Using duplicate genotyped data in genetic analyses: testing association and estimating error rates.

Although researchers use duplicate genotyped data to calculate an inconsistency rate, there is no power analysis to assess the value of the duplicate data. In this paper, we present a model in which the genotyping error rate is related to the inconsistency rate. We extend the g genotype by h phenotype chi-squared test to incorporate the duplicate genotyped data.

Radiation-induced leukemia: lessons from history.

Beginning in 1895, with the discovery of x-rays, alpha and beta radiation, uranium, radium, thorium, and polonium, the fascinating story of the beginning of knowledge concerning the existence of ionizing radiation unfolds. This brief history of radiation and leukemia is divided into two main parts: the first 50 years, which deals with the confusion regarding radiation effects and the failure to clearly recognize that exposure to ionizing radiation may induce leukemia. The second part focuses on the last 60 years, when the radiation induction of leukemia was accepted and some progress achieved in understanding the clinical and pathophysiological characteristics of radiation-induced leukemia.

Remission and relapse after the first hospital admission in psychotic depression: a 4-year naturalistic follow-up.

Background: Few studies have examined the course of illness among severely depressed patients ascertained at first hospitalization. Using data from the Suffolk County Mental Health Project (SCMHP), we investigated the times to and predictors of the first full remission and the first relapse during a 4-year period in a first-admission cohort with major depressive disorder (MDD) with psychotic features.

Method: The cohort included 87 county-wide, first-admission patients with a longitudinal consensus diagnosis of MDD with psychotic features who were systematically followed over a 4-year period.

The impact of genotype misclassification errors on the power to detect a gene-environment interaction using cox proportional hazards modeling.

This paper extends gene-environment (G x E) interaction study designs in which the gene (G) is known and the environmental variable (E) is specified to the analysis of 'time-to-event' data, using Cox proportional hazards (PH) modeling. The objectives are to assess whether a random sample of subjects can be used to detect a specific G x E interaction and to study the sensitivity of the power of PH modeling to genotype misclassification. We find that a random sample of 2,100 is sufficient to detect a moderate G x E interaction.

Determinants of parental discipline practices: a national sample from primary care practices.

National guidelines urge pediatricians to address discipline as part of anticipatory guidance, yet pediatricians know little about what leads parents to use different discipline approaches. Parents seen in Pediatric Research in Office Settings practices participated in an office-based survey before the well-child visit for children 2 to 11 years old (N = 2134). Parents reported using the following discipline approaches frequently: time-outs (42%), removal of privileges (41%), sent to bedroom (27%), yelling (13%), and spanking (9%).

Smoking involvement during adolescence among African Americans and Puerto Ricans: risks to psychological and physical well-being in young adulthood.

The major aim of this study was to examine the longitudinal association between adolescent smoking involvement and self-reported psychological and physical outcomes in young adulthood. Participants included 333 African Americans and 329 Puerto Ricans who were surveyed in 1990 in their New York City schools and interviewed in 1995 and 2000-2001, primarily in their homes. The psychological outcomes included ego integration, symptoms of depression, anxiety, and interpersonal difficulty.

Cardioversion of persistent atrial arrhythmia after treatment with venlafaxine in successful management of major depression and posttraumatic stress disorder.

There is increasing evidence linking depression and cardiovascular disease. However, the authors could find no literature directly linking depression with atrial fibrillation or atrial flutter. The authors report the case of a patient with uncontrolled atrial arrhythmia who cardioverted to normal sinus rhythm after treatment of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) with venlafaxine.

The effects of SNP genotyping errors on the power of the Cochran-Armitage linear trend test for case/control association studies.

The questions addressed in this paper are: What single nucleotide polymorphism (SNP) genotyping errors are most costly, in terms of minimum sample size necessary (MSSN) to maintain constant asymptotic power and significance level, when performing case-control studies of genetic association applying the Cochran-Armitage trend test? And which trend test or chi2 test is more powerful under standard genetic models with genotyping errors? Our strategy is to expand the non-centrality parameter of the asymptotic distribution of the trend test to approximate the MSSN using a Taylor series linear in the genotyping error rates. We apply our strategy to example scenarios that assume recessive, dominant, additive, or over-dominant disease models. The most costly errors are recording the more common homozygote as the less common homozygote, and the more common homozygote as the heterozygote, with MSSN that become indefinitely large as the minor SNP allele frequency approaches zero.

