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Biomedical subjects

A J Scott

Publications and source records attributed to A J Scott.

At least 19 recordsLinked to original sources

A simple method for analysing overdispersion in clustered Poisson data.

A simple method is proposed for analysing grouped count data exhibiting overdispersion relative to a Poisson model. The method is similar to the approach suggested for the analysis of clustered binary data in Rao and Scott (1992). It requires no specific model for the overdispersion and it can be implemented easily using standard programs designed to handle independent Poisson counts, after a small amount of preprocessing.

Animals

Aqueous solubilization of transmembrane peptide sequences with retention of membrane insertion and function.

We recently reported that the peptide C-K4-M2GlyR mimics the action of chloride channels when incorporated into the apical membrane of cultured renal epithelial monolayers. C-K4-M2GlyR is one of a series of peptides that were prepared by the addition of lysine residues to the N- or C-terminus of the M2 transmembrane sequence of the brain glycine receptor. This study addresses how such modifications affect physical properties such as aqueous solubility, aggregation, and secondary structure, as well as the ability of the modified peptides to form channels in epithelial monolayers. A graded improvement in solubility with a concomitant decrease in aggregation in aqueous media was observed for the M2GlyR transmembrane sequences. Increases in short-circuit current (I(SC)) of epithelial monolayers were observed after treatment with some but not all of the peptides. The bioactivity was higher for the more soluble, less aggregated M2GlyR peptides. As described in our previous communication, sensitivity of channel activity to diphenylamine-2-carboxylate, a chloride channel blocker, and bumetanide, an inhibitor of the Na/K/2Cl cotransporter, was used to assess changes in chloride selectivity for the different assembled channel-forming peptides. The unmodified M2GlyR sequence and the modified peptides with less positive charge are more sensitive to these agents than are the more highly charged forms. This study shows that relatively insoluble transmembrane sequences can be modified such that they are easier to purify and deliver in the absence of organic solvents with retention of membrane association, insertion, and assembly.

Amino Acid Sequence

The impact of influenza and influenza-like illness on productivity and healthcare resource utilization in a working population.

Four hundred and eleven subjects who either reported to Occupational Health at onset of influenza or influenza-like illness (I/ILI) symptoms or on return to work completed questionnaires on entry to the study and after 28 days. On average they were incapacitated or confined to bed for 2.4 days, missing 2.8 days from work per episode of illness. On return to work, they reported reduced effectiveness and inability to resume normal activity until a mean 3.5 days after the onset of symptoms. Each participant reported a mean of 6.5 I/ILI symptoms. There was a positive correlation between the number of symptoms and bed days (r = 0.24) and missed work days (r = 0.18). There was a positive correlation between the number of healthcare contact and the number of reported symptoms (r = 0.23). A relatively high level of contact with general practitioners and pharmacists was observed and there was substantial use of both prescription and over-the-counter medication. In conclusion, the impact of I/ILI on productivity in a working population and the resultant cost to employers and employees may be considerable.

Adult

Re-using data from case-control studies.

Despite its ability to maximize statistical power while keeping data collection costs to a minimum, case-control sampling provides a non-representative sample of the population. When fitting a logistic regression model to data obtained in such a study, using the variable stratifying the population as the response, it is well known that the estimate of the constant term will be biased, but those of the coefficients of the covariates will not. However, subsequent to the case-control study, it is often desired to conduct a secondary analysis, using a variable that was previously a covariate in the main study as the response. If this new response is associated with the original variable used to stratify the population into cases and controls, a conventional logistic regression analysis will usually result in biased estimates of all the regression coefficients, not just the constant. This situation has recently been studied by Nagelkerke et al. who describe some situations where no bias occurs. In this paper we discuss how to calculate maximum likelihood estimates of all the regression coefficients, in the situation where the sampling rates for cases and controls are known. An example using data from the New Zealand Cot Death Study is presented.

Case-Control Studies

Suppression of an inhibitory jaw reflex by the anticipation of pain in man.

Electromyographic recordings (EMGs) were made from the active masseter muscle, of the inhibitory reflex evoked by application of electrical stimuli to the skin of the upper lip in 15 human subjects. In control sequences, the reflex had a mean latency and duration (+/- S.E.M.) of 45.4 +/- 1.3 msec and 47.9 +/- 2.8 msec, respectively. Significant decreases in the reflex as well as increases in heart rate and anxiety levels assessed by a visual analogue scale, occurred when the subjects were stressed by the anticipation of receiving painful electrical stimuli above the ankle (P < 0.00005; Student's t-tests). During such sequences, the magnitude of the reflex measured by integration of the EMG, was reduced by 47.7 +/- 5.6%. This effect involved a reduction in both the duration and depth of the inhibitory wave. It occurred regardless of whether the painful stimuli were applied during or after the recording of the reflex and of whether the baseline activity in the muscle was inadvertently raised or lowered during the stressful sequences. It is concluded that stress induced by the anticipation of pain, can markedly reduce an inhibitory jaw reflex in man by exerting an influence on the reflex pathway prior to the motoneurones.

Adult

A comparison of methods for correlated ordinal measures with ophthalmic applications.

