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[Estimation of the variances of the variables in the Barcelona health survey].

Variance estimation of surveys with complex sampling designs (stratified or multistage design) is biased if design effects are not taken into account. In this article we estimate the variance of some of the variables included in the 1986 health interview survey of Barcelona (survey of 2,205 households--clusters--that were stratified by municipal district and by family size). We present a comparison of variance estimates using the Jackknife method and using the standard method (the one used for simple random samples). Jackknife method incorporates sampling desing effects for estimating the variance, as homogeneous pseudo-clusters are formed. This method leads to more accurate results than the other method especially when calculating global population estimates. Differences between these methods are not very important, whereas cluster design effects are more important for certain variables.

Analysis of Variance↗

An Epidemiologic Note on Verification Bias: Implications for Estimation of Rates.

Two-stage designs offer several advantages for purposes of test validation and prevalence estimation. These include enhanced precision and increased cost-efficiency. Cost efficiency is obtained when the best available verification criterion is too expensive to employ in a large-scale epidemiologic study. The use of two-stage (or double-sampling) designs permit the same inferences from application to only a subset of those who were screened (with the less expensive criterion) during stage one. The retesting of only some of the first stage respondents introduces a bias, however, if these are sampled on the basis of first stage screening results. The form of this bias is described and solutions for correcting estimates are provided. These solutions are applied to the data reported by Abbott and Volberg (1996) in their study of the New Zealand general population. Corrected estimates of the sensitivity and specificity of the South Oaks Gambling Screen are obtained and used to adjust the reported lifetime and current prevalence estimates. The value of multi-stage designs for validity assessment and prevalence estimation are briefly described.

Journal Article↗

Human exposure to toxic metals: factors influencing interpretation of biomonitoring results.

An important approach to assessment of risk from environmental and occupational exposures is biomonitoring which provides an estimate of the total dose absorbed and gives indirect access to determination of target site concentrations. It is also a tool for assessing residual exposure, when respiratory protection is used. The interest in biological effects from toxic metals has increased during the last decades, as large amounts of metals have been released into industrial areas, and it is estimated that approximately 150,000 Danish workers are exposed to various metals. Since biomonitoring results play an important role in decision-making regarding great health and economic impact, understanding the factors influencing validity of such data is essential. In the present survey, the toxic elements arsenic, cadmium, chromium, cobalt, lead and nickel are used as examples to illustrate the disturbing factors in the interpretation of biomonitoring results. The aim of collecting samples is to obtain a small and representative sample of subjects or of a subpopulation being investigated for specific purposes, e.g. the pollution at Mundelstrup, where arsenic exposure of inhabitants and workers engaged in removing contaminated soil was monitored. As exposures vary over time and between subjects, it should be recognized that sampling as well as analytical variations contribute both to bias and random errors. Also biomonitoring data are a function of demographic, lifestyle and geographic factors. Therefore, stratified sampling designs are of the utmost importance. Half-lives play an important role. For short half-lives below 10 h, no decision can be made on long-term exposure if only one urine sample has been taken. For arsenic, cobalt, chromium and nickel in urine measured at the end of a workweek (t1/2: 20-100 h), 2-3 samples should be taken to monitor a single worker, and the results should be interpreted from the average of the results. For groups of workers, it is recommended that results from at least 5-10 workers be used to obtain a useful group mean value. In general, pharmacokinetics modelling contributes to information on sampling time and sampling size. Intake of cobalt in mineral tablets containing soluble cobalt compounds was a factor with a large influence on blood and urinary levels. Age and gender influence the blood and urine concentrations of arsenic, cadmium, cobalt and lead, e.g. B-Pb in females is 20-30% lower than B-Pb in males.(ABSTRACT TRUNCATED AT 400 WORDS)

Environmental Exposure↗

Improved in vitro fertilization embryo quality and pregnancy rates with intracytoplasmic sperm injection of sperm from fresh testicular biopsy samples vs. frozen biopsy samples.

