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Biomedical subjects

P J Diggle

Publications and source records attributed to P J Diggle.

At least 19 recordsLinked to original sources
PubMed1999

Regular fluctuations in growth hormone (GH) release determine normal human growth.

Growth hormone (GH) is the principal hormone associated with growth through childhood, but in a normal child the amount of GH secretion does not appear to be critical in the generation of normal growth rates. We have assessed the relationship between growth and urinary GH (uGH) output in a longitudinal study of 29 healthy prepubertal schoolchildren (13 male, 16 female; age 5.7-7.8 years) over 1 year. Height and uGH were measured three times a week. Individual height velocity curves were derived using non-linear regression. Growth was expressed in terms of the total increment over the year (DeltaHt, cm), height velocity standard deviation score (HVSDS) and the average size of individual growth spurts. Urinary GH data (ng) were expressed as a weekly average. Mean uGH did not correlate with stature or growth over the year. However, the coefficient of variation of uGH was correlated with height standard deviation score (HtSDS, r = 0.38, P< 0.05), while the relative constancy of short-term change in uGH (coefficient of incremental change, DeltaINC) was inversely correlated with DeltaHt (r = - 0.44) and HVSDS (r = - 0.42, both P< 0.05) but not with HtSDS. DeltaINC was also inversely correlated with the average size of individual growth spurts derived from the height velocity curves (r = - 0.45, P< 0.05). Using time series analysis to identify rhythms in uGH excretion, a positive correlation was found between the magnitude of rhythms of a period of 2 to 4 weeks and HtSDS (r = 0.40, P< 0.05). These data demonstrate that variability in GH is a more important determinant of normal childhood growth rate than the amount of GH alone. Stature is correlated to the overall variability in GH release, while increment in height and the magnitude of individual growth spurts are influenced by the constancy of the GH profile. This would imply that once the GH dose has been replaced in GH deficiency, optimal growth could only be achieved by varying the pattern of GH administration.

Adolescent↗
PubMed1998

A mixture model for sucking patterns of breast-fed infants.

Previous studies of sucking patterns have mainly been on bottle-fed babies and have assumed that the babies' sucks occur within bursts separated by gaps of predetermined minimum length which is fixed over the feed. This study considers babies that are breast-fed, a more complex and natural process than bottle-feeding, and develops a more sophisticated model for the pattern of bursts and gaps which allows the parameters of the process to vary over the feed. We consider data from four breast feeds of each of 32 babies. We develop a two-component mixture model based on an underlying Markov chain model for the switching between bursts and gaps. We use the model to provide summary statistics for each feed and give estimates of the normal range of each of the model's parameters.

Breast Feeding↗
PubMed1998

Compliance in an anti-hypertension trial: a latent process model for binary longitudinal data.

We propose an alternative to the method of generalized estimating equations (GEE) for inference about binary longitudinal data. Unlike GEE, the method is practicable when the data consist of long time series on each subject and the set of observation times is not necessarily common to all subjects. Instead of modelling the intra-series correlations explicitly, we assume that a subject's propensity to respond is governed by an underlying, but unobserved, stationary continuous process. Given a realization of this process, we assume that the binary responses are conditionally independent, with the probability that a subject responds positively at any given time t depending on the value of the underlying process at that time and also on any covariates specific to the subject at that time. We develop an algorithm for estimating the parameters in this model, and investigate its effectiveness using simulation methods. We also apply the methodology to data collected in a trial investigating the effect of self-measurement of blood pressure on compliance in taking medication during a course of anti-hypertension treatment.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Seasonal variation of thermophilic campylobacters in lambs at slaughter.

A survey of the isolation rate and population size of thermophilic campylobacters in lambs at slaughter was carried out to determine the seasonal variation of thermophilic campylobacters in ovine hosts. Isolation rates determined by enrichment methods were always higher than those using direct plating onto selective agar and showed that Campylobacter could be isolated from 91.7% (n = 360) of samples from the small intestine of the lambs. Enumerations (MPN), done monthly over a 2-year period, averaged 4.00 log 10 (n = 1080, S.D. 0.16) campylobacters g-1 fresh weight (fw) intestinal contents with some samples giving values higher than 7 log MPN gfw-1. These results show that the prevalence of thermophilic campylobacters in sheep intended for slaughter is much higher than previously reported. Statistical analyses showed that there was a significant seasonal periodicity in the Campylobacter populations in the small intestines of lambs at slaughter (P = 0.004) but that there was no statistical relationship with environmental parameters such as minimum and maximum temperature, rainfall or hours of sunshine. In an analysis along the length of the intestinal tract of lambs, campylobacters were isolated from 80% of small intestine and 30% of rumen samples, but not from the true stomach, large intestine or caecal samples. A survey of sheep grazing on salt marsh, fell (upland) and farm pasture showed that the isolation rate of thermophilic campylobacters in fresh faeces was substantially lower (29.3% (n = 420)) than that from the small intestine of lambs at slaughter. No significant difference (> 0.05) was found between the isolation rate of campylobacters from faeces sampled in late spring/early summer and autumn, nor between the different types of grazing.

Abattoirs↗
PubMed1998

The seasonal variation of thermophilic campylobacters in beef cattle, dairy cattle and calves.

The epidemiology of clinical cases of campylobacter in temperate climates shows a striking seasonality. In the search for a seasonal environmental reservoir changes in the carriage rate and population size of campylobacters in bovine hosts with time have been measured. Most probable number (MPN) methodology was used to enumerate thermophilic campylobacters in samples taken from the small intestines of beef cattle at slaughter and the fresh faeces of four dairy herds and new-born calves. Statistical analyses revealed significant evidence for seasonal periodicity in the data from dairy herds (P = 0.044). Not only was there a departure from constancy within a 12-month interval but these data revealed a true seasonality, that is, the same periodicity in numbers from one year to the next. Each herd had two peaks per year, in approximately spring and autumn. Peaks coincided in herds on neighbouring farms but those on farms in the north preceded those on farms in the south by 2 and 1 months, respectively (P = 0.0057). Intestinal carriage by beef cattle at slaughter was 89.4% (n = 360) with an average MPN campylobacters per gram fresh weight (MPN gfw-1) of 6.1 x 10(2). Average MPN gfw-1 in faeces from the dairy herds and calves were 69.9 (S.D. 3) and 3.3 x 10(4) (S.D. 1.7 x 10(2)). There was no evidence of seasonal periodicity in the size of the campylobacter population in beef cattle at slaughter. Calves were campylobacter free at birth but became colonized with a few days.

Animals↗
PubMed1998

Nonparametric estimation of covariance structure in longitudinal data.

In longitudinal studies, the effect of various treatments over time is usually of prime interest. However, observations on the same subject are usually correlated and any analysis should account for the underlying covariance structure. A nonparametric estimate of the covariance structure is useful, either as a guide to the formulation of a parametric model or as the basis for formal inference without imposing parametric assumptions. The sample covariance matrix provides such an estimate when the data consist of a short sequence of measurements at a common set of time points on each of many subjects but is impractical when the data are severely unbalanced or when the sequences of measurements on individual subjects are long relative to the number of subjects. The variogram of residuals from a saturated model for the mean response has previously been suggested as a nonparametric estimator for covariance structure assuming stationarity. In this paper, we consider kernel weighted local linear regression smoothing of sample variogram ordinates and of squared residuals to provide a nonparametric estimator for the covariance structure without assuming stationarity. The value of the estimator as a diagnostic tool is demonstrated in two applications, one to a set of data concerning the blood pressure of newborn babies in an intensive care unit and the other to data on the time evolution of CD4 cell numbers in HIV seroconverters. The use of the estimator in more formal statistical inferences concerning the mean profiles requires further study.

Anti-HIV Agents↗
PubMed1995

Second-order analysis of space-time clustering.

We consider the problem of detecting and describing space-time interaction in point process data. We extend existing second-order methods for purely spatial point process data to the spatial-temporal setting. This extension allows us to estimate space-time interaction as a function of spatial and temporal separation, and provides a useful reinterpretation of a popular test, due to Knox, for space-time interaction. Applications to simulated and real data indicate the method's potential.

Cluster Analysis↗
PubMed1994

Semiparametric models for longitudinal data with application to CD4 cell numbers in HIV seroconverters.

The paper describes a semiparametric model for longitudinal data which is illustrated by its application to data on the time evolution of CD4 cell numbers in HIV seroconverters. The essential ingredients of the model are a parametric linear model for covariate adjustment, a nonparametric estimation of a smooth time trend, serial correlation between measurements on an individual subject, and random measurement error. A back-fitting algorithm is used in conjunction with a cross-validation prescription to fit the model. A notable feature in the application is that the onset of HIV infection is associated with a sudden drop in CD4 cells followed by a longer-term slower decay. The model is also used to estimate an individual's curve by combining his data with the population curve. Shrinkage toward the population mean trajectory is controlled in a natural way by the estimated covariance structure of the data.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Effects of the ovary, sucking stimulus and season on the pattern of LH and FSH release in the female tammar, Macropus eugenii.

The sequential effects of removal of the corpus luteum, removal of the non-luteal ovary and sucking stimulus and the effects of season of the year on the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) have been determined in the tammar wallaby, Macropus eugenii. Plasma concentrations of LH and FSH were measured at 15 min intervals for 6 h in eight animals at four successive times in the breeding season (lactational quiescence); (A) while they were intact and lactating, (B) 10 days after removal of the ovary bearing the quiescent corpus luteum, (C) 21 days after bilateral ovariectomy and (D) 21 days after removal of the sucking stimulus, and (E) in the following non-breeding season (seasonal quiescence). Single blood samples were taken twice weekly during lactational quiescence. In the presence of ovarian tissue, basal concentrations of LH were low (0.94 ng mL-1) with pulses of low magnitude (1.3 ng mL-1) and low frequency (1.4 pulses per 6 h). There was no response to luteectomy but all three parameters increased after bilateral ovariectomy. Removal of the sucking stimulus affected the LH pulse frequency but seasonal differences were not evident. The pattern of release of FSH was not pulsatile. There was no response to luteectomy in basal concentrations of FSH but these rose significantly after bilateral ovariectomy (P less than 0.001) in lactational quiescence. There was no effect of removing the sucking stimulus but in seasonal quiescence concentrations were higher. The results indicate that non-luteal ovarian tissue is essential for the negative-feedback effects on LH and FSH secretion, that the pattern of release of LH, but not FSH, is pulsatile, and that there is no marked seasonal change in hypothalamo-hypophysial activity.

Animals↗
PubMed1991

Spatial segregation between populations of ponto-cerebellar neurons: statistical analysis of multivariate spatial interactions.

This study applies terms and methods for describing spatial interactions between multivariate spatial point patterns, which are, to our knowledge, new in neurobiology. We consider two categories of points, type 1 and 2, distributed within a certain reference volume (such as a nucleus of the brainstem or a cortical area). The points may, for example, represent different categories of labelled cells or axonal fields of termination. We say that there is spatial neutrality between points of type 1 and 2 if the types are signed by random labelling. If a mechanism drives the two point categories together, we say that the point patterns are positively associated. Conversely, if a mechanism drives type 1 and 2 points apart, we say that they are segregated. By comparing two cumulative distribution functions of distances between points, we can distinguish neutrality, positive association, and segregation. One function, H12(t), is the cumulative distribution function of the distance t between a pair of randomly selected points of type 1 and 2. The other, H00(t), is the corresponding function for a pair of points randomly selected without reference to type. Plots of the estimated difference between these two functions give an indication of positive association, neutrality, or segregation. A statistical test, based on simulations of random (neutral) distributions, can be used to see whether deviations from neutrality are significant. We apply the analysis described above to a major pathway of the brain, namely the ponto-cerebellar projection. Different types of cells in the pontine nuclei are retrogradely labelled with the fluorescent tracers Rhodamine-B-isothiocyanate, Fluoro-Gold, and Fast Blue. The tracers are injected in adjacent or more distant folia of the cerebellar paraflocculus. The location of the somata of labelled cells are recorded and the total distribution reconstructed in three dimensions and displayed on a dynamic graphics workstation. We ask whether different units (folia) in the paraflocculus receive information from the same population, from two different positively associated populations, or from segregated cell populations. We find a statistically significant tendency for cell populations projecting to adjacent folia to be positively associated, although there are few cells containing multiple labels. Populations of neurons projecting to folia wider apart are significantly segregated. From inspections of the reconstructions, using real-time rotations, we find that the swarms of labelled neurons tend to accumulate in shells or lamellae in the pons. Within the lamellae, the cells are aggregated in clusters and bands with empty holes (containing unlabelled ponto-cerebellar cell bodies, presumably projecting to other cerebellar targets) in between.(ABSTRACT TRUNCATED AT 400 WORDS)

Amidines↗
PubMed1991

Second-order analysis of spatial clustering for inhomogeneous populations.

Motivated by recent interest in the possible spatial clustering of rare diseases, the paper develops an approach to the assessment of spatial clustering based on the second-moment properties of a labelled point process. The concept of no spatial clustering is identified with the hypothesis that in a realisation of a stationary spatial point process consisting of events of two qualitatively different types, the type 1 events are a random sample from the superposition of type 1 and type 2 events. A diagnostic plot for estimating the nature and physical scale of clustering effects is proposed. The availability of Monte Carlo tests of significance is noted. An application to published data on the spatial distribution of childhood leukaemia and lymphoma in North Humberside is described.

Biometry↗
PubMed1990

Statistical analysis of corticopontine neuron distribution in visual areas 17, 18, and 19 of the cat.

The spatial organization of visual corticopontine neurons was studied both at a "large scale" (in relation to cortical visual field maps) and at a "small scale" (in relation to cortical modular organization). Large injections of horse-radish peroxidase-wheat germ agglutinin were made in the pontine nuclei. In complete series of sections from parts of areas 17, 18, and 19, the position of each retrogradely labeled neuron was recorded with an x-y plotter connected to the microscope stage. Each cell was thus given a set of x, y, and z coordinates. After alignment of the sections, three-dimensional computer reconstructions of the distribution of the labeled cells were made. With program RPOP (developed by Blackstad and Bjaalie, '88), the reconstructions were studied with different rotations, scaling, etc. In addition, section-independent parts of reconstructions were isolated ("windows") and further analyzed. Curved parts were automatically unfolded for inspection of distribution patterns and determination of cell densities. The spatial distribution of the labeled cells was analyzed within small windows, where density gradients are negligible. We confirm and extend previous demonstrations of a large-scale aggregation of visual corticopontine cells due to density gradients by showing that densities of corticopontine neurons increase linearly as a function of distance from paracentral to lower visual field representations in area 17 (and partly in areas 18 and 19). We demonstrate that density gradients are steeper in area 17 than in area 18. For example, clear-cut differences between the areas in mediolateral density gradients are found. These findings are discussed in relation to the different visual field maps of the areas and the existence of a similar visual field representation in corticopontine projections from different visual areas. The type of small-scale distribution (randomness or non-randomness, aggregation into clusters, bands, etc.) was studied with statistical methods. Such analysis shows that the labeled cells within small zones are non-randomly distributed in all three areas. In most cases, the analysis indicates an aggregated spatial distribution. A possible relationship to the cortical map of direction selectivity is discussed. To our knowledge, this study is the first to combine the use of three-dimensional computer reconstructions of a population of labeled neurons, with subsequent statistical analysis of spatial point (cell distribution) patterns.

Animals↗
PubMed1990

Rapid pulses of luteinizing hormone during the ovarian cycle.

Luteinizing hormone has been shown to be secreted in a complex pattern of low-amplitude, high-frequency pulses superimposed on high-amplitude, low-frequency pulses. To test the hypothesis that the rapid, small pulses vary during the ovarian cycle, 16 normal women were studied on two occasions each, in the early and late follicular phases of one cycle or the luteal and following early follicular phase. Blood samples were taken every 1 min for 1 h. Statistical methods of time series analysis were applied to the data. There were significant amplitude differences between subjects at all stages of the cycle. We found no evidence to support the hypothesis that the frequency of the small rapid pulses varied during folliculogenesis. The results for the luteal phase, while less uniform, showed no consistent change. It is suggested that the rapid pulses may be related to function of the hypothalamic-pituitary axis rather than direct ovarian control.

Adolescent↗
PubMed1989

Statistical methods for monitoring the AIDS epidemic.

This article describes statistical methods for monitoring the epidemic of the acquired immunodeficiency syndrome (AIDS). A log-linear model is proposed to estimate AIDS incidence and its growth rate while taking account of delays in case reporting. An empirical Bayes approach for estimating the epidemic growth rate in low prevalence subgroups is introduced. These methods are illustrated with an analysis of AIDS incidence trends for seven risk groups in each of six geographic regions using the Centers for Disease Control AIDS case registry data as of September 1987. The analysis finds that AIDS incidence is currently doubling about once every two years and that the relative composition of new cases is shifting away from the older epidemics such as in north-eastern homosexual communities.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Luteinizing hormone in women is secreted in superimposed pulse patterns.

1. The pulsatile nature of luteinizing hormone (LH) secretion has recognized physiological and clinical importance, but because of the difficulties with statistical analysis of serial data the precise nature of this pulsed signal is poorly understood. Several groups have noted small-amplitude, high-frequency pulses superimposed on large slower pulses, but, using conventional methods of analysis, it is not possible to distinguish these from assay variation or to characterize them. 2. In an alternative approach we have applied the methods of time series analysis which identify the harmonic patterns within data. Twenty-four healthy women in the early follicular phase of the cycle had blood samples taken at intervals of 1, 5 or 10 min for up to 6 h. 3. We found that LH secretion consists of superimposed harmonics of varying amplitude which occur in frequency bands of about (a) 1-3 h and (b) 2-3 min. Investigations excluded a reproducible pulsatility in our LH assay, implying that the small fast pulses are physiological events. 4. We conclude that LH release is highly complex and that the methods of time series analysis permit identification and characterization of the multiple pulses.

Adult↗
PubMed1989

LH in polycystic ovary syndrome: reproducibility and pulsatile secretion.

Serum concentrations of LH are increased in polycystic ovary syndrome (PCOS). We have investigated two aspects of LH secretion which have not previously been reported: its reproducibility within individuals and the pattern of superimposed pulses of LH secretion. In nine patients with PCOS the mean concentration of LH was calculated from 24 blood samples taken at 15-min intervals for 6 h on two or three occasions over 1 year. Results showed differences in mean LH between subjects but reproducible concentrations within subjects over that period. It has been shown that LH is secreted in a complicated pattern of superimposed pulses which can be characterized by using the statistical methods of time-series analysis. To evaluate these pulse patterns of LH we studied nine patients with PCOS and compared the results with those of 12 normal women in the early follicular phase of the ovarian cycle. Blood samples were taken at either 5-min intervals for 6 h of 1-min intervals for 1 h. Pulses were detected in both groups at frequencies of about 1 h and 2 to 3 min. There was no significant difference in the pulse frequencies between the patients and controls but the amplitude of both groups of pulses was increased in the PCOS patients.

Adult↗