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R J Little

Publications and source records attributed to R J Little.

17 recordsLinked to original sources
PubMed1997

Assessment of weighting methodology for the National Comorbidity Survey.

The authors studied weighting adjustments for the National Comorbidity Survey (1990-1992), a large-scale national epidemiologic investigation of the prevalence, risk factors, and consequences of psychiatric morbidity and comorbidity in the United States. Weighting adjustments for differential selection within households, new construction, unit nonresponse, and poststratification were examined separately and in combination. Specific issues addressed included the magnitude of the bias incurred from ignoring the weights, the added variance from weighting and how well this was predicted by simple formulae, and the performance of methods for trimming the weights. Weights had quite modest effects on point estimates of prevalences but resulted in major increases in variance unless trimmed. The weights after trimming and poststratification appeared to work well. It is suggested that the added variance from weighting be carefully monitored in similar surveys. Alternatives to the use of trimming for controlling variance are worth exploring.

Analysis of Variance↗
PubMed1997

Cognitive, behavioral, and motor effects of the NMDA antagonist ketamine in Huntington's disease.

BACKGROUND: Excitotoxicity may contribute to neuronal degeneration in Huntington's disease (HD). N-methyl-D-aspartate (NMDA) receptor antagonists can prevent neuronal degeneration caused by excitotoxicity, but their effects in HD patients are not known. METHODS: We investigated the acute cognitive, behavioral, and motor effects of the NMDA-receptor antagonist ketamine in HD patients. Double-blind infusions of 0.10, 0.40, and 0.60 mg/kg/hr ketamine were given to 10 HD patients on one test day and compared with placebo infusions on a second, identical testing day. Linear mixed-effects models and randomization tests were used to identify whether, and at which dose, a significant change from baseline occurred in outcome variables. RESULTS: We demonstrated that ketamine is well tolerated at low and intermediate subanesthetic doses. Intermediate ketamine doses produced specific decline in memory and verbal fluency. Higher subanesthetic doses caused a significant increase in psychiatric symptoms and impairment of eye movements. CONCLUSIONS: These results describe the spectrum of clinical effects produced by increasing NMDA receptor blockade in HD patients. The clinical effects appearing with higher levels of NMDA receptor blockade can identify the range of doses used in clinical trials of NMDA receptor antagonists.

Adult↗
PubMed1997

Inference for phylogenies under a hybrid parsimony method: evolutionary-symmetric transversion parsimony.

A new method is proposed for inferring topology for evolutionary trees. Existing methods have complementary strengths and weaknesses. Maximum and transversion parsimony are powerful methods, but they lack statistical consistency, that is, they do not always infer the correct tree as the sequence length becomes very large. Evolutionary parsimony overcomes this deficiency, but it may lack sufficient power when sequence length is small (less than 1000 aligned nucleotides; Sinsheimer, Lake, and Little, 1996, Biometrics 52, 193-210). Our proposed method, evolutionary-symmetric transversion parsimony, is a hybrid that retains the consistency of evolutionary parsimony, while increasing power by incorporating a modified form of transversion parsimony within a statistical model. The method requires choice of a parameter gamma that represents the prior probability that symmetric transversion parsimony yields consistent results. Properties of the method are assessed for a variety of choices of gamma in a large simulation study. In general, inference under the evolutionary-symmetric transversion parsimony has more discriminating power than inference under evolutionary parsimony and is better calibrated than inference under symmetric transversion parsimony. The results are quite robust to the choice of gamma, indicating a value of 0.90 as a reasonable overall choice when the true value of gamma ranges between 0.85 to 1.00. Our method is, like evolutionary parsimony and maximum parsimony, computationally straightforward. The same statistical approach can be applied to combine evolutionary parsimony with other inconsistent methods, such as maximum parsimony, but at the expense of more difficult computations.

Animals↗
PubMed1996

Patterns of DSM-III-R alcohol dependence symptom progression in a general population survey.

Age of onset reports obtained retrospectively for each symptom of DSM-III-R alcohol dependence (AD) are used to study patterns of lifetime symptom progression in a large general-population survey of people in the United States. It is shown that symptom progression among a substantial majority of respondents can be summarized as movement across three clusters. Cluster A is defined by symptoms of role impairment/hazardous use (A4), use despite social, psychological or physical problems (A6), and drinking larger amounts or over a longer period of time than intended (A1). Cluster B is defined by tolerance (A7) and impaired control (A2, A3). Cluster C is defined by withdrawal (A8, A9) and giving up activities in order to drink (A5). Clusters are shown to follow a time sequence, with at least one symptom in Cluster A usually occurring first, followed by symptoms in Clusters B and C. In all, 83.4% of the symptom cluster transitions estimated from retrospective age of onset reports are consistent with this progression. Progression to AD is differentially predicted by symptom profiles reported at the age of first symptom onset, with persons reporting Cluster C symptoms most likely to progress subsequently to AD. Furthermore, profiles of AD defined by the highest symptom cluster present at AD onset are differentially predicted by prior personal and parental histories of psychopathology and, among men, are predictive of diagnosis persistence.

