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Biomedical subjects

C E McCulloch

Publications and source records attributed to C E McCulloch.

17 recordsLinked to original sources
PubMed2002

Discovering subpopulation structure with latent class mixed models.

The linear mixed model is a well-known method for incorporating heterogeneity (for example, subject-to-subject variation) into a statistical analysis for continuous responses. However heterogeneity cannot always be fully captured by the usual assumptions of normally distributed random effects. Latent class mixed models offer a way of incorporating additional heterogeneity which can be used to uncover distinct subpopulations, to incorporate correlated non-normally distributed outcomes and to classify individuals. The methodology is motivated with examples in health care studies and a detailed illustration is drawn from the Nutritional Prevention of Cancer trials. Latent class models are used with longitudinal data on prostate specific antigen (PSA) as well as incidence of prostate cancer. The models are extended to accommodate prostate cancer as a survival endpoint; this is compared to treating it as a binary endpoint. Four subpopulations are identified which differ both with regard to their PSA trajectories and their incidence rates of prostate cancer.

Adolescent↗
PubMed2001

Genetic control of horizontal virus transmission in the chestnut blight fungus, Cryphonectria parasitica.

Vegetative incompatibility in fungi has long been known to reduce the transmission of viruses between individuals, but the barrier to transmission is incomplete. In replicated laboratory assays, we showed conclusively that the transmission of viruses between individuals of the chestnut blight fungus Cryphonectria parasitica is controlled primarily by vegetative incompatibility (vic) genes. By replicating vic genotypes in independent fungal isolates, we quantified the effect of heteroallelism at each of six vic loci on virus transmission. Transmission occurs with 100% frequency when donor and recipient isolates have the same vic genotypes, but heteroallelism at one or more vic loci generally reduces virus transmission. Transmission was variable among single heteroallelic loci. At the extremes, heteroallelism at vic4 had no effect on virus transmission, but transmission occurred in only 21% of pairings that were heteroallelic at vic2. Intermediate frequencies of transmission were observed when vic3 and vic6 were heteroallelic (76 and 32%, respectively). When vic1, vic2, and vic7 were heteroallelic, the frequency of transmission depended on which alleles were present in the donor and the recipient. The effect of heteroallelism at two vic loci was mostly additive, although small but statistically significant interactions (epistasis) were observed in four pairs of vic loci. A logistic regression model was developed to predict the probability of virus transmission between vic genotypes. Heteroallelism at vic loci, asymmetry, and epistasis were the dominant factors controlling transmission, but host genetic background also was statistically significant, indicating that vic genes alone cannot explain all the variation in virus transmission. Predictions from the logistic regression model were highly correlated to independent transmission tests with field isolates. Our model can be used to estimate horizontal transmission rates as a function of host genetics in natural populations of C. parasitica.

Alleles↗
PubMed2001

Self-efficacy, depressive symptoms, and patients' expectations predict outcomes in asthma.

BACKGROUND: Certain psychosocial variables are relatively unexplored as possible predictors of asthma outcomes. OBJECTIVE: To determine if asthma self-efficacy, depressive symptoms, and unrealistic expectations predict urgent care use and change in health-related quality of life measured by the Asthma Quality of Life Questionnaire and the SF-36 during 2 years. RESEARCH DESIGN: Prospective cohort study in a primary care internal medicine practice at a tertiary care center in New York City. PATIENTS: Adults with moderate asthma who were fluent in either English or Spanish. MEASUREMENTS: At enrollment patients were interviewed in-person and completed a series of questionnaires including the Asthma Quality of Life Questionnaire (AQLQ), the SF-36, the Asthma Self-efficacy Scale, the Geriatric Depression Scale, and open-ended questions regarding their expectations of treatment. Patients also completed the AQLQ and SF-36 at various time intervals throughout the study and were interviewed by telephone every 3 months to record recent hospitalizations, emergency department visits and nonroutine office visits for asthma. RESULTS: A total of 224 patients were followed for a mean of 23.8 months. In hierarchical analysis, independent predictors of lower AQLQ scores were less self-efficacy, more depressive symptoms, expecting to be cured of asthma, requiring methylxanthines, being Hispanic or black, and having difficult or very difficult access to asthma care (all at P <0.05). Similar predictors were found for lower SF-36 scores. Another outcome, use of urgent care, was required by 60% of patients during the study period. Predictors of using urgent care were having more depressive symptoms, expecting a cure, being female, requiring oral beta-agonists, and having a history of prior hospitalizations for asthma (all at P <0.05). CONCLUSIONS: Less asthma self-efficacy, more depressive symptoms, and unrealistic expectations predict worse asthma outcomes. These relatively unexplored patient-centered variables in asthma are potentially modifiable and may offer new ways to intervene to improve asthma outcomes.