For many clinical trials and epidemiologic investigations in the field of ophthalmology, paired ordinal data are often collected through the detailed grading of retinal photographs. One method for analysis of these data is the extension of the generalized estimating equation (GEE) methodology to multinomial data with cumulative link functions. Prior to the development of this advanced technique, however, ophthalmologists developed a method of combining the ordinal responses of both eyes of a patient into a single person-level response on a new ordinal scale. A relationship between the regression coefficients of these two methods is derived as a function of the correlation between eyes. We investigate the applicability of this result and the relationship of the standard errors in simulation experiments and in an example from the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

Diabetic Retinopathy

Tests for trend in developmental toxicity experiments with correlated binary data.

In this article, the operating characteristics of recently proposed tests for trend in correlated binary data arising in laboratory studies of developmental toxicity are examined using both computer-generated and experimental data. Specifically, we consider adjusted Cochran-Armitge tests based on the Rao-Scott transformation which are of the same general form as that for uncorrelated data. In addition, generalized score tests based on generalized estimating equations allowing for extrabinomial variation in the data are discussed. Specific forms of these statistics demonstrating favorable type I and type II error rates are identified and recommended for use in practice. The application of these tests is illustrated using data from studies of developmental toxicity that have been reported in the literature.

Abnormalities, Drug-Induced

Relationships amongst some bacterial and yeast lactate and mandelate dehydrogenases.

Five yeast strains were isolated by enrichment culture on the basis of their ability to grow on mandelate and two of these strains were identified as Rhodotorula glutinis. In addition, a range of yeasts from culture collections was screened for growth on mandelate. The results suggest that mandelate utilization is a widespread but not universal characteristic within the genus Rhodotorula. Several of the yeasts contained an inducible NAD-dependent D(-)-mandelate dehydrogenase and an inducible dye-linked (presumably flavoprotein) L(+)-mandelate dehydrogenase. All the D(-)-mandelate dehydrogenases from the yeasts showed immunological cross-reactivity with each other (as judged by both immunoinhibition and immunoblotting), as did all the yeast L(+)-mandelate dehydrogenases that were tested. Determination of N-terminal amino acid sequences of several bacterial and yeast lactate and mandelate dehydrogenases, together with the evidence from the immunological studies, confirmed and extended previous proposals that there are several major groups of such dehydrogenases: FMN-dependent, membrane-bound L(+)-lactate and L(+)-mandelate dehydrogenases (M(r) = approx. 44,000) in bacteria, mitochondrial flavocytochrome b2 L(+)-lactate and L(+)-mandelate dehydrogenases (M(r) = approx. 59,000) in yeasts, FAD-dependent, membrane-bound D(-)-lactate and D(-)-mandelate dehydrogenases in bacteria, and soluble NAD-dependent D(-)-mandelate dehydrogenases in both bacteria and yeasts.

Alcohol Oxidoreductases

Microalbuminuria in a middle-aged workforce. Effect of hyperglycemia and ethnicity.

OBJECTIVE: To determine the prevalence of microalbuminuria in a mixed, ethnic population and to find the extent that ethnic variation in microalbuminuria can be explained by abnormal glucose metabolism, obesity, hypertension, hypertriglyceridemia, and life-style factors. RESEARCH DESIGN AND METHODS: Urinary albumin concentrations were measured in 5467 middle-aged Maori, Pacific Islander, and European workers who participated in a health-screening survey of 46 New Zealand companies. Participants provided a first-voided, morning urine sample; had a 75-g oral glucose tolerance test; had weight, height, and blood pressure measured; and completed a self-administered questionnaire about past medical history and sociodemographic status. RESULTS: A significantly higher prevalence of microalbuminuria was found in individuals with new cases of diabetes mellitus (24.1%), in cases of diabetes mellitus previously diagnosed (20.6%), and in those with impaired glucose tolerance (16.1%) compared with nondiabetic individuals (4.0%). Moreover, in the general population, a piecewise linear relationship was detected between albuminuria and plasma glucose with significant changes of slope corresponding with 2 h plasma glucose concentrations (95% confidence interval) of 6.7 (6.4-7.0) and 9.2 (8.6-9.8) mM, respectively. After adjusting for sex, obesity, hypertension, hypertriglyceridemia, cigarette smoking, and heavy alcohol consumption in a multivariate model, glycemia was the most significant determinant of urinary albumin concentrations in all three ethnic groups. However, blood glucose concentrations did not completely explain the higher relative risk (95% confidence interval) of microalbuminuria in Maori (5.97; 4.48-7.78) and Pacific Islander (5.33; 4.13-6.87) workers compared with European workers. CONCLUSIONS: Of the variables investigated, hyperglycemia was the most important factor explaining the high prevalence of microalbuminuria in Maori and Pacific Islander workers compared with the European workers. However, only 14.9% of the variation in urinary albumin concentrations was found in our multivariate model, and we have speculated on the contribution of other factors such as diet and coexisting renal diseases.

Adult

Asymptomatic bacteriuria in a multiracial workforce.

