Evaluation of Down's syndrome screening population data sets by simulation: analyser-specific parameters may be superior to meta-analysis-derived parameters.

OBJECTIVE: Choice of parameter sets used to calculate Down's syndrome risks is complicated. Published population statistics were compared with assay-specific parameters to optimise screening efficiency. DESIGN: Weight-corrected Gaussian population statistics for alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE(3)), expressed as log(10) multiples of median (MoM) were established for a Belgian cohort of 748 unaffected pregnancies. Using Cuckle's method and Access-specific data, Down's syndrome parameters were tailored to the Belgian cohort. Correlated marker triplets for affected and unaffected pregnancies were modelled and combined with maternal age to calculate term risks for Trisomy 21. Receiver-Operator-Curve (ROC) analysis was performed to identify the optimally-performing population set. RESULTS: Log-normal distributions for the Access markers had geometric mean MoM values close to zero and standard deviation values equal to 0.1460 (AFP), 0.2185 (HCG) and 0.1317 (uE(3)). Correlation between AFP and other markers was significant (p < 0.001). Correlation between HCG and uE(3) was not significant (p = 0.4818). The median ratio between the lowest and highest risk outcomes for the test MoM set was 4.3. Areas under ROC curves differed significantly (p < 0.001) between the models and the analyser-assay specific parameters resulted in the largest area. At a 1 in 250 threshold, sensitivity and specificity were 69% and 96%. At false-positive rates (1-specificity) = 5%, sensitivity was 72.5%. CONCLUSION: Population parameters significantly affect risk outcome and hence screening performance. Highest efficiency may be obtained with parameters tailored to an assay-specific population model. Consequently models from literature, without knowledge of the assay/analyser combination may lead to suboptimal performance.

Medians for second-trimester maternal serum markers: geographical differences and variation caused by median multiples-of-median equations.

OBJECTIVES: To establish gestational age-specific mid-trimester normal medians for the prenatal serum markers alpha fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3) for a Belgian population by using the Beckman Coulter Access chemiluminiscent immunoassays; to compare these data with data obtained from other geographical regions; to propose regression coefficients for regressed medians and analyse variation induced by different regression equations; to evaluate the effect of formulas used for gestation correction on estimating risk in Down's syndrome. DESIGN: Data derived from 862 fresh serum samples from women being screened for Down's syndrome pregnancy, composed of selected pregnancies deemed to be normal, were examined in a retrospective study. Regressed medians were calculated by using a first-degree logarithmic-linear fit of the raw data. Multiples-of-median (MoM) values estimated by using a simple logarithmic-linear equation were compared with those calculated with higher-degree polynomials chosen with a goodness-of-fit analysis. Model-specific variation was estimated and the effect on risk for Down's syndrome was evaluated. RESULTS: Regressed medians (Y) for Access serum markers AFP (IU/ml), HCG (IU/ml) and uE3 (nmol/l) for a Belgian population can be estimated with the equation Y = 10((A+BX)) with X = decimal weeks. The best fit was obtained with a third-degree and a second-degree polynomial for AFP and uE3, respectively. Differences between the medians and among the slopes of the geographical populations were found to be significant (analysis of covariance, p<0.001). CONCLUSIONS: Belgian marker medians versus gestational time are found to show a pattern that is similar to that in the literature. The log-linear equation is observed to give a good fit and can be suggested as a tool for calculating median MoM values for Belgian laboratories that use Access biochemical prenatal markers.

Weight correction of MoM values: which method?

BACKGROUND: Adjusting maternal serum markers for maternal weight is considered to be a standard practice when screening for pregnancies associated with Down's syndrome. The choice of model for taking maternal weight into account is, however, rarely explicitly evaluated. METHOD: The relationship between the maternal serum markers alphafetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3), determined with the Beckman Coulter access reagents and maternal weight was investigated in a cohort of 752 Belgian women being screened for pregnancy associated with Down's syndrome. Two different models (the log-linear equation and the linear-reciprocal equation) were used to determine the relationship between the serum markers and maternal weight. RESULTS: A significant relationship between log(10) multiples of median (MoM) values and weight (kg) was obtained for all markers, and the log-linear model had higher coefficients of determination (r(2)) when compared with the linear-reciprocal model. Weight correction with either method achieved the optimum effect that the correction factor for a woman with a population median weight of 65.5 kg was not significantly different from 1. Simulated weight-corrected MoM values with the two approaches were compared and variation was estimated. The mean difference between the weight-corrected MoM values calculated by the two methods was 7.8% (SD 4.3%) for AFP, 14.0% (4.4%) for HCG and 5.9% (3.2%) for uE3. This resulted in a difference in risk estimate of 1.66-5.34% for Down's syndrome owing to weight correction algorithm differences in women of median weight. CONCLUSION: The log-linear weight correction approach was shown to be marginally more effective by a goodness-of-fit analysis. Differences in weight-corrected MoM values estimated with the two approaches are highly significant (p<0.0001, Wilcoxon's paired sample test), but the effect on risk calculation was not significant. It was observed that the changes in risk became significant the more the MoM correction factors deviated from 1.

Studies of the life-history and energetics of marine and brackish-water nematodes : I. Demography of Monhystera disjuncta at different temperature and feeding conditions.

Aspects of the demography of Monhystera disjuncta were investigated at different temperatures (in agnotobiotic cultures) and in different feeding conditions (monoxenic cultures with different bacterial strains, and different densities in the feeding suspension with one strain). Embryonic development time, minimum generation time, egg deposition rate and adult longevity depend on temperature, quality and quantity of food offered. Body mass at maturity is an allometric function of food density. It is shown that a previously inferred selectivity in food uptake is an artifact of culture conditions. pH buffering and addition of sterols permit culture of the species on a wide variety of bacterial strains. M. disjuncta is less well adapted to take advantage of high food density than are nematodes from polysaprobic environments. The animals channel surplus energy intake into a larger body mass, without being able to increase their rate of population growth accordingly.

The production of Cyprideis torosa Jones 1850 (Crustacea, Ostracoda).

The ostracod Cyprideis torosa Jones, 1850 is a dominant species in the meiofauna of brackish water habitats. Its production in the field over a five-year period has been calculated using two production models. The first model uses the age-distribution of shells preserved in the sediment to assess the stage-specific mortality rates and the stage durations. The second model is the size-frequency model, modified for use with developmental stages instead of size-classes. Productions calculated with both methods agree very well. Their values are 9.7 and 9.2 g dwt·m-2·y-1 respectively. The yearly P/B-ratio is 2.7 or 2.6 y-1, production efficiency P/A is 0.38 or 0.37.The production efficiency of Cyprideis torosa nearly equals the mean efficiency of non-insect invertebrate detritivores. The species' conservative strategy and long generation time enables it to maintain a relatively high biomass with a fixed amount of food. These characteristics make it a superior competitor.

Monoclonal IgM: difficulties with correct measurement.

We describe three monoclonal IgM paraproteins for which nephelometric IgM quantification generated inaccurate results.