Generalized variance component models for clustered categorical response variables

A generalized variance component model is proposed for the analysis of a categorical response variable with extra-multinomial variation. Categorical data obtained from research designs such as randomized multicenter clinical trials or complex sample surveys with clustering frequently exhibit extra-variation resulting from intracluster correlation. General correlation patterns are accounted for by utilizing a mixed-effects modelling approach, estimating the cluster variance components through the method of moments and modelling functions of the observed proportions through the use of estimating equations. A flexible set of assumptions characterizing the underlying covariance structure for the proportions can be accommodated. The importance of accounting for extra-variation when performing hypothesis tests is highlighted with an application to data from a multi-investigator clinical trial.     

Developmental interactions between sweat glands and the sympathetic neurons which innervate them: effects of delayed innervation on neurotransmitter plasticity and gland maturation

The neurotransmitter properties of the sympathetic innervation of sweat glands in rat footpads have previously been shown to undergo a striking change during development. When axons first reach the developing glands, they contain catecholamine histofluorescence and immunoreactivity for catecholamine synthetic enzymes. As the glands and their innervation mature, catecholamines disappear and cholinergic and peptidergic properties appear. Final maturation of the sweat glands, assayed by secretory competence, is correlated temporally with the development of cholinergic function in the innervation. To determine if the neurotransmitter phenotype of sympathetic neurons developing in vivo is plastic, if sympathetic targets can play a role in determining neurotransmitter properties of the neurons which innervate them, and if gland maturation is dependent upon its innervation, the normal developmental interaction between sweat glands and their innervation was disrupted. This was accomplished by a single injection of 6-hydroxy-dopamine (6-OHDA) on Postnatal Day 2. Following this treatment, the arrival of noradrenergic sympathetic axons at the developing glands was delayed 7 to 10 days. Like the gland innervation of normal rats, the axons which innervated the sweat glands of 6-OHDA-treated animals acquired cholinergic function and their expression of endogenous catecholamines declined. The change in neurotransmitter properties, however, occurred later in development than in untreated animals and was not always complete. Even in adult animals, some fibers continued to express endogenous catecholamines and many nerve terminals contained a small proportion of small granular vesicles after permanganate fixation. The gland innervation in the 6-OHDA-treated animals also differed from that of normal rats in that immunoreactivity for VIP was not expressed in the majority of glands. It seems likely that following treatment with 6-OHDA sweat glands were innervated both by neurons that would normally have done so and by neurons that would normally have innervated other, noradrenergic targets in the footpads, such as blood vessels. Contact with sweat glands, therefore, appears to suppress noradrenergic function and induce cholinergic function not only in the neurons which normally innervate the glands but also in neurons which ordinarily innervate other targets. Effects of delayed innervation were also observed on target development. The appearance of sensitivity to cholinergic agonists by the sweat glands was coupled with the onset of cholinergic transmission.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of a fat and ground maize supplement on feed intake and digestion by cattle consuming bermudagrass hay (Cynodon dactylon)

Five beef cows (450 kg) and five Holstein steers (254 kg) were used in two Latin square experiments to determine the effects on intake and digestion of supplementing bermudagrass (Cynodon dactylon) hay with maize and fat, singly and in combination, and to compare fat poured on hay with fat mixed with maize. The cows received hay at 1.0% of their body weight (BW) per day alone (control) or with ground maize (0.49% BW) and/or fat (0.054% BW, beef tallow). Treatments were control (C), maize alone (MZ), fat poured on hay alone (PF), maize plus poured fat (MZ-PF) and maize mixed with fat (MZ-MF). Calcium carbonate (0.011% BW) was given to all supplemented animals. Mean ruminal fluid protozoal counts were higher with than without supplements (P < 0.05), for MZ than for PF, and for simultaneous vs. singular offering of maize and fat (P < 0.05). Flows of microbial organic matter and nitrogen at the duodenum were higher with than without supplements, for MZ than for PF, and for MZ-MF than for MZ-PF. Digestion of neutral detergent fiber in the whole tract declined with supplementation, but differences among supplement treatments were not significant. In the second study, steers received hay ad libitum and higher levels of supplements (maize 0.89, fat 0.099 and calcium carbonate 0.021% BW day⁻¹). Total dry matter intake was C 5.86, MZ 7.86, PF 6.83, MZ-PF 7.90 and MZ-MF 7.75 kg day⁻¹, being affected by supplementation and higher for MZ than PF (P < 0.05). Total tract neutral detergent fiber digestion was C 72.0, MZ 67.0, PF 69.2, MZ-PF 65.1, and MZ-MF 61.0%, and was depressed by supplementation and lower for simultaneous vs. singular supplementation with maize and fat (P < 0.05). In conclusion, there were no advantages in intake or digestion to adding fat to supplemental maize either separately or mixed as compared with supplementation with maize alone.