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Biomedical subjects

S G Self

Publications and source records attributed to S G Self.

At least 37 records · Page 2Linked to original sources
PubMed1991

An adaptive weighted log-rank test with application to cancer prevention and screening trials.

A class of adaptive weighted log-rank statistics is described where the vector of weights is chosen in a data-dependent way from a family of "smooth" weight vectors. A parametric family of weight vectors is identified which includes most shapes of weighting vectors that will be near optimal in many cancer prevention and screening trials. This family of weight vectors is used in an application of the proposed method to data from a breast cancer screening trial. Results from a small simulation study comparing the power of the adaptive statistic to that of the unweighted log-rank statistic are presented.

Biometry↗
PubMed1991

On estimating HLA/disease association with application to a study of aplastic anemia.

A multiplicative model is described relating HLA typing information to disease incidence. A likelihood-based method for estimating parameters in this model is proposed for use with data sets in which HLA haplotype information is available on a series of cases and their parents. This approach is extended to incorporate information from a matched control series for the purpose of estimating HLA and environmental risk factor effects simultaneously. The method is applied to data from aplastic anemia patients treated by bone marrow transplantation and the results are compared to unmatched case-control analyses using the same case series and several different control series.

Anemia, Aplastic↗
PubMed1990

The Cox proportional hazards model with change point: an epidemiologic application.

In this paper, we develop the Cox proportional hazards model with special structured time-dependent covariates in the context of prospective epidemiologic studies. Our model possesses the following two features: (i) different relative risk parameters are allowed for early versus late onset of the disease of interest; (ii) an additional parameter is introduced so that specification is not required for the time (age) at which a change of the magnitude of the relative risks takes place, the so-called change point. Some difficulties with statistical inference for the proposed model are briefly discussed, and the large-sample distribution of a test for no change point is derived. As an illustration, we apply the model to a set of data gathered on a group of white male medical students of The Johns Hopkins Medical School enrolled between 1948 and 1964. We examine the hypothesis that the effect of reactivity to the cold pressor test may vary with early versus late onset of hypertension.

Biometry↗
PubMed1989

Further results on covariate measurement errors in cohort studies with time to response data.

The impact of covariate measurement errors on the estimation of relative risk regression parameters is discussed. First the dependence of the induced relative risk process on the cumulative baseline failure rate function is noted. Next induced relative risk models under some specific failure time and measurement error models are described, including the much simplified models that are appropriate under a 'rare disease' assumption. The presentation then turns to the joint estimation of relative risk parameters of primary interest along with measurement error parameters. A partial likelihood product is proposed for such estimation and asymptotic properties are indicated. Guidance is also presented as to the appropriate size of a 'validation' sample relative to the full cohort size. Finally some more general considerations are presented as to the usefulness and interpretation of deattenuated regression coefficients.

Analysis of Variance↗
PubMed1989

Modelling paired survival data with covariates.

The objective of this paper is to consider the parametric analysis of paired censored survival data when additional covariate information is available, as in the Diabetic Retinopathy Study, which assessed the effectiveness of laser photocoagulation in delaying loss of visual acuity. Our first approach is to extend the fully parametric model of Clayton (1978, Biometrika 65, 141-151) to incorporate covariate information. Our second approach is to obtain parameter estimates from an independence working model together with robust variance estimates. The approaches are compared in terms of efficiency and computational considerations. A fundamental consideration in choosing a strategy for the analysis of paired survival data is whether the correlation within a pair is a nuisance parameter or a parameter of intrinsic scientific interest. The approaches are illustrated with the Diabetic Retinopathy Study.

Actuarial Analysis↗
PubMed1989

Minimal risk of chronic renal dysfunction in marrow transplant recipients treated with cyclosporine for 6 months.

