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R R Regal

Publications and source records attributed to R R Regal.

13 recordsLinked to original sources
PubMed1992

The value of capture-recapture methods even for apparent exhaustive surveys. The need for adjustment for source of ascertainment intersection in attempted complete prevalence studies.

Almost all reported prevalence studies of which we are aware make exhaustive attempts to find diagnosed individuals and report all affected individuals, but make no attempt to estimate or adjust for missing cases. Yet very simple methods introduced in the planning stage of a prevalence study may enable investigators, or at least those subsequently reading their reports, to derive such adjusted estimates. If investigators keep track of the nature of the ascertainment of cases by source and collect and report data that allow calculation of the number of cases by source intersection, then they, or at least others, may derive estimates of missing cases and of the total population affected, by using readily available analogues of capture-recapture methods developed for wildlife populations censuses. Unfortunately, such methods are often inappropriately disparaged or ignored by epidemiologists. The derived estimates are sensitive to assumptions about dependence or independence ("interaction") of various sources, assumptions that sometimes are unprovable, and these estimates have some uncertainty because of statistical fluctuation. Moreover, most investigators who attempt exhaustive prevalence studies apparently believe that they have ascertained all cases and that there is no need to attempt to adjust for, let alone provide data pertinent to, the number of missing cases or to use a statistical method that will at best imply a certain imprecision to their result. Yet a survey that reports prevalence data without adjustment for, or data on, source intersection in essence makes an estimate of missing cases--zero--while providing no quantitative grounds for that claim. The results of all such surveys should be regarded with skepticism because, at best (if the case reports are accurate), they provide only a lower boundary of prevalence. We illustrate the grounds for these views by analyzing data from an apparently exhaustive prevalence study that used at least 14 distinct sources for ascertainment, including advertising, to find cases. Available limited data on source intersection provided in the report enable the plausible inference that the study missed about 25-40% of cases. We urge that no attempted complete prevalence studies be presented without data on ascertainment by source intersection.

Bias↗
PubMed1992

Interrelationships of relative risks of birth defects in embryonic and fetal deaths, in livebirths, and in all conceptuses.

Most studies of associations with birth defects are undertaken in livebirths. An observed association in livebirths different from unity may be compatible with no association in conceptuses if "balanced" by a particular relative risk in embryonic and fetal deaths. We derived formulae to address the following queries: (1) If one observes in livebirths a relative risk of birth defect, tau def,lb, then, with what combinations of relative risk of defect in embryonic and fetal deaths, tau def,efd, and in all conceptuses, tau def, is this value compatible? (2) What balancing relative risk in embryonic and fetal deaths is predicted if there is no causal association in all conceptuses? (3) Under what circumstances is there no relative risk in embryonic and fetal deaths that can balance an observed relative risk in livebirths? We present an expression for tau def,efd in terms of five other variables: tau def,lb, tau def, and tau efd (the relative risk of embryonic or fetal death), and the lethalities of the average (unexposed) conceptus and of the (unexposed) defective conceptus. This equation enables one to derive the balancing relative risk in embryonic and fetal deaths, bal tau def,efd, which is the value of tau def,efd when tau def = 1.0. If bal tau def,efd is negative, no such balancing relative risk exists, and any observed association in livebirths is incompatible with a null association in all conceptuses, that is, the association cannot be explained completely by differential selection of conceptuses with defect.

Abortion, Spontaneous↗
PubMed1991

The effects of model selection on confidence intervals for the size of a closed population.

One encounters in the literature estimates of some rates of genetic and congenital disorders based on log-linear methods to model possible interactions among sources. Often the analyst chooses the simplest model consistent with the data for estimation of the size of a closed population and calculates confidence intervals on the assumption that this simple model is correct. However, despite an apparent excellent fit of the data to such a model, we note here that the resulting confidence intervals may well be misleading in that they can fail to provide an adequate coverage probability. We illustrate this with a simulation for a hypothetical population based on data reported in the literature from three sources. The simulated nominal 95 per cent confidence intervals contained the modelled population size only 30 per cent of the time. Only if external considerations justify the assumption of plausible interactions of sources would use of the simpler model's interval be justified.

