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PubMed2026

Genetic inference in social insects: The continued utility of microsatellites in the sociogenomic era.

Social insects differ from many other biological systems because colonies function as integrated reproductive, ecological, and evolutionary units, often conceptualized as superorganisms