To determine whether 6 months of cyclosporine therapy is associated with chronic renal dysfunction, we evaluated serum creatinine concentrations 1 year post-transplant in 82 marrow transplant recipients randomized to receive either cyclosporine (n = 40) or methotrexate (n = 42) as graft-versus-host disease (GVHD) prophylaxis. Nine patients in the methotrexate group were later given cyclosporine as treatment for acute or chronic GVHD (methotrexate----cyclosporine). Cyclosporine prophylaxis was started on the day before marrow infusion, given at full doses until day 50, then gradually tapered and discontinued by day 180. Methotrexate prophylaxis was started on day 1 and given intermittently until day 102. Patients in the cyclosporine and methotrexate----cyclosporine groups had significantly higher mean serum creatinine values during the first 100 days post-transplant than methotrexate-treated patients, but by 1 year mean serum creatinine values were not significantly different between the three groups. Serum creatinine values at 1 year were also not significantly different from baseline values in each of the groups. None of the patients who had their cyclosporine discontinued by day 180 developed chronic renal dysfunction, defined as a doubling of the baseline serum creatinine at 1 year. We conclude that chronic renal dysfunction occurs rarely in marrow transplant recipients treated with 6 months of cyclosporine and when it does occur, it appears to have minimal clinical significance.

Bone Marrow Transplantation↗
PubMed1989

On testing departure from the binomial and multinomial assumptions.

This paper is concerned with testing the multinomial (binomial) assumption against the Dirichlet-multinomial (beta-binomial) alternatives. In particular, we discuss the distribution of the asymptotic likelihood ratio (LR) test and obtain the C(alpha) goodness-of-fit test statistic. The inadequacy of the regular chi-square approximation to the LR test is supported by some Monte Carlo experiments. The C(alpha) test is recommended based on empirical significance level and power and also computational simplicity. Two examples are given.

Computer Simulation↗
PubMed1988

Serum cyclosporine concentration and risk of acute graft-versus-host disease after allogeneic marrow transplantation.

To determine the relation between the serum cyclosporine concentration and the risk of acute graft-versus-host disease (GVHD), we studied 179 recipients of bone marrow grafts from HLA-identical sibling donors who received prophylaxis with cyclosporine, either by itself or combined with methotrexate. Cyclosporine was given either orally or intravenously at full doses from the day before transplantation until day 50; it was then tapered off and discontinued on day 180. Trough concentrations of serum cyclosporine were measured by radioimmunoassay. The relation between patients' characteristics and the risk of acute GVHD was analyzed with a relative-risk regression model. In 66 patients (37 percent), grades II to IV of acute GVHD developed 7 to 66 days (median, 13) after transplantation. The trough cyclosporine concentration for a given week was significantly associated with the risk that acute GVHD would develop during the following week. The relative risks were 0.7 (i.e., there was a 30 percent reduction in risk) for every increase of 100 ng per milliliter in cyclosporine concentration and 1.0, 0.60, and 0.20 for concentrations of less than 100, 100 to 199, and 200 or more ng per milliliter, respectively (P less than 0.01). A patient's age, prophylaxis regimen, and year of transplantation also influenced the risk of acute GVHD significantly. These data indicate that low cyclosporine concentrations can be a cause of treatment failure and that concentrations should be monitored in recipients of marrow transplants.

Acute Disease↗
PubMed1987

Monitoring cyclosporin concentrations in marrow transplant recipients: comparison of two assay methods.

Renal dysfunction is the major dose-limiting toxicity associated with cyclosporin therapy. We have previously shown in patients undergoing allogeneic bone marrow transplantation that serum cyclosporin concentrations, as measured by radioimmunoassay (RIA), correlate significantly with the development of renal dysfunction. However, since the RIA measures both parent drug and metabolites, the relative role of each in the development of nephrotoxicity could not be determined. Therefore, we re-measured cyclosporin concentrations in the same serum samples by high-performance liquid chromatography (h.p.l.c.). Serum cyclosporin concentrations of less than 50, 50-100 and greater than 100 ng/ml, as measured by h.p.l.c., were considered equivalent to cyclosporin concentrations of less than 150, 150-250 and greater than 250 ng/ml, as measured by RIA. Contrary to results by RIA, cyclosporin concentrations measured by h.p.l.c. did not significantly correlate with renal dysfunction, which suggests that measurement of serum cyclosporin concentrations by h.p.l.c. provides no clinical advantage to RIA for monitoring cyclosporin concentrations to prevent renal dysfunction.

