Using the EM algorithm for Bayesian variable selection in logistic regression models with related covariates.

We develop a Bayesian variable selection method for logistic regression models that can simultaneously accommodate qualitative covariates and interaction terms under various heredity constraints. We use expectation-maximization variable selection (EMVS) with a deterministic annealing variant as the platform for our method, due to its proven flexibility and efficiency. We propose a variance adjustment of the priors for the coefficients of qualitative covariates, which controls false-positive rates, and a flexible parameterization for interaction terms, which accommodates user-specified heredity constraints. This method can handle all pairwise interaction terms as well as a subset of specific interactions. Using simulation, we show that this method selects associated covariates better than the grouped LASSO and the LASSO with heredity constraints in various exploratory research scenarios encountered in epidemiological studies. We apply our method to identify genetic and non-genetic risk factors associated with smoking experimentation in a cohort of Mexican-heritage adolescents.

Using Ascertainment for Targeted Resequencing to Increase Power to Identify Causal Variants.

Researchers continue to use genome-wide association studies (GWAS) to find the genetic markers associated with disease. Recent studies have added to the typical two-stage analysis a third stage that uses targeted resequencing on a randomly selected subset of the cases to detect the causal single-nucleotide polymorphism (SNP). We propose a design for targeted resequencing that increases the power to detect the causal variant. The design features an ascertainment scheme wherein only those cases with the presence of a risk allele are selected for targeted resequencing. We simulated a disease with a single causal SNP to evaluate our method versus a targeted resequencing design using randomly selected individuals. The simulation studies showed that ascertaining individuals for the targeted resequencing can substantially increase the power to detect a causal SNP, without increasing the false-positive rate.

The role of patients in the implementation of the National Kidney Foundation-Dialysis Outcomes Quality Initiative.

Patients have a fundamental right to be involved in making decisions that affect their health care treatment and outcomes. Patients need to be knowledgeable about disease process and treatment options to exercise this right. The National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Practice Guidelines on Hemodialysis Adequacy, Peritoneal Dialysis Adequacy, Treatment of Anemia of Chronic Renal Failure, and Vascular Access, introduced in 1997, include new clinical recommendations that may impact patient treatment choices. Access to these guidelines presents a unique professional opportunity to empower patients through education related to NKF-DOQI. This article highlights the role of patients in implementing NKF-DOQI in light of studies conducted by two renal patient organizations, the National Kidney Foundation (NKF) and the American Association of Kidney Patients (AAKP). Results from the AAKP survey indicate that end-stage renal disease patients are willing to change behavior to feel better and live longer. Results from the NKF focus study show that dialysis patients need to receive information about NKF-DOQI and understand its direct impact on patient outcomes. In addition, results from both studies reveal that patients feel strongly about participating in health care decisions that impact on their treatment and outcomes.

Continuous renal replacement therapy. A national perspective AACN/NKF.

Health care providers rely on quality continuing education programs to increase their knowledge and to acquire new skills. Participation in programs such as CVVH: Implications for Clinical Practice-the Patient, the Circuit, the Team can potentially improve patient outcomes. While this study identifies critical care nurses as a receptive professional group for further CRRT training, it also indicates that additional education in this topic may benefit other members of the critical care team as well. Therefore, because the critical care nurse's role, while crucial to the clinical management of patients undergoing CRRT, does not include prescribing or initiating CRRT therapy, it is difficult to predict the impact of future workshops on the increased and sustained use of CRRT in critical care arenas. If you would like additional information on CVVH: Implications for Practice-the Patient, the Circuit, the Team, please contact the National Kidney Foundation at (800) 622-9010, or the American Association of Critical Care Nurses at (800) 899-2226.

Adolescent egocentrism and cognitive functioning during late adolescence.