OBJECTIVE: To compare the outcomes of first-attempt IVF-intracytoplasmic sperm injection (ICSI) cycles when using fresh testicular biopsy samples vs. frozen biopsy samples. DESIGN: Retrospective chart review of 92 consecutive first-attempt IVF-ICSI cycles. SETTING: Two IVF programs. PATIENT(S): Forty consecutive first-attempt IVF-ICSI patients using sperm from fresh testicular biopsy samples and 52 consecutive first-attempt IVF-ICSI cycles using frozen testicular biopsy samples. INTERVENTION(S): Testicular biopsy, IVF-ICSI with fresh and frozen-thawed spermatozoa. MAIN OUTCOME MEASURE(S): Fertilization rates, embryo quality, pregnancy, delivery, and spontaneous abortion rates. RESULT(S): A significantly increased ICSI fertilization percentage was obtained with frozen testicular biopsy samples (76.5% +/- 3.1%) vs. fresh biopsy samples (68.3% +/- 2.6%). However, embryo quality, pregnancy, and delivery rates were higher in the fresh biopsy group. Mean embryo score was 4.54 +/- 0.31 and 3.62 +/- 0.2 in the fresh vs. frozen group, respectively. Chemical pregnancy rates (60% vs. 49.1%), clinical pregnancy rates (56.4% vs. 41.2%), and delivery rates (48.7% vs. 31.2%) were each higher in the fresh group vs. frozen group. Accordingly, the spontaneous abortion rate was lower in the fresh group (21.7%) vs. the frozen group (33.3%). CONCLUSION(S): Although the use of frozen biopsy samples has logistical advantages, we conclude it may be advantageous to use fresh testicular biopsy samples in IVF-ICSI cases whenever possible, as fresh specimens yielded significantly improved embryo quality, generally higher pregnancy rates, and lower spontaneous abortion rates.

Abortion, Spontaneous↗

Evidence for population growth in humans is confounded by fine-scale population structure.

Although many studies have reported human polymorphism data, there has been no analysis of the effect of sampling design on the patterns of variability recovered. Here, we consider which factors affect a summary of the allele-frequency spectrum. The most important variable to emerge from our analysis is the number of ethnicities sampled: studies that sequence individuals from more ethnicities recover more rare alleles. These observations are consistent with fine-scale geographic differentiation as well as population growth. They suggest that the geographic sampling strategy should be considered carefully, especially when the aim is to infer the demographic history of humans.

Humans↗

Low dietary iron availability is a major cause of anemia: a nutrition survey in the Lindi District of Tanzania.

A nutrition survey was conducted in the rural Lindi District of Tanzania to determine the magnitude of anemia and iron deficiency in different age and sex groups as related to nutritional status, parasitic infections, food iron intake, and socioeconomic factors. In a 30-cluster sampling design, 660 households were randomly selected and a total of 2320 subjects aged 6 mo to 65 y were examined. Iron status was assessed by measuring hemoglobin and erythrocyte protoporphyrin in a finger-prick sample: 55% of the subjects had anemia and 61% of the anemia was associated with iron deficiency (erythrocyte protoporphyrin > 125 micromol/mol heme). Preschool children (aged < 5 y) were the most affected; 84% were anemic (hemoglobin < 110 g/L). Fifty percent of the nonanemic preschool children and approximately 90% of all the severely anemic subjects were iron deficient. Hemoglobin was lower in schoolchildren (aged 5-14 y) and in adolescent and adult males (aged > or = 15 y) with a low body mass index. Parasitic infections were only associated with anemia and iron deficiency in schoolchildren and adolescent and adult males. Malaria was associated with anemia (P < 0.001), whereas schistosomiasis was associated with anemia and iron deficiency (P < 0.001 and P < 0.05, respectively). Hookworm infestation was associated with iron deficiency (P < 0.05) and with anemia (P < 0.01) only in adolescents and adults. A mainly cereal-based diet with additional legumes and green vegetables was found by in vitro tests to contain high amounts of total iron but of low bioavailability. Estimation of the amount of iron absorbed confirmed inadequate iron nutrition. Although anemia is a result of a synergism of a variety of causes, iron deficiency remains the major cause.

Adolescent↗

Lung volume measured by functional residual capacity in infants following first trimester amniocentesis or chorion villus sampling.

OBJECTIVE: To determine the incidence of respiratory problems and lung volume abnormalities in babies born after first trimester amniocentesis or chorion villus sampling. DESIGN: A prospective randomized study. SETTING: Harris Birthright Research Centre for Fetal Medicine, Paediatric Respiratory Laboratory, King's College Hospital. SUBJECTS: Babies of mothers who had undergone first trimester amniocentesis (n = 74) or chorion villus sampling (CVS) (n = 86) for fetal karyotyping because of advanced maternal age, parental anxiety or family history of chromosomal abnormality in the absence of parental chromosome re-arrangement. MAIN OUTCOMES: Respiratory distress in the neonatal period and lung volume as assessed by measurement of functional residual capacity (FRC). RESULTS: CVS was associated with a significantly higher incidence of neonatal respiratory distress, six infants in the CVS group but none in the amniocentesis group required admission to the special care baby unit because of respiratory distress (P less than 0.05). Although there was no significant difference in the mean FRC between the two groups (amniocentesis 29.7 ml/kg vs CVS 29.6 ml/kg) the overall incidence of FRC values less than 2.5th centile of the normal range was 9%. CONCLUSION: Both amniocentesis and CVS performed in the first trimester of pregnancy may impair antenatal lung growth.