[The religious orthodox family in the pediatric hemato-oncology department].

Background: Extensive research has been conducted on the subject of cultural influences on behaviors, attitudes, beliefs and interpersonal relations of patients in the medical world. Cancer is a life-threatening illness and the intense emotional reactions to it enhance the influence of subcultural behaviors and attitudes towards the illness, the treatments and towards the medical staff.

Aims: This paper aims to describe what happens at the encounter between the medical subculture, which is mainly secular, and the orthodox subculture, of the child treated for cancer and his family.

The relationship of personality and behavioral development from adolescence to young adulthood and subsequent parenting behavior.

The purpose of the study was to examine the association of parental personality, behavior, and substance use during adolescence and adulthood as related to the later parent-offspring relationship. The sample consisted of 297 parents (M age 32 yr.), who were first interviewed at earlier points in their lives in childhood and early adolescence at six points in time, extending from 1983 to 2002.

Clinician practice patterns: linking to community resources for childhood aggression.

Creating links to community resources for childhood aggression is one component of office-based violence prevention. Evidence is lacking regarding the effect of training clinicians to make these referrals and families' responses to them. Clinicians who received training (n=47) and parents (1093) were queried on the provision of referrals immediately after the visit.

Evidence for increased atrial sympathetic innervation in persistent human atrial fibrillation.

Objective: In this study, we aimed to compare the level of atrial sympathetic innervation in human atrial fibrillation (AF) to that in sinus rhythm (SR).

Background: Histological studies of atrial tissue obtained from animals with experimentally induced AF indicate that sympathetic hyperinnervation could play a role in the pathogenesis of AF.

Methods: In 24 patients (12 in SR and 12 in AF) undergoing bypass surgery, we collected right atrial appendage tissue.

Increase in linkage information by stratification of pedigree data into gold-standard and standard diagnoses: application to the NIMH Alzheimer Disease Genetics Initiative Dataset.

Patients diagnosed with a standard clinical method (subject to misclassification error) are often combined with patients diagnosed with a gold-standard method (with zero or very small misclassification error) in family-based studies of complex disease. For example, non-autopsied patients (NAP) are often included along with autopsy-proven (AP) patients in family-based studies of complex diseases, such as Alzheimer's disease (AD). Theoretical and simulation studies suggest that certain misclassification errors can result in severe reduction of power in genetic linkage and association analyses and that phenotype (or diagnostic) error can produce misleading results.

Computing asymptotic power and sample size for case-control genetic association studies in the presence of phenotype and/or genotype misclassification errors.

It is well established that phenotype and genotype misclassification errors reduce the power to detect genetic association. Resampling a subset of the data (e.g, double-sampling) of genotype and/or phenotype with a gold standard measurement is one method to address this issue.

Increasing power for tests of genetic association in the presence of phenotype and/or genotype error by use of double-sampling.

Phenotype and/or genotype misclassification can: significantly increase type II error probabilities for genetic case/control association, causing decrease in statistical power; and produce inaccurate estimates of population frequency parameters. We present a method, the likelihood ratio test allowing for errors (LRTae) that incorporates double-sample information for phenotypes and/or genotypes on a sub-sample of cases/controls. Population frequency parameters and misclassification probabilities are determined using a double-sample procedure as implemented in the Expectation-Maximization (EM) method.

Parental media mediation styles for children aged 2 to 11 years.

Background: Studies indicate that children use media (television, video, and computer) more than the recommended limit of 2 h/d, but little is known about parents' role in mediating their children's media use.

Design: Office-based survey. Data were collected on demographics, reported media behaviors, parental awareness about media effects, television in the bedroom, and parental concern.