Confidence Intervals↗
PubMed1991

Conceptus viability, malformation, and suspect mutagens or teratogens in humans. The Yule-Simpson paradox and implications for inferences of causality in studies of mutagenicity or teratogenicity limited to human livebirths.

If a genetic disorder or a congenital malformation is associated with embryonic or fetal death, then this may distort reported associations of environmental or biological factors with genetic and congenital disorders. We illustrate how such distortion may occur in humans as a manifestation of the Yule-Simpson (or Simpson) statistical paradox. We analyze the reported negative association of maternal smoking and Down syndrome in livebirths and demonstrate that under plausible conditions, valid negative associations both in livebirths and in embryonic or fetal deaths can occur, despite the fact that in all conceptuses there may be no association whatsoever. A similar analogous manifestation of the Yule-Simpson paradox may hold for positive associations. That is, positive relative risks may occur for an alleged mutagen or teratogen in separate studies both of livebirths, and of embryonic and fetal deaths, despite the absence of any effect in all conceptuses. These considerations illustrate the need for data on genetic disorders and malformations in embryonic and fetal deaths, and the need for a synthesis of such data with those from studies in livebirths before valid inferences may be made about mutagenic or teratogenic effects of environmental or biological factors.

Congenital Abnormalities↗
PubMed1988

Relation of blood flow to VO2, PO2, and PCO2 in dog gastrocnemius muscle.

We pump-perfused gastrocnemius-plantaris muscle preparations at constant pressure to study the relationship of muscle blood flow (Q) to muscle oxygen consumption (VO2), venous oxygen tension (PVO2), and venous carbon dioxide tension (PVCO2) during steady-state exercise at different rates. Tests were performed under four experimental conditions produced by altering the perfusate blood-gas status with a membrane lung. The consistency of the relationship of Q to other variables was evaluated by statistical analysis of fitted curves. Not one of the above listed variables had the same relationship with Q in all four of the experimental conditions we tested. However, we did find that a consistent relationship existed among Q, PVO2, and PVCO2 in our data. That relationship is well described by the equation (Q-23).[PVO2 - (0.5.PVCO2) - 3] = 105 (when Q is expressed in ml.100 g-1.min-1 and PVO2 and PVCO2 in mmHg). One interpretation of this result is that both PO2 and PCO2 are important variables in the control of blood flow in skeletal muscle the combined influence of which could account for nearly all of the hyperemia response to steady-state muscle exercise.

Animals↗
PubMed1984

The frequency of 47,+21,47,+18, and 47,+13 at the uppermost extremes of maternal ages: results on 56,094 fetuses studied prenatally and comparisons with data on livebirths.

We examined the proportions (or so called "rates") of fetuses with 47,+21, 47,+18, or 47,+13 diagnosed prenatally in women at the upper extremes of age. Our analysis was prompted by results from a large scale European study of amniocentesis which indicated that after increasing exponentially from age 35 years, the proportions of the autosomal trisomies reached a peak at a specific age and then leveled off or declined at the upper end of the age range. We analyzed North American data on 56,075 fetuses studied because of no known cytogenetic risk factor (aside from maternal age). This is the largest series to date. For 47,+21, the data from amniocentesis studies provide no evidence for any drop in the rate of change of proportion with maternal age up to 49 years. There is, if anything, a trend in our data to a steepening in the exponential rate of change at the upper extreme of age (above 46 years). Data from livebirths on the Down syndrome phenotype are at least consistent with an exponential rate of increase in proportion affected up to age 49 years. For 47,+18 our data from prenatal diagnoses are more consistent with an exponential increase up to age 43 years and a level proportion (or "rate") after that. For 47,+13 no cases were observed above age 42 years, consistent with the drop in proportion affected above this age observed in the European series. We emphasize the possible effect of sampling fluctuation and reporting error upon these apparent trends.