Amniocentesis↗

Regression methods for assessing familial aggregation of disease.

This paper reviews methods for assessing familial aggregation of disease based on simple logistic regression models. Studies are based on a case-control sampling design, where the disease status of the first degree relatives of both cases and controls are obtained. Both 'proband predictive' and 'family predictive' models are discussed, and an example is given using a case-control sample from a lung cancer study in non-smokers. The methods are extended to characterize co-aggregation of two disorders, that is, presence of one disorder in the proband increases the risk of a second disorder in the relative. An example involving eating disorders and depression is given.

Case-Control Studies↗

The characteristics and use patterns of all-terrain vehicle drivers in the United States.

The consent decrees between the US Consumer Product Safety Commission and the major distributors of all-terrain vehicles (ATV), which were designed to address ATV-related injuries and deaths, expired in April, 1998. While national estimates of nonfatal and fatal injuries involving ATVs declined after the consent decrees went into effect 10 years ago, the injury estimates have stabilized in recent years. To gain a better understanding of current ATV use patterns, the CPSC sponsored a national probability survey of ATV drivers in the fall of 1997. The survey was designed to collect information about the characteristics and use patterns of ATV drivers and to quantify the numbers and types of ATVs in use. It employed a single stage list-assisted random-digit-dial sample design. This article describes the results of the survey, and discusses long term ATV usage trends.

Accidents, Traffic↗

Motivations to donate blood: demographic comparisons.

BACKGROUND: Understanding blood donor motivations is crucial to improving effectiveness of donor recruitment and retention programs. STUDY DESIGN AND METHODS: Data from a 1998 survey of 92,581 U.S. blood donors were used to evaluate factors influencing the decision to donate in various demographic groups. Data were weighted to adjust for response and sample design. RESULTS: Of 52,650 respondents, 45,588 gave whole-blood (WB) donations. Among all demographic groups, the major reasons to donate were altruism (75-87%) and awareness of the need for blood (34-43%). Except for first-time donors and those <or=25 years old, blood drive organizers and/or recruiters were more important than family and/or peers in encouraging donors (13-19% vs. 1-8%). Although 59 to 63 percent of donors said they would be encouraged to donate by reminders originating from the blood bank, for some, the contact would have a negative effect and discourage donation. Discouragement would be higher if they were reminded by a telephone call (14%) rather than by a letter or e-mail (4%) or an appeal (2%) from the blood bank. CONCLUSION: WB donations appear to be made primarily for altruistic reasons and in response to appeals for blood. Ways to build on this humanitarianism and take advantage of new communication routes, such as e-mail, need to be developed.

Altruism↗

Application of the combustion method in a closed flask to the lead determination in atmospheric aerosols.

The destruction of the filter for metal determination in atmospheric aerosols is an important step in the analysis. Nowadays the decomposition of this kind of sample has not been completely solved, so it is interesting to study new methods for filter sample attack. In the present work the application of the combustion method in a closed flask for mixed cellulose esters filter decomposition for lead determination is proposed. For this purpose optimum operating conditions as stopper flask design, sample size, flask volume, shaking time and volume and concentration of absorbing solution are established, and accuracy and precision of the proposed method using AAS for the measurements is given. The results obtained by the closed flask combustion are compared with those found by wet attack with HNO3. The method proposed is rapid, has low reagent contamination and no loss of lead by volatilization or by amalgamation occurs. This method shows an accuracy and a precision in good agreement with the standard method.

Air Pollutants, Occupational↗

Fluorescence correlation spectroscopy (FCS)--a highly sensitive method to analyze drug/target interactions.