The relationship between adolescent egocentrism and post-formal thinking was examined in 163 college undergraduates. Participants were administered the Imaginary Audience Scale and the Social Paradigm Belief Inventory. Results showed that females had higher levels of adolescent egocentrism than did males. A weak negative correlation between egocentrism and cognitive reasoning was found for females during late adolescence. The findings are consistent with Peterson and Roscoe's (1991) study of egocentrism in older adolescent females.

Elimination of plasmid pMG110 from Escherichia coli by novobiocin and other inhibitors of DNA gyrase.

The ability of novobiocin to eliminate (cure) the wild-type plasmid pMG110 from Escherichia coli has been compared with that of other inhibitors of the gyrase B subunit and of the gyrase A subunit. Novobiocin eliminated pMG110 , producing over 99% plasmid loss at concentrations two- to eightfold below the MIC for bacterial growth. Structurally related compounds ( clorobiocin , coumermycin A1, isobutyryl novenamine , and decarbamyl novobiocin) varied in their ability to eliminate pMG110 . Higher concentrations of drugs were required to eliminate pMG110 from a gyrB( Cour ) strain, implicating DNA gyrase in the curing phenomenon. For these drugs, the ratio of the concentration effecting maximal plasmid elimination to the MIC varied from 0.16 to 1.1, indicating that curing cannot be explained simply by inhibition of a pool of DNA gyrase equally available for replication of the bacterial chromosome and the plasmid DNA molecule. Inhibitors of the gyrase A subunit, nalidixic acid and oxolinic acid, eliminated pMG110 only to variable low levels. The differences in the ability of the gyrase A and B subunit antagonists to eliminate plasmids are discussed.

Novobiocin-induced elimination of F'lac and mini-F plasmids from Escherichia coli.

Novobiocin eliminated (cured) F'lac and three low-copy-number mini-F plasmids (pML31, pMF21, and pMF45) from Escherichia coli to different extents. F'lac was cured 0 to 3%. pML31, whose replication region is contained on the 9-kilobase f5 EcoRI restriction enzyme fragment of F, was eliminated 10 to 92%. pMF21, deleted of the origin of mini-F replication at 42.6 kilobases on the F map and known to initiate from an origin at 45.1 kilobases, and its closely related derivative pMF45 were cured to the greatest extent (greater than 97%). pMF45 was eliminated from a wild-type bacterial strain but not from an isogenic novobiocin-resistant gyrB mutant strain, indicating involvement of the B subunit of DNA gyrase in the curing phenomenon. The number of bacteria containing pMF45 halved with each generation of growth in the presence of novobiocin, as is predicted for complete inhibition of plasmid DNA replication.

Rapid method for screening large numbers of Escherichia coli colonies for production of plasmid-mediated beta-lactamases.

A rapid, simple assay for screening large numbers of Escherichia coli colonies for production of certain plasmid-mediated beta-lactamases (including TEM-1, TEM-2, HMS-1, SHV-1, OXA-1, PSE-1, PSE-4, and CEP-2) is described. The technique, a modification of the method of Slack et al. for detection of beta-lactamase in limited numbers of Haemophilus influenzae clinical isolates (Lancet ii:906, 1977), uses filter paper impregnated with benzylpenicillin and a pH indicator dye (bromocresol purple) that changes color in the presence of beta-lactamase activity. The test paper is briefly applied to an agar surface containing bacterial colonies which are subsequently scored individually on the paper by color: yellow indicates the presence of beta-lactamase, dark green its absence, and variegation (yellow and dark green) a mixed population. Concordance of the results of this assay with those of replica plating for antibiotic resistance was over 99%. Hundreds of colonies per plate can be scored quickly and remain viable for further evaluation. The assay appears to be useful for studies of the stability of plasmids encoding beta-lactamases and in cloning with vectors such as pBR322 in which insertion of DNA fragments can be detected by inactivation of the beta-lactamase gene. Whenever the assay is to be used, results should always be confirmed initially by another method, such as replica plating, because the test paper assay does not detect three beta-lactamases (OXA-2, OXA-3, and PSE-2) and also would miss intrinsic penicillin resistance.