Adolescent↗
PubMed1986

Linear rank tests for interval-censored data with application to PCB levels in adipose tissue of transformer repair workers.

Linear rank statistics are described for testing for differences between groups when the data are interval-censored. The statistics are closely related to those described by Prentice (1978, Biometrika 65, 167-179) for right-censored data. Problems in calculating the statistics are discussed and several approaches to computation including estimation of the efficient rank scores are described. Results from a small simulation study are presented. The methods are applied to data from a study relating tissue levels of PCBs to occupational exposure.

Adipose Tissue↗
PubMed1985

Familial aggregation in chronic obstructive pulmonary disease: use of the loglinear model to analyze intermediate environmental and genetic risk factors.

To examine the contribution of environmental and genetic risk factors to familial aggregation in chronic obstructive pulmonary disease (COPD), 325 first-degree (1d) relatives and 56 spouses of 150 COPD patients were compared with 222 1d relatives and 49 spouses of 107 nonpulmonary patient controls for the prevalence of two clinical outcomes: 1) airways obstruction (AO; 1-sec forced expiratory volume less than 68% of forced vital capacity) and 2) chronic bronchitis (CB; cough and sputum for 3+ months per year for 2+ years). The loglinear model was used to study direct and indirect (ie, those mediated by other risk factors) components of familial aggregation. Three risk factors were found to be independently associated with CB and/or AO: alpha 1-antitrypsin deficiency (PiZ allele), personal cigarette smoking, and parental cigarette smoking. Because 1d relatives of COPD patients were more likely to have a PiZ allele, be heavy smokers (1+ packs per day), and be exposed to parental smoking than 1d relatives of controls, these three factors also constitute indirect components of familial aggregation. However, after controlling for the three factors, 1d relatives of COPD patients were more likely to have AO and CB than 1d relatives of controls (direct component). This direct component might have a genetic basis, because no such association was found when spouses instead of 1d relatives were compared. Thus, both shared environmental factors (personal and passive smoking) and shared genetic factors (alpha 1-antitrypsin and a possible direct genetic component) contribute to familial aggregation in COPD. The loglinear model provides a useful tool for analyzing familial aggregation in diseases of multifactorial etiology.

Biometry↗
PubMed1985

Use of robust variance components models to analyse triglyceride data in families.

A robust approach for analysis of variance components models is presented which does not rely on the assumption of multivariate normality for its validity. This approach uses the multivariated normal distribution as a 'working model' but obtains standard errors for the final estimators which do not depend on this underlying distribution. By using the observed variance in the first derivatives of the multivariate normal 'working model' to modify the conventional score test, hypotheses regarding specific components can also be tested without relying directly on the assumption of multivariate normality. A special case is presented where both the modified score test and the likelihood ratio test are equally robust, and simulated data are used to illustrate this situation. Measurements of triglyceride levels in 391 individuals in 60 families randomly selected from the membership of a health maintenance organization are used to illustrate this robust approach to variance components.

Genetic Variation↗
PubMed1985

The effect of additional follow-up and accrual on survival time data.

A method called partial completion is proposed for predicting the gain in precision of the Kaplan-Meier survival curve associated with additional follow-up and accrual. This is accomplished by using the initial data to predict the numbers of patients who would be at risk at the observed death times by the end of the proposed second follow-up period. A consistency result ensures that the predictors will be accurate in large samples while simulation results suggest that the predictors are accurate with moderate sample sizes. The procedures are applied to a bone marrow transplant study and the Channing House data set.

Biometry↗
PubMed1983

Assessment of variance components models on pedigrees using cholesterol, low-density, and high-density lipoprotein measurements.