Fluorescence Correlation Spectroscopy (FCS) a new analytical technology, allows binding properties to be determined very accurately in biological assays at the level of single molecules. At concentrations of > or = 10(-12) M, binding constants, on/off-rates, and even reaction/enzyme kinetics can be determined in real-time, and in sample volumes as low as 10(-9) microliters. The FCS technology can be applied to study molecular and cellular interactions in homogeneous assays. Assay times in the range of seconds in combination with nanoliter sample volumes allow FCS to be used for high throughput screening to identify new pharmaceutical lead structures or new pharmacological targets. FCS is fully compatible with standard microtiter plate formats. However, for high throughput screening, specially designed sample carriers containing many thousand sub-microliter sample wells may be used in combination with a nanopipetting and sample retrieval system.

Animals↗

Sampling schemes for estimating nerve fibre size. II. Methods for unifascicular nerve trunks.

The total number of myelinated fibres in four unifascicular tibial nerves from diabetic rats has been counted and measured in order to assess the merits of various schemes for estimating group mean fibre diameter. The average nerve trunk contained some 2960 fibres which were measured in just under five hours. With different sampling designs, the average measurement time per nerve was reduced to between 17 and 69 minutes, with little consequent loss of reliability or precision of estimated mean fibre size. The most efficient schemes were those taking systematic samples of squares or sectors. A modification of a method relying on complete strips across two diameters of each nerve was the least efficient sampling approach. It had the additional disadvantage of introducing systematic errors which could affect the accuracy of measurements made on nerve trunks with heterogeneous spatial distributions of fibre size and number. This paper completes an investigation into random sampling errors influencing morphometric estimates of fibre size based on uni- or multifascicular nerve trunks.

Animals↗

Group sequential design for comparative diagnostic accuracy studies.

In the field of diagnostic medicine, comparative clinical trials are necessary for assessing the utility of one diagnostic test over another. The area under the receiver operating characteristic (ROC) curve, commonly referred to as AUC, is a general measure of a test's inherent ability to distinguish between patients with and without a condition. Standardized AUC difference is the most frequently used statistic for comparing two diagnostic tests. In therapeutic comparative clinical trials with sequential patient entry, fixed sample design (FSD) is unjustified on ethical and economical grounds and group sequential design (GSD) is frequently used. In this paper, we argue that the same reasoning exists for the comparative clinical trials in diagnostic medicine and hence GSD should be utilized in this field for designing trials. Since computation of the stopping boundaries of GSD and data analysis after a group sequential test rely heavily on Brownian motion approximation, we derive the asymptotic distribution of the standardized AUC difference statistic and point out its resemblance to the Brownian motion. Boundary determination and sample size calculation are then illustrated through an example from a cancer clinical trial.

Area Under Curve↗

Categorical and continuous models of liability to externalizing disorders: a direct comparison in NESARC.

CONTEXT: Patterns of genetic, environmental, and phenotypic relationships among antisocial behavior and substance use disorders indicate the presence of a common externalizing liability. However, whether this liability is relatively continuous and graded, or categorical and class-like, has not been well established. OBJECTIVES: To compare the fit of categorical and continuous models of externalizing liability in a large, nationally representative sample. DESIGN: Categorical and continuous models of externalizing liability were compared using interview data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). SETTING: Face-to-face interviews conducted in the United States. PARTICIPANTS: Random sample of 43 093 noninstitutionalized adult civilians living in the United States. MAIN OUTCOME MEASURES: Lifetime and current (past 12 months) diagnoses of antisocial personality disorder, nicotine dependence, alcohol dependence, marijuana dependence, cocaine dependence, and other substance dependence. RESULTS: In the entire sample, as well as for males and females separately, using either lifetime or current diagnoses, the best-fitting model of externalizing liability was a continuous normal model. Moreover, there was a general trend toward latent trait models fitting better than latent class models, indicating that externalizing liability was continuous and graded, rather than categorical and class-like. CONCLUSIONS: Liability to externalizing spectrum disorders is graded and continuous normal in distribution. Research regarding etiology, assessment, and treatment of externalizing disorders should target externalizing liability over a range of severity. Current diagnoses represent extremes of this continuous liability distribution, indicating that conditions currently classified as subthreshold are likely to provide important information regarding liability to externalizing phenomena.

Adolescent↗

Assessing spatial coupling in complex population dynamics using mutual prediction and continuity statistics.