Adolescent↗
PubMed2000

A latent class mixed model for analysing biomarker trajectories with irregularly scheduled observations.

This paper considers a latent class model to uncover subpopulation structure for both biomarker trajectories and the probability of disease outcome in highly unbalanced longitudinal data. A specific pattern of trajectories can be viewed as a latent class in a finite mixture where membership in latent classes is modelled with a polychotomous logistic regression. The biomarker trajectories within a latent class are described by a linear mixed model with possibly time-dependent covariates and the probabilities of disease outcome are estimated via a class specific model. Thus the method characterizes biomarker trajectory patterns to unveil the relationship between trajectories and outcomes of disease. The coefficients for the model are estimated via a generalized EM (GEM) algorithm, a natural tool to use when latent classes and random coefficients are present. Standard errors of the coefficients are calculated using a parametric bootstrap. The model fitting procedure is illustrated with data from the Nutritional Prevention of Cancer trials; we use prostate specific antigen (PSA) as the biomarker for prostate cancer and the goal is to examine trajectories of PSA serial readings in individual subjects in connection with incidence of prostate cancer.

Adolescent↗
PubMed2000

Simultaneously model-unbiased, design-unbiased estimation.

This paper proposes a class of inferential procedures (incorporating both design and estimation elements) that yield estimates of means that are simultaneously model unbiased and design unbiased. Classical regression procedures yield conditionally unbiased estimators for the mean (conditioning on the model and choice of observation points). In contrast, design-based methods yield estimators that are unconditionally unbiased on matter what the form of the underlying model. Variance properties of the proposed class are examined, and applications to bioavailability, water quality from mine run-off, and finite population regression estimation are considered. The proposed procedures perform well, especially in the typical case where a model is only approximately correct.

Animals↗
PubMed1999

Modeling heterogeneity in nest survival data.

Current statistical methods for estimating nest survival rates assume that nests are identical in their propensity to succeed. However, there are several biological reasons to question this assumption. For example, experience of the nest builder, number of nest helpers, genetic fitness of individuals, and site effects may contribute to an inherent disparity between nests with respect to their daily mortality rates. Ignoring such heterogeneity can lead to incorrect survival estimates. Our results show that constant survival models can seriously underestimate overall survival in the presence of heterogeneity. This paper presents a flexible random-effects approach to model heterogeneous nest survival data. We illustrate our methods through data on redwing blackbirds.

Animals↗
PubMed1999

Effects of milk fever, ketosis, and lameness on milk yield in dairy cows.

The effects of milk fever, ketosis, and lameness were studied using data from 23,416 Finnish Ayrshire cows that calved in 1993 and were followed for one lactation (i.e., until culling or the next calving). Monthly test day milk yields were treated as repeated measurements within a cow in a mixed model analysis. Disease index variables were created to relate the timing of a disease to the measures of test day milk. Statistical models for each parity and disease included fixed effects of calving season, stage of lactation, and disease index. An autoregressive correlation structure was used to model the association among the repeated measurements. The milk yield of cows contracting milk fever was affected for a period of 4 to 6 wk after calving; the loss ranged from 1.1 to 2.9 kg/d, depending on parity and the time elapsed after milk fever diagnosis. Despite the loss, cows with milk fever produced 1.1 to 1.7 kg more milk/d than did healthy cows. Milk yield started to decline 2 to 4 wk before the diagnosis of ketosis and continued to decline for a varying time period after it. The daily milk loss was greatest within the 2 wk after the diagnosis, varying from 3.0 to 5.3 kg/d, depending on parity. Cows in parity 4 or higher were most severely affected by ketosis; the average total loss per cow was 353.4 kg. Lameness also affected milk yield; milk loss of cows diagnosed with foot and leg disorders varied between 1.5 and 2.8 kg/d during the first 2 wk after the diagnosis.

Animals↗
PubMed1999

Effects of clinical mastitis on milk yield in dairy cows.