Chromosome Aberrations↗
PubMed1984

A search for a paternal-age effect upon cases of 47, +21 in which the extra chromosome is of paternal origin.

If there is a paternal-age effect for 47, +21, it would appear most likely to be present primarily, if not exclusively, in cases in which the extra chromosome is of paternal origin. To search for such an effect, data were reviewed from seven series reporting at least four cases of 47, +21 of paternal origin. The mean of the paternal age-maternal-age difference of such cases (dp) in each series was compared with the mean of the paternal-age differences of cases in the same series that were of maternal origin (dm). If the difference between these (dp - dm or delta) is greater than zero, then this would imply a positive paternal-age effect among cases of paternal origin, at least compared to those of maternal origin. In the seven series, the values of delta ranged from -2.2 years to +3.4 years, and there was no evidence in these comparisons for any consistent trend. A second analysis controlled for any effect of maternal-age variation upon this difference. Each case of paternal origin was matched with a case of maternal origin in the same series that was of the same maternal age. Of 60 cases of paternal origin, exact matches were found for 38. In these 38, the mean value of the difference in parental ages, dp - dm or delta, was negative, about -1.1 (+/- 5.1 years). The difference was highest for the nine cases of paternal origin in which the extra chromosome resulted from presumptive second-division non-disjunction, -1.8 (+/- 3.8 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Paternal age and Down syndrome in British Columbia.

Among Down syndrome cases born in 1964--1976 reported to the British Columbia Registry for Handicapped Children, the mean parental age was about half a year greater than in the entire population of live births after controlling for maternal age, a difference significant at the .05 level. After adjustment for maternal age, a regression analysis was consistent with an increase of 1.024-fold for each year of paternal age. Among Down syndrome cases in 1952--1963, however, for which ascertainment appears likely to be less complete, there was no evidence for a significant paternal age effect. The reasons for the variation between the two groups investigated here and the heterogeneity in results among studies of other populations are discussed.

British Columbia↗
PubMed1980

A search for evidence for a paternal age effect independent of a maternal age effect in birth certificate reports of Down's syndrome in New York state.

The discovery that in 20% to 30% of Down's syndrome cases the extra chromosome is of paternal origin, and the recent independent report of two groups that maternal age-specific rates are two-fold greater for livebirths to couples in which the father is aged 55 years and over prompted this investigation. Analyses were of coded birth certificate reports of Down's syndrome in Upstate New York residents in the years 1963-1974. The expected numbers of cases, on the assumption of no paternal age effect, were determined at each paternal age interval (and at each paternal age minus maternal age interval) adjusting for an effect of maternal age; these were compared with observed values. There was a slightly lower number of observed than expected cases for fathers aged 55 years and over (ratio = 0.76), and the results exclude with 95% confidence an increase of 1.5-fold or greater in rates in this group after correction for maternal age. There was, moreover, no overall evidence for any trend to increasing rates with paternal age. Regression analyses in which the data were first fit to functions of maternal age and subsequently terms involving paternal age were introduced also revealed no evidence that paternal age made a significant independent contribution to the observed rates in contrast to the conclusion of earlier positive reports.

Adolescent↗
PubMedDate not supplied

Goodness-of-fit based confidence intervals for estimates of the size of a closed population.

Methods for estimating the size of a closed population often consist of fitting some model (e.g. a log-linear model) to data with a missing cell corresponding to the members of the population missed by all reporting sources. Although the use of the asymptotic standard error is the usual method for forming confidence intervals for the population total, the sample sizes are not always large enough to produce valid confidence intervals. We propose a method for forming confidence intervals based upon changes in a goodness-of-fit statistic associated with changes in trial values of the population total.

Epidemiologic Methods↗