Does clinical presentation explain practice variability in the treatment of febrile infants?

Background: Previous studies documented considerable variability in the treatment of febrile infants, despite the existence of practice guidelines for this condition. None of those studies documented the extent to which this variability is accounted for by differences in clinical severity.

Objective: To quantify the individual effects of the patient's clinical presentation, demographic, provider, and practice characteristics, and regional variables on practice variability in the evaluation and treatment of febrile infants.

Proteolytic surface functionalization enhances in vitro magnetic nanoparticle mobility through extracellular matrix.

Steric barriers such as collagen I sharply limit interstitial delivery of macromolecular and nanoparticle (NP) based therapeutic agents. Collagenase-linked superparamagnetic NPs overcame these barriers and moved through in vitro extracellular matrix (ECM) at 90 microm h(-1), a rate similar to invasive cells, under the influence of a magnetic field. NP migration in ECM diminished linearly over 5 days.

Using mixture models to characterize disease-related traits.

We consider 12 event-related potentials and one electroencephalogram measure as disease-related traits to compare alcohol-dependent individuals (cases) to unaffected individuals (controls). We use two approaches: 1) two-way analysis of variance (with sex and alcohol dependency as the factors), and 2) likelihood ratio tests comparing sex adjusted values of cases to controls assuming that within each group the trait has a 2 (or 3) component normal mixture distribution. In the second approach, we test the null hypothesis that the parameters of the mixtures are equal for the cases and controls.

A gene-model-free method for linkage analysis of a disease-related-trait based on analysis of proband/sibling pairs.

In this paper we investigate the power of finding linkage to a disease locus through analysis of the disease-related traits. We propose two family-based gene-model-free linkage statistics. Both involve considering the distribution of the number of alleles identical by descent with the proband and comparing siblings with the disease-related trait to those without the disease-related-trait.

Characteristics of replicated single-nucleotide polymorphism genotypes from COGA: Affymetrix and Center for Inherited Disease Research.

Genetic Analysis Workshop 14 provided re-genotyped single-nucleotide polymorphism (SNP) data. Specifically, both Center for Inherited Disease Research (CIDR) and Affymetrix genotyped the same 11,560 SNPs from the Affymetrix GeneChip Mapping 10K Array marker set on the same 184 individuals from the Collaborative Study on the Genetics of Alcoholism database. While the inconsistency rate between CIDR and Affymetrix (two different genotypes for the same subject) was low (0.

Administrative restructuring of a residency training program for improved efficiency and output.

Objectives: Canadian residency training programs (RTP) have a program director (PD) and a residency program committee (RPC) overseeing program administration. Limited guidance is available about the ideal administrative structure of an RTP. This article describes administrative load in Canadian RTPs, presents a novel approach to delegating core administrative tasks within the RTP, and provides initial impressions of positive outcomes following implementation of this new system.

Anticipatory guidance topics: are more better?

Objective: Anticipatory guidance is a cornerstone of primary care pediatrics. Despite the fact that retention of information is essential for later action, data are lacking on what parents recall immediately after the visit and 1 month later and how the total number of topics discussed affects this outcome.

Methods: Parents and practitioners completed postvisit surveys of anticipatory guidance topics discussed during health-maintenance visits for children ages 2-11.

Choice of urine collection methods for the diagnosis of urinary tract infection in young, febrile infants.

Background: The optimal method of urine collection in febrile infants is debatable; catheterization, considered more accurate, is technically difficult and invasive.

Objectives: To determine predictors of urethral catheterization in febrile infants and to compare bag and catheterized urine test performance characteristics.

Design: Prospective analysis of infants enrolled in the Pediatric Research in Office Settings' Febrile Infant Study.

PAWE-3D: visualizing power for association with error in case-control genetic studies of complex traits.

Unlabelled: A website that plots power and sample size calculations over a range of up to eight parameters (including diagnostic misclassification error parameters) for two commonly used statistical tests of genetic association, the linear trend test and the genotypic test of association.

Availability: This method is made available via the website http://linkage.rockefeller.