The effect of clinical mastitis on milk yield was studied in 24,276 Finnish Ayrshire cows that calved in 1993 and were followed for one lactation (i.e., until culling or the next calving). Cows that had only mastitis, but no other diseases, and cows that had no diseases (healthy cows) during the lactation were included in the study. Monthly test day milk yields were treated as repeated measurements within an animal in a mixed model analysis. Mastitis index categories were created to relate the timing of mastitis to the test day milk measures. Statistical models (a separate model for each parity) included fixed effects of calving season, stage of lactation, and mastitis index. An autoregressive correlation structure was used to model the association among the repeated measurements. The effect of mastitis occurring at different periods during the lactation was studied. The daily loss during the first 2 wk after the occurrence of mastitis varied from 1.0 to 2.5 kg, and the total loss over the entire lactation varied from 110 to 552 kg and depended on parity and the time of mastitis occurrence. Regardless of the time of occurrence during the lactation, mastitis had a long-lasting effect on milk yield; cows with mastitis did not reach their premastitis milk yields during the remainder of the lactation after onset of the disease.

Animals↗
PubMed1996

Cross-sectional evaluation of environmental, host, and management factors associated with risk of seropositivity to Ehrlichia risticii in horses of New York state.

OBJECTIVES: To locate counties within New York state with a high seroprevalence among the equine population, to determine host, management, and environmental factors that were associated with seropositivity to Ehrlichia risticii, and to determine evidence for arthropod- or helminth-mediated transmission of E risticii to horses. DESIGN: Cross-sectional study. SAMPLE POPULATION: A random sample of 3,000 of the 39,000 equine operations in New York state was selected, and 2,587 horses from 511 operations were tested. PROCEDURE: Blood samples were collected from horses and tested for seropositivity, using the indirect fluorescent antibody technique. Data on each horse and each farm's management were obtained by personal interview. The significance of each factor on the risk of seropositivity was evaluated, using mixed-effect logistic regression. RESULTS: The seroprevalence among E risticii-nonvaccinated horses was 7.3%. The county-specific seroprevalence ranged from 0 to 27%, with higher-risk counties located at low elevation. Farms at higher risk for having seropositive horses were located predominately at low elevation with no bodies of water nearby. Risk of seropositivity was associated with time spent in a stall or run-in shed, with frequency of application of fly spray, and, depending on duration of residency at the farm, with frequency of deworming with benzimidazole and pyrantel. Standardbreds were 2 to 3 times more likely to have been exposed, compared with Thoroughbreds. Depending on duration of residency at the farm, male and middle-age horses were at higher risk. Up to 32% of the variance for a horse to test seropositive for E risticii on the logit scale was attributable to farm-level random effects, but the nested social group random effect was not significant. CONCLUSIONS: Arthropods and helminths may have a role in the transmission of this disease. Several management factors may directly or indirectly modify the risk of exposure to E risticii, allowing for the possibility of additional control measures besides traditional vaccination strategies.

Age Factors↗
PubMed1995

Multiplicative factors for estimation of daily milk and component yields from single morning or afternoon tests.

Prediction of daily yield from single a.m. or p.m. milkings requires factors that are the reciprocal of the proportion of total yield expected from single milkings given the milking interval. Further adjustments to estimated milk yield account for DIM. Factors used by the Cornell Dairy Records Processing Lab were estimated from data collected from August 1983 to November 1984. These factors appear to be biased. Inconsistent estimates of daily yield were observed monthly. New factors were developed using recent data. Factors from a.m. milkings for milk and protein yield were smaller than those currently in use. The reverse was true for fat yield. Covariants for DIM were larger than those currently used. Differences were observed when factors using data with known and assumed milking intervals were compared. Factors for a.m. milkings with known intervals were smaller than those from p.m. milkings with the same known intervals. Use of covariants for DIM were compared with covariants for single milk yield. The latter explained more variation in yield. Factors were tested on independent data. New factors with covariants for single milk yield performed best for estimation of total daily yield.

Animals↗
PubMed1994

On the likelihood ratio test statistic for the number of components in a normal mixture of unequal variances.

An important but difficult problem in practice is to determine the number of components in a normal mixture model with unequal variances. When the likelihood ratio test statistic--21og lambda is used, it is unbounded above and fails to satisfy standard regularity conditions. A restricted maximization procedure must therefore be used, which makes the procedure ad hoc. A consequence of this may explain the discrepancies among the simulation results of previous investigations.

