.2, Steven J. Schrodi

Steven J Schrodi

No abstract provided.

The Neuropharmacology Of The Ketogenic Diet, Adam Hartman, Maciej Gasior, Elaine Vining, Michael Rogawski

Michael A. Rogawski

The ketogenic diet is a valuable therapeutic approach for epilepsy, one in which most clinical experience has been with children. Although the mechanism by which the diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in brain. The pattern of protection of the ketogenic diet in animal models of seizures is distinct from that of other anticonvulsants, suggesting that it has a unique mechanism of action. During consumption of the ketogenic diet, marked alterations in brain energy metabolism occur, with ketone …

High-Dose Pralidoxime For Organophosphorus Poisoning, Ashish Goel, Praveen Aggarwal, Sanjeev Bhoi, Vineet Gupta

Vineet Gupta, MD, FACP

No abstract provided.

Input Vs. Output Level Coupling Demonstrates Asymmetrical Attentional Biases, Gavin Buckingham, David Carey

Gavin Buckingham

The current study examined the performance of each limb as it reached across the body (the hard task), while yoked to it’s ipsilateral reaching counterpart (the easy task).

Epilepsy: Mechanisms Of Drug Action And Clinical Treatment, William Theodore, Michael Rogawski

Michael A. Rogawski

No abstract provided.

Modulation Of Ischaemic Contracture In Mouse Hearts: A 'Supraphysiological' Response To Adenosine, Melissa Reichelt, Laura Willems, Jason Peart, Kevin Ashton, G Matherne, Michael Blackburn, John Headrick

Kevin Ashton

While inhibition of ischaemic contracture was one of the first documented cardioprotective actions of exogenously applied adenosine, it is not known whether this is a normal function of endogenous adenosine generated during ischaemic stress. Additionally, the relevance of delayed contracture to postischaemic outcome is unclear. We tested the ability of endogenous versus exogenous adenosine to modify contracture (and postischaemic outcomes) in C57/Bl6 mouse hearts. During ischaemia, untreated hearts developed peak contracture (PC) of 85 ± 5 mmHg at 8.9 ± 0.8 min, with time to reach 20 mmHg (time to onset of contracture; TOC) of 4.4 ± 0.3 min. Adenosine …

Asymmetries In Attention Toward The Dominant Hand: Input Or Output?, Gavin Buckingham, Julie Main, David Carey

Gavin Buckingham

Peters (1981) suggested that an asymmetrical bias in attention (toward the right hand of right handers) could account for many manual asymmetries in bimanual task performance. Support for this notion comes from Honda (1982), who demonstrated preferential monitoring of the dominant hand during a bimanual reaching task, while Buckingham and Carey (2007) observed shorter refractory periods (dwell time in a bimanual discontinuous double-step reaching task) for the right hand.

Recent evidence may indicate an intentional (i.e. selection related behaviour – motor attention) bias toward the dominant hand (Bestelmeyer & Carey, 2004). The current study tests the hypothesis that the right …

Software To Forecast The Global Burden Of Alzheimer's Disease, Ron Brookmeyer, Elizabeth Johnson, Kathryn Ziegler-Graham, H. Michael Arrighi

Ron Brookmeyer

Software was developed to forecast the global burden of Alzheimer’s disease and evaluate the potential impact of interventions that delay disease onset and progression. The output includes 50 year projections of Alzheimer's disease prevalence by stage of disease and region of the world. The methods are based on a stochastic multi-state model The software incorporates U.N. worldwide population forecasts and data from epidemiological studies on risks of Alzheimer’s disease. The user can also supply their own population projections, and modify input parameters for the model including the disease incidence rates, effects of interventions on disease onset and progression, and stages …

The Anticonvulsant Activity Of Acetone, The Major Ketone Body In The Ketogenic Diet, Is Not Dependent On Its Metabolites Acetol, 1,2-Propanediol, Methylglyoxal, Or Pyruvic Acid, Maciej Gasior, Amy French, Michelle Joy, Rebecca Tang, Adam Hartman, Michael Rogawski

Michael A. Rogawski

BACKGROUND: Acetone, one of the principal ketone bodies elevated during treatment with the ketogenic diet, exhibits anticonvulsant properties that may contribute to the seizure protection conferred by the diet. The anticonvulsant mechanism of acetone is unknown, but it is metabolized to several bioactive substances that could play a role. METHODS: Acetone and its major metabolites-acetol, 1,2-propanediol, methylglyoxal, and pyruvic acid-were assessed for anticonvulsant activity in two mouse seizure models. Various doses of the substances administered intraperitoneally were characterized for their ability to elevate the threshold for clonic seizures induced by intravenous infusion of pentylenetetrazol (PTZ) and for protection against tonic …