Prevalence of asymptomatic bacteriuria was determined in the first morning urine specimens from 5669 people who participated in a health screening survey of a local workforce. Higher age-standardized prevalences were observed in Maori women (18.0%), compared with Pacific Island women (9.8%) and European women (8.7%). Similarly, higher prevalences were observed in Maori men (3.2%), compared with Pacific Island men (0.7%) and European men (1.3%). After controlling for age and gender, the relative risk for asymptomatic bacteriuria in Maori people was estimated to be 2.22 times that for non-Maori people (associated 95% CI: 1.54-3.18). Significant associations of bacteriuria included a past history of myocardial infarction, a past history of kidney disease, absence of tertiary education, and impaired glucose tolerance. The most common pathogens, isolated from a subsample of 1660 participants, were Escherichia coli, 27 cases (50.9%), and Streptococcal sp, 14 cases (26.4%).

Adult

Albuminuria in people at least 40 years old: effect of alcohol consumption, regular exercise, and cigarette smoking.

We investigated the relation between albuminuria and life-style factors in 5670 people, ages 40 years and over, who participated in a health screening survey of a local workforce. The degree of albuminuria showed piecewise log-linear relationships with alcohol consumption and cigarette smoking, with changes in slope (and 95% confidence interval) corresponding with 5 (2, 8) g of alcohol/day and 10 (6, 14) cigarettes/day. After adjusting for age, gender, ethnicity, and other life-style variables, relative risks (95% confidence interval) of slight albuminuria for people consuming > 32 g of alcohol/day compared with nondrinkers, and for cigarette smokers compared with nonsmokers, were 1.74 (1.02, 2.98) and 1.37 (1.01, 1.88), respectively. However, there was no significant effect of exercise. We conclude that slight albuminuria is significantly associated with cigarette smoking and heavy alcohol consumption, consistent with its role as an index of risk of cardiovascular disease.

Adult

Dietary nutrient intakes and slight albuminuria in people at least 40 years old.

We studied the relation between diet and slight albuminuria in 5416 people, ages 40 years and over, who participated in a health screening survey of a local workforce. Degree of albuminuria showed log-linear univariate relations with dietary protein, cholesterol, and sodium intakes, and negative log-linear univariate relations with dietary fiber and polyunsaturated to saturated fat (P/S) ratio. After adjusting for age, gender, and ethnicity, the relative risk (95% confidence interval) for slight albuminuria was significantly increased in people reporting dietary cholesterol consumption > 226 mg/day compared with people reporting consumption < or = 226 mg/day [1.32 (1.02, 1.70)], and significantly reduced in people reporting dietary fiber consumption > 26 g/day compared with people reporting consumption < or = 26 g/day [0.74 (0.58, 0.95)]. There was no significant effect of dietary protein, P/S ratio, or salt intake. We conclude that risk of slight albuminuria is increased by consumption of dietary cholesterol and reduced by consumption of dietary fiber.

Adult

A simple method for the analysis of clustered binary data.

A simple method for comparing independent groups of clustered binary data with group-specific covariates is proposed. It is based on the concepts of design effect and effective sample size widely used in sample surveys, and assumes no specific models for the intracluster correlations. It can be implemented using any standard computer program for the analysis of independent binary data after a small amount of preprocessing. The method is applied to a variety of problems involving clustered binary data: testing homogeneity of proportions, estimating dose-response models and testing for trend in proportions, and performing the Mantel-Haenszel chi-squared test for independence in a series of 2 x 2 tables and estimating the common odds ratio and its variance. Illustrative applications of the method are also presented.

Animals

Health proposals and NZMA.

NZMA welcomes the opportunity for public debate over the degree to which the community should fund health care for all. It views the attempts to improve the integration of the health service with interest and hopes to enter a vigorous debate with government to ensure that the detailed proposals yet to be formulated will achieve the purpose we both desire. But the association is disappointed to see policies promoted that are often so reliant upon anecdote and a naive theory of economics. It is disappointing to see health policy altered so radically with so little analysis of facts. Waiting lists, as an example, are analysed with no statement of what proportion of hospital admissions are represented by waiting list patients. Part charges have been introduced in areas where there is no experimental justification for supposing that they will usefully alter patient behaviour. A more sophisticated approach is required. Some change must be sought in the so-called nonnegotiable part of the proposals.

Delivery of Health Care

Breast cancer diagnosis by screening mammography: early results of the Central Sydney Area Health Service Breast X-ray Programme.

The Central Sydney Area Health Service (CSAHS) Breast X-ray Programme is a pilot mammography screening project for breast cancer detection funded by the NSW Government. Screening by two-view mammography is carried out in a mobile van and is offered free to women aged over 45 years living in the CSAHS region, the inner western suburbs of Sydney. In the first 18 months of operation from March 1988, 7193 women were screened: 99 women underwent excision biopsy and 53 cancers were diagnosed. This is an overall detection rate of seven cancers per thousand women screened. Sixty per cent of the cancers were impalpable to the examining surgeon; 19% of all cancers were shown to have axillary node metastasis at the time of diagnosis. These results compare well with those of the major European screening studies.

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