Algorithms↗
PubMed1992

When does it pay to break the matches for analysis of a matched-pairs design?

Two methods of analysis are compared to estimate the treatment effect of a comparative study where each treated individual is matched with a single control at the design stage. The usual matched-pairs analysis accounts for the pairing directly in its model, whereas regression adjustment ignores the matching but instead models the pairing using a set of covariates. For a normal linear model, the estimated treatment effect from the matched-pairs analysis (paired t-test) is more efficient. For a Bernoulli logistic model, matched-pairs analysis performs better when the sample size is small, but is inferior to logistic regression for large sample sizes.

Clinical Trials as Topic↗
PubMed1991

Associations between breast cancer, plasma triglycerides, and cholesterol.

A case-control study investigating the association between plasma lipids and breast cancer was conducted among women aged 30-80 in Buffalo, NY. All eligible women from a large breast clinic and two area physicians' offices were requested to participate over a one-year period. Subjects completed a health questionnaire and donated a fasting blood sample prior to diagnostic breast biopsies. The 83 women found to have breast cancer (cases) had significantly higher plasma triglyceride values than did the 113 women found not to have breast cancer (controls). Lower plasma beta-carotene values were associated with breast cancer, but only in those women with elevated triglyceride or cholesterol. Plasma cholesterol values were lower in those breast cancer cases presenting with more advanced stages of cancer, suggesting that metabolic effects of clinical and preclinical breast cancer may lower cholesterol levels. Although the limitations of case-control studies are well-recognized, these data suggest an etiologic role for plasma triglycerides and beta-carotene or for related dietary factors.

Adult↗
PubMed1990

Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A.

A case-control study of breast cancer was conducted in Buffalo. Participants completed a food frequency questionnaire and donated a fasting blood sample before definitive workup for breast masses. Dietary and plasma concentrations of carotenoids and retinol for 83 women found to have breast cancer were compared with those of 113 women found to be free of breast cancer (control subjects). There were no case-control differences in dietary estimates of vitamin A intake or in plasma alpha-carotene and lycopene. However, subjects with breast cancer had lower concentrations of plasma beta-carotene than did control subjects (P = 0.02). There was no overall association between plasma retinol and breast cancer but a positive relationship was observed between retinol and breast cancer in the subgroup with low beta-carotene values. These results suggest that low plasma beta-carotene is associated with increased risk of breast cancer. Other studies will need to determine whether low carotene concentrations are a subtle effect of the disease or might be causally related to breast cancer.

Adult↗
PubMed1989

Epidemiology of metabolic disorders in dairy cattle: association among host characteristics, disease, and production.

Logistic regression was used to investigate the effects of host characteristics, production, and 23 veterinary diagnoses on the odds of contracting seven metabolic disorders among 61,124 Finnish Ayrshire cows that calved during 1983. Cows in higher producing herds were at increased risk of parturient paresis, udder edema, and ketosis. Cows that had higher previous yields were at increased risk of parturient and nonparturient paresis and ketosis. All of the metabolic disorders except udder edema were directly interrelated. Dystocia, prolapsed uterus, other infertility, and abortion were not risk factors for any of the seven metabolic disorders; however, retained placenta, early metritis, traumatic reticuloperitonitis, acute and chronic mastitis, and foot or leg injury each were direct risk factors for at least two metabolic disorders.

Acidosis↗
PubMed1984

Sorption of radiocesium by active silica.

Cement and cement components have previously been shown to exhibit negligible sorption for cesium. Pyrogenic silica has been examined as an additive to cement materials for its ability to reduce the leachability of cesium and to provide a host material with permanent sorption sites. The incorporation of silica into cement composites can also improve the physical characteristics and strength of these materials as long ages. At neutral pH values, there is significant sorption of cesium by silica, but in high pH regimes, such as occur in cement environments, initial sorption is enhanced but this high level of sorption is followed by a gradual release of Cs. This apparent desorption is due to the consumption of SiO2 by Ca(OH)2 to form products which have little sorption potential for cesium. If, however, sufficient SiO2 is added to the system initially such that an excess remains after satisfying the demands of the Ca(OH)2 reaction, permanent sorption sites for cesium may be created.

Calcium Hydroxide↗