A number of important questions in ecology involve the possibility of interactions or "coupling" among potential components of ecological systems. The basic question of whether two components are coupled (exhibit dynamical interdependence) is relevant to investigations of movement of animals over space, population regulation, food webs and trophic interactions, and is also useful in the design of monitoring programs. For example, in spatially extended systems, coupling among populations in different locations implies the existence of redundant information in the system and the possibility of exploiting this redundancy in the development of spatial sampling designs. One approach to the identification of coupling involves study of the purported mechanisms linking system components. Another approach is based on time series of two potential components of the same system and, in previous ecological work, has relied on linear cross-correlation analysis. Here we present two different attractor-based approaches, continuity and mutual prediction, for determining the degree to which two population time series (e.g., at different spatial locations) are coupled. Both approaches are demonstrated on a one-dimensional predator-prey model system exhibiting complex dynamics. Of particular interest is the spatial asymmetry introduced into the model as linearly declining resource for the prey over the domain of the spatial coordinate. Results from these approaches are then compared to the more standard cross-correlation analysis. In contrast to cross-correlation, both continuity and mutual prediction are clearly able to discern the asymmetry in the flow of information through this system.

Models, Theoretical↗

Reproducibility of bacterial and copepod density assessment in bathing and artisanal fishing water of the Eastern Mediterranean.

Faecal bacteriological indicators and copepod density assessment are used to predict the environmental health of seawater for recreational bathing and artisanal fishing, respectively. The reproducibility of bacterial culture-count and copepod-microscopic density assessment after respective capturing of the sampled seawater on 0.22 microm Millipore filter and 150 microm mesh sieve copepod net, is determined. The paired t-test was performed to evaluate the reproducibility of each obtained parameter-mean in first and second simultaneous water samplings of a total of 10 sites selected along a 200 km distance, at about 500-1000 m offshore. The means of each bacterial indicator in colony forming units/100 ml of sea water in first versus (vs.) second sampling of the 10 sites, followed by the P values were: total bacterial count (6.3 x 10(2) vs. 6.2 x 10(2), P=0.958), Coliform count (3.9 x 10(2) vs. 2.6 x 10(2), P=0.212), Staphylococcus aureus (3.0 x 10(2) vs. 2.4 x 10(2), P=0.551), and Clostridium perfringens (1.4 x 10 vs. 0.4 x 10, P=0.298). However, the average copepod density in five microscopic fields at magnification of 100x in sample 1 vs. sample 2 were: (1.40 vs. 1.60 respectively, P=0.267). This sampling design along the 200 km coast, the used technique for capturing the indicators, and the quantitative laboratory assessment of the indicator densities resulted in high reproducibility with a non-significant difference between the first and second sampling within the 95% confidence limits (P>0.05), a data in support of future monitoring protocol of the environmental health of the coastal water of the Mediterranean sea.

Animals↗

Personal exposure to ultrafine particles in the workplace: exploring sampling techniques and strategies.

Recently, toxicological and epidemiological studies on health effects related to particle exposure suggest that 'ultrafine particles' (particles with an aerodynamic diameter of <100 nm) may cause severe health effects after inhalation. Although the toxicological mechanisms for these effects have not yet been explained, it is apparent that measuring exposures against mass alone is not sufficient. It is also necessary to consider exposures against surface area and number concentration. From earlier research it was hypothesized that results on number concentration and particle distributions may vary with distance to the source, limiting the reliability of estimates of personal exposure from results which were obtained using static measurement equipment. Therefore, a workplace study was conducted to explore the performance of measurement methods in a multi-source emission scenario as part of a sampling strategy to estimate personal exposure. In addition, a laboratory study was conducted to determine possible influences of both distance to source and time course on particle number concentration and particle size distribution. In both studies different measurement equipment and techniques were used to characterize (total) particle number concentration. These included a condensation particle counter (CPC), a scanning mobility particle sizer (SMPS) and an electrical low pressure impactor (ELPI). For the present studies CPC devices seemed to perform well for the identification of particle emission sources. The range of ultrafine particle number concentration can be detected by both SMPS and ELPI. An important advantage of the ELPI is that aerosols with ultrafine sizes can be collected for further analysis. Specific surface area of the aerosols can be estimated using gas adsorption analysis; however, with this technique ultrafine particles cannot be distinguished from particles with non-ultrafine sizes. Consequently, estimates based on samples collected from the breathing zone and scanning electron microscopic analysis may give a more reliable estimate of the specific surface area of the ultrafine particles responsible for personal exposure. The results of both the experimental and the workplace study suggest both spatial and temporal variation in total number concentration and aerosol size distribution. Therefore, the results obtained from static measurements and grab sampling should be interpreted with care as estimates of personal exposure. For evaluation of workplace exposure to ultrafine particles it is recommended that all relevant characteristics of such exposure are measured as part of a well-designed sampling strategy.

Aerosols↗