Adolescent↗
PubMed1996

Pattern-mixture models for multivariate incomplete data with covariates.

Pattern-mixture models stratify incomplete data by the pattern of missing values and formulate distinct models within each stratum. Pattern-mixture models are developed for analyzing a random sample on continuous variables y(1), y(2) when values of y(2) are nonrandomly missing. Methods for scalar y(1) and y(2) are here generalized to vector y(1) and y(2) with additional fixed covariates x. Parameters in these models are identified by alternative assumptions about the missing-data mechanism. Models may be underidentified (in which case additional assumptions are needed), just-identified, or overidentified. Maximum likelihood and Bayesian methods are developed for the latter two situations, using the EM and SEM algorithms, direct and interactive simulation methods. The methods are illustrated on a data set involving alternative dosage regimens for the treatment of schizophrenia using haloperidol and on a regression example. Sensitivity to alternative assumptions about the missing-data mechanism is assessed, and the new methods are compared with complete-case analysis and maximum likelihood for a probit selection model.

Algorithms↗
PubMed1996

Bayesian hypothesis testing of four-taxon topologies using molecular sequence data.

The reconstruction of phylogenetic trees from molecular sequences presents unusual problems for statistical inference. For example, three possible alternatives must be considered for four taxa when inferring the correct unrooted tree (referred to as a topology). In our view, classical hypothesis testing is poorly suited to this triangular set of alternative hypotheses. In this article, we develop Bayesian inference to determine the posterior probability that a four-taxon topology is correct given the sequence data and the evolutionary parsimony algorithm for phylogenetic reconstruction. We assess the frequency properties of our models in a large simulation study. Bayesian inference under the principles of evolutionary parsimony is shown to be well calibrated with reasonable discriminating power for a wide range of realistic conditions, including conditions that violate the assumptions of evolutionary parsimony.

Base Sequence↗
PubMed1995

Assessing HIV vaccine effects.

It is unlikely that human immunodeficiency virus (HIV) vaccines will create impenetrable barriers to infection. When the barriers to infection are broken, however, vaccine effects on the progression of infection to disease and on the contagiousness of infection could be considerable. The usual outcomes of vaccine trials are either infection or disease. The authors argue that for HIV vaccines, the alternative outcome of contagiousness may be more important. Because of the long incubation period to acquired immunodeficiency syndrome (AIDS), a vaccine trial with AIDS as the outcome would be a long and costly undertaking. Because contagiousness is concentrated into the period of primary infection, vaccine trials assessing contagiousness would not take as long. An approach to assessing vaccine effects on the contagiousness of primary infection while simultaneously assessing protection against infection is presented. It involves randomizing vaccination of couples in whom both individuals are uninfected and one or both have a risk of infection outside the couple. In such a study, the vaccine effect on susceptibility to infection can be estimated from the proportions of vaccinated and unvaccinated couples in whom neither partner is infected. Estimation of the contagiousness effect also uses information on the frequency with which both partners are infected. In areas of the world where heterosexual epidemics are emerging within the context of concurrent partnerships, the randomization of vaccination of couples could increase the efficiency and decrease the costs of vaccine trials.

AIDS Vaccines↗
PubMed1995

Alzheimer and vascular dementias and driving. A prospective road and laboratory study.

OBJECTIVE: To characterize on-the-road, behind-the-wheel driving abilities and related laboratory performances of subjects with mild Alzheimer's disease (AD) and vascular dementia. DESIGN: Prospective, experimental study involving two mild dementia and three age and health control groups. Road test reliability and validity were assessed. SETTING: Greater western Los Angeles. Subjects were enrolled from the community by referral and from the Veterans Affairs dementia and diabetes clinics. PARTICIPANTS: Eighty-seven driving subjects were enrolled; 83 completed the study. A sample of eligible dementia clinic subjects consisting of 15 mild AD patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association probable AD criteria, while 12 met Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and Hachinski diagnostic criteria for multi-infarct dementia (vascular dementia). Clinic control subjects consisted of 15 age-matched patients with diabetes and without a history of stroke or dementia. Community controls consisted of 26 healthy, age-matched, older subjects (> 60 years) and 16 young subjects (20 to 35 years). MAIN OUTCOME MEASURES: Drive score from the Sepulveda (Calif) road test and laboratory measures of attention, perception, and memory. RESULTS: The drive scores in the mild AD group (mean, 22.1; SD, 3.8) and in the vascular dementia group (mean, 24.0; SD, 7.8) differed significantly (P < .001 studentized range test) from the drive scores in the diabetic control group (mean, 31.5; SD, 3.9), the older control group (mean, 32.6; SD, 2.8), and the young control group (mean, 33.6; SD, 3.2). Drive score among the three control groups did not vary significantly. Short-term memory (Sternberg), visual tracking, and Folstein Mini-Mental State Examination scores correlated best with drive score, with a cumulative R2 of 0.68. Drive score and number of collisions and moving violations per 1000 miles driven were negatively correlated (r = -0.38; P < .02). CONCLUSIONS: Based on this study, type and degree of cognitive impairment are better predictors of driving skills than age or medical diagnosis per se. Specific testing protocols for drivers with potential cognitive impairment may detect unsafe drivers more effectively than using age or medical diagnosis alone as criteria for license restriction or revocation.