Confidence Intervals For Biomarker-Based Human Immunodeficiecny Virus Incidence Estimates And Differences Using Prevalent Data, Ron Brookmeyer, S Cole, H Chu

Ron Brookmeyer

Prevalent biological specimens can be used to estimate human immunodeficiency virus (HIV) incidence using a two-stage immunologic testing algorithm that hinges on the average time, say T, between testing HIV positive on highly and less sensitive enzyme immunoassays. Common approaches to confidence interval (CI) estimation for this incidence measure have included (1) ignoring the random error in T or (2) employing a Bonferroni adjustment to the box method. The authors present alternative Monte Carlo-based CIs for this incidence measure, as well as CIs for the biomarker-based incidence difference; standard approaches to CIs are typically appropriate for the incidence ratio. Using …

Quantitative (Real-Time) Rt-Pcr In Cardiovascular Research, Kevin Ashton, John Headrick

Kevin Ashton

Quantitative (real-time) PCR (qPCR) represents a highly sensitive, sequence-specific, and reproducible technique for the gel-free detection and quantitation of nucleic acids. Owing to its large dynamic range and throughput, this approach has become the chosen method for rapid quantification of mRNA levels in biological samples. The sensitivity of this method permits the reliable detection of low concentrations of initial template, while delivering a linear range of up to 10 orders of magnitude in copy number. This chapter details the basic methodology behind key components of a qPCR experiment, including sample preparation, fluorescent chemistries, primer/probe design, and data analysis applicable to …

Attentional Vs. Intentional Biases In Hand Movements; Hand-Specific Coupling & Bimanual Reaching, Gavin Buckingham, David Carey

Gavin Buckingham

Most of the population is dextral, showing a clear preference for performing the vast majority of tasks with their right hand. Peters (1981) suggested that an asymmetrical bias in attention (toward the right hand in right handers) could account for many manual asymmetries in bimanual task performance, with the left hand unable to perform the attentionally demanding portion of the task. Likewise, Honda (1982) demonstrated preferential monitoring of the dominant hand during a bimanual reaching task. Recent evidence has also shown an intentional (i.e. output related motor attention) bias toward the dominant hand (Bestelmeyer & Carey, 2004), another possible factor …

Molecular Targets For Antiepileptic Drug Development, Brian S. Meldrum, Michael A. Rogawski

Michael A. Rogawski

This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the alpha subunits of voltage-gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently, alpha2-delta voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na+ …

Modeling The Effect Of Alzheimer's Disease On Mortality, Elizabeth Johnson, Ron Brookmeyer, Kathryn Ziegler-Graham

Ron Brookmeyer

Mortality rate ratios and the associated proportional hazards models have been used to summarize the effect of Alzheimer's disease on longevity. However, the mortality rate ratios vary by age and therefore do not provide a simple parsimonious summary of the effect of the disease on lifespan. Instead, we propose a new parameter that is defined by an additive multistate model. The proposed multistate model accounts for different stages of disease progression. The underlying assumption of the model is that the effect of disease on mortality is to add a constant amount to death rates once the disease progresses from an …

Single Unit And Population Responses During Inhibitory Gating Of Striatal Activity In Freely Moving Rats, Howard C. Cromwell

Howard Casey Cromwell

Abstract—The striatum is thought to be an essential region for integrating diverse information in the brain. Rapid inhibitory gating (IG) of sensory input is most likely an early factor necessary for appropriate integration to be completed. Gating is currently evaluated in clinical settings and is dramatically altered in a variety of psychiatric illnesses. Basic neuroscience research using animals has revealed specific neural sites involved in IG including the hippocampus, thalamus, brainstem, amygdala and medial prefrontal cortex. The present study investigated local IG in the basal ganglia structure of the striatum using chronic recording microwires. We obtained both single unit activations …

A Practical Illustration Of The Importance Of Realistic Individualized Treatment Rules In Causal Inference, Oliver Bembom, Mark J. Van Der Laan

Oliver Bembom

The effect of vigorous physical activity on mortality in the elderly is difficult to estimate using conventional approaches to causal inference that define this effect by comparing the mortality risks corresponding to hypothetical scenarios in which all subjects in the target population engage in a given level of vigorous physical activity. A causal effect defined on the basis of such a static treatment intervention can only be identified from observed data if all subjects in the target population have a positive probability of selecting each of the candidate treatment options, an assumption that is highly unrealistic in this case since …