Plasma total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) measurements on 402 individuals in 62 randomly selected families from the Columbia Medical Plan population were used to select the "best" model among a series of multifactorial models using the maximum likelihood method described by Lange et al [1976]. These models included both genetic and nongenetic components of variance. The most parsimonious model for each trait was selected and examined using a goodness-of-fit statistic designed by Hopper and Mathews [1982] to test the assumptions of this technique. A simple additive genetic model was the most plausible for all three measurements, suggesting a strong role for genetic factors in determining lipid and lipoprotein levels in these data. Goodness-of-fit statistics for these models were examined and showed little evidence of deviation from the assumption of multivariate normality within pedigrees. This approach of selecting the most parsimonious model among a series of competing models and then assessing its goodness-of-fit has many applications in studying familial aggregation of quantitative traits.

Adult↗
PubMed1983

The use of life tables and survival analysis in testing genetic hypotheses, with an application to Alzheimer's disease.

Because of the late onset of some neuropsychiatric disorders suspected to be under genetic influence, such as Alzheimer's disease, standard techniques for testing genetic hypotheses are difficult to apply to clinical data. The statistical aspects of life table methods and survival probability estimators which can be used to test such hypotheses have been neglected in the psychiatric literature. Two techniques of this kind, the Weinberg morbidity table and the Kaplan-Meier product limit estimator, are applied to real and simulated data. As estimators of lifetime incidence these methods yield roughly equivalent results for both types of data, although from a theoretical standpoint the original Weinberg estimator appears to suffer from logical defects. Parametric models may offer more definitive results, particularly when an estimator of segregation ratio is required. The clinical data in this report were gathered by interviewing relatives of Alzheimer's disease patients sampled through a nursing home survey in metropolitan Baltimore, Maryland during 1980.

Actuarial Analysis↗
PubMed1982

Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of myasthenia gravis.

The pathogenesis of myasthenia gravis involves a humorally mediated autoimmune attack directed against acetylcholine receptors of skeletal muscles. Antibodies against acetylcholine receptors are detected in the serum of more than 80 per cent of patients, but the antibody titers correspond poorly with the severity of disease. To distinguish between antibody titers and antibody activity, we measured the ability of serum immunoglobulin from 49 patients to induce accelerated degradation or blockade of the binding sites of acetylcholine receptors, using a mammalian skeletal-muscle tissue-culture system. Immunoglobulin from 41 of 45 patients tested (91 per cent) increased the rate of degradation of acetylcholine receptors, and the relative increase in the degradation rate corresponded closely (P less than 0.001) with clinical status. Immunoglobulin from 42 of 48 patients tested (88 per cent) produced blockade of receptors, and the extent of the blockade also corresponded with clinical status (P less than 0.001). An index of the combined activities of the immunoglobulin in accelerating degradation and producing blockade of acetylcholine receptors was elevated in 43 of 44 patients (98 per cent) whose immunoglobulins were tested for both activities; this index predicted the patients' clinical status significantly better (P less than 0.001) than either measure alone. This finding suggests that the functional ability of antibodies to decrease the number of available acetylcholine receptors by these two mechanisms is clinically relevant in the pathogenesis of myasthenia gravis.

Autoantibodies↗
PubMed1978

Heritability of quasi-continuous skeletal traits in a randombred population of house mice.

Heritabilities of 11 quasi-continuous skeletal traits were estimated in randombred house mice of three separate ages (1, 3, and 5 months). Three separate methods--regression, maximum likelihood correlation, and Falconer's Method--were used to obtain heritabilities for each of the separate age groups. Significant differences in the incidences of seven of the skeletal traits were found among ages, but they did not affect the heritability estimates, these estimates being pooled over ages. Heritabilities calcuated from female parents were consistently higher (by about 13%) than those from male parents, indicating the presence of maternal effects. Mid-parent estimates made by all three methods gave very similar mean levels (0.17--0.20). Although low, this level compared favorably with that expected on the basis of previously estimated rates of accumulation of genetic variance. Maternal effects estimated from full sib correlations averaged 0.08.

Aging↗