Adult↗
PubMed1993

Multiple imputation for threshold-crossing data with interval censoring.

Medical statistics often involve measurements of the time when a variable crosses a threshold value. The time to threshold crossing may be the outcome variable in a survival analysis, or a time-dependent covariate in the analysis of a subsequent event. This paper presents new methods for analysing threshold-crossing data that are interval censored in that the time of threshold crossing is known only within a specified interval. Such data typically arise in event-history studies when the threshold is crossed at some time between data-collection points, such as visits to a clinic. We propose methods based on multiple imputation of the threshold-crossing time with use of models that take into account values recorded at the times of visits. We apply the methods to two real data sets, one involving hip replacements and the other on the prostate specific antigen (PSA) assay for prostate cancer. In addition, we compare our methods with the common practice of imputing the threshold-crossing time as the right endpoint of the interval. The two examples require different imputation models, but both lead to simple analyses of the multiply imputed data that automatically take into account variability due to imputation.

Data Interpretation, Statistical↗
PubMed1992

Incomplete data in repeated measures analysis.

Complete (or balanced) repeated measures data arise when all subjects in a study are measured at the same set of time points. Data are often incomplete, because measurements are missed, or the design of the study results in subjects being measured at different sets of time points. This article reviews methods of analysis for incomplete repeated-measures data of this form, from an applied statistician's perspective. Limitations of approaches that (a) ignore between-subject variation, or (b) impute for missing values are discussed. Two methods are advocated that are relatively easy to implement using existing software, namely between-subject analysis of within-subject summary measures, and maximum likelihood based on a model for the data. Methods are applied and compared on four real-data examples with varied analytical objectives.

Adolescent↗
PubMed1987

Peritoneal kinetics in children undergoing continuous ambulatory/cycling peritoneal dialysis.

We present a report on peritoneal kinetics in children undergoing continuous ambulatory/cycling peritoneal dialysis (CAPD/CCPD). The effect of long-term treatment with CAPD/CCPD, peritonitis episodes, and dialysate inflow volume on peritoneal kinetics in children was evaluated. Peritoneal kinetic studies (PKSs) were performed in 47 pediatric patients at different times following initiation of CAPD/CCPD. In 18 of these patients, PKSs were repeated up to four times with an unchanged dialysate inflow volume after up to 55 months of CAPD/CCPD treatment. The PKS consisted of a 120-minute dwell with a 1.5% dextrose dialysate solution. Peritoneal clearance, dialysance, and dialysate to plasma (D/P) concentration ratios were calculated after 30, 60, and 120 minutes. The results of the serial PKSs demonstrate stable peritoneal creatinine and urea-N clearance, dialysance or D/P concentration ratios. Furthermore, there was no adverse effect of 32 peritonitis episodes. Finally, inflow volumes correlated directly with clearances of creatinine (P less than .01), urea-N (P less than .001), and potassium (P less than .001), and there was an inverse relationship to the D/P concentration ratios of creatinine (P less than .01), urea-N (P less than .01), potassium (P less than .01), and uric acid (P less than .01). Thus, CAPD/CCPD is a useful and effective long-term treatment modality for pediatric patients. Maximal dialysate inflow volumes should be provided to enhance peritoneal kinetics.

Adolescent↗
PubMed1982

The statistical analysis of low-level radioactivity in the presence of background counts.

The analysis of low-level or background dominant radioactivity is complicated by the fact that sample net rate of activity above background may be negative, because of random fluctuations. The traditional large sample confidence intervals can contain negative values for the net rate, although we know the net rate is positive. This problem leads to statistically unsound practices such as the reporting of "less than" values when the net value lies below a certain "detectable limit". In this paper we present two Bayesian analyses of the data which take account of the fact that the net rate is positive, and thus always lead to positive estimates and probability intervals for the true underlying rate. The estimates and intervals are compared with classical results for twenty trial data sets.

Background Radiation↗
PubMedDate not supplied

Results of new air caloric testing method among normal subjects. II. Monophasic testing.

A new caloric irrigation method is described. In the new method, the temperature of a continuous aural irrigation is switched between hot and cold values at precisely specified times. The durations of hot and cold pulses have been calculated to produce specific caloric stimulation intensities based on known heat transmission characteristics of the labyrinth area. A brief "washout" irrigation is used to eliminate promptly all caloric stimulation effects at the conclusion of each test. The present study concentrated upon the question of how long the "washout" pulse should be in order to obtain optimum results. Repetitive application of a uniform stimulus intensity to 6 normal subjects indicated that short inter-test intervals can be used without causing vestibular habituation. Prompt removal of the caloric stimulus can be accomplished by proper timing the "washout" phase of the new technique.

Caloric Tests↗