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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
PubMed2005

Clustering of equine grass sickness cases in the United Kingdom: a study considering the effect of position-dependent reporting on the space-time K-function.

Equine grass sickness (EGS) is a largely fatal, pasture-associated dysautonomia. Although the aetiology of this disease is unknown, there is increasing evidence that Clostridium botulinum type C plays an important role in this condition. The disease is widespread in the United Kingdom, with the highest incidence believed to occur in Scotland. EGS also shows strong seasonal variation (most cases are reported between April and July). Data from histologically confirmed cases of EGS from England and Wales in 1999 and 2000 were collected from UK veterinary diagnostic centres. The data did not represent a complete census of cases, and the proportion of all cases reported to the centres would have varied in space and, independently, in time. We consider the variable reporting of this condition and the appropriateness of the space-time K-function when exploring the spatial-temporal properties of a 'thinned' point process. We conclude that such position-dependent under-reporting of EGS does not invalidate the Monte Carlo test for space-time interaction, and find strong evidence for space time clustering of EGS cases (P < 0.001). This may be attributed to contagious or other spatially and temporally localized processes such as local climate and/or pasture management practices.

Animals↗
PubMed2004

Frequency and spatial distribution of environmental Campylobacter spp.

Humans are exposed to Campylobacter spp. in a range of sources via both food and environmental pathways. For this study, we explored the frequency and distribution of thermophilic Campylobacter spp. in a 10- by 10-km square rural area of Cheshire, United Kingdom. The area contains approximately 70, mainly dairy, farms and is used extensively for outdoor recreational activities. Campylobacter spp. were isolated from a range of environmental samples by use of a systematic sampling grid. Livestock (mainly cattle) and wildlife feces and environmental water and soil samples were cultured, and isolates were presumptively identified by standard techniques. These isolates were further characterized by PCR. Campylobacter jejuni was the most prevalent species in all animal samples, ranging from 11% in samples from nonavian wildlife to 36% in cattle feces, and was isolated from 15% of water samples. Campylobacter coli was commonly found in water (17%) and sheep (21%) samples, but rarely in other samples. Campylobacter lari was recovered from all sample types, with the exception of sheep feces, and was found in moderate numbers in birds (7%) and water (5%). Campylobacter hyointestinalis was only recovered from cattle (7%) and birds (1%). The spatial distribution and determinants of C. jejuni in cattle feces were examined by the use of model-based spatial statistics. The distribution was consistent with very localized within-farm or within-field transmission and showed little evidence of any larger-scale spatial dependence. We concluded that there is a potentially high risk of human exposure to Campylobacter spp., particularly C. jejuni, in the environment of our study area. The prevalence and likely risk posed by C. jejuni-positive cattle feces in the environment diminished as the fecal material aged. After we took into account the age of the fecal material, the absence or presence of rain, and the presence of bird feces, there was evidence of significant variation in the prevalence of C. jejuni-positive cattle feces between grazing fields but no evidence of spatial clustering beyond this resolution. The spatial pattern of C. jejuni is therefore consistent with that for an organism that is ubiquitous in areas contaminated with cattle feces, with a short-scale variation in infection intensity that cannot be explained solely by variations in the age of the fecal material. The observed pattern is not consistent with large-scale transmission attributable to watercourses, wildlife territories, or other geographical features that transcend field and farm boundaries.

Animals↗
PubMed2004

Genotypic and antibiotic susceptibility characteristics of a Campylobacter coli population isolated from dairy farmland in the United Kingdom.

Campylobacter infections are the most common cause of bacterial enteritis in humans, and nearly 8% of such infections are caused by Campylobacter coli. Most studies have concentrated on Campylobacter jejuni, frequently isolated from intensively farmed poultry and livestock production units, and few studies have examined the spread and relatedness of Campylobacter across a range of geographical and host boundaries. Systematic sampling of a 100-km2 area of mixed farmland in northwest England yielded 88 isolates of C. coli from a range of sample types and locations, and water was heavily represented. Screening for antibiotic resistance revealed a very low prevalence of resistance, while genotyping performed by using three methods (flaA PCR restriction fragment length polymorphism [RFLP], pulsed-field gel electrophoresis [PFGE], and fluorescent amplified fragment length polymorphism [fAFLP]) provided insights into the genomic relatedness of isolates from different locations and hosts. Isolates were classified into 23 flaA groups, 34 PFGE groups, and five major fAFLP clusters. PFGE banding analysis revealed a high level of variability and no clustering by sample type. fAFLP and flaA analyses successfully grouped the isolates by sample type. We report preliminary findings suggesting that there is a strain of C. coli which may have become adapted to survival or persistence in water and that there is a group of mainly water-derived isolates from which unusual flaA PCR fragments were recovered.

Agriculture↗
PubMed2001

Investigation of spatial clustering from individually matched case-control studies.

The paper demonstrates how existing theory to assess spatial clustering based on second-moment properties of a labelled point process can be adapted to matched case-control studies. The null hypothesis that cases are a random sample from the superposition of cases and controls is replaced by the hypothesis that each case is a random sample from the set consisting of itself and its k matched controls. We compare the proposed test with other tests of spatial clustering, and describe an application to data on childhood diabetes in Yorkshire, England.

Journal Article↗
PubMed2000

Point-source modelling using matched case-control data.

We describe an extension to matched case-control studies of the parametric modelling framework developed by Diggle (1990) and Diggle and Rowlingson (1994) to investigate raised risk around putative sources of environmental pollution. We use a conditional likelihood approach for the family of risk functions considered in Diggle and Rowlingson (1994). We show that the likelihood surface that results from these models may be highly irregular, and provide a Bayesian analysis in which we investigate the posterior distribution using Markov chain Monte Carlo. An analysis of one-one matched data that were collected to investigate the relationship between respiratory disease and distance to roads in East London is presented.

Journal Article↗
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↗
PubMed1997

Seasonality of thermophilic Campylobacter populations in chickens.

The small intestines and caeca of chickens were monitored for seasonal variation of thermophilic campylobacters over a 12-month period. There was a significant seasonal fluctuation in the carriage rate which correlated with the following environmental parameters: sunshine hours (P = 0.0003) and minimum (P = 0.007) and maximum temperatures (P = 0.003). The number of campylobacters in the small intestine and caeca also showed significant seasonal variation (P = 0.0008); however, the periodicity in the caeca was significantly different from that in the small intestine (P = 0.007). The numbers of Campylobacter in the caeca were significantly higher than those in the small intestine (P = 0.001). No significant correlation was found between the numbers of campylobacters in the caeca and small intestines and the environmental parameters monitored.

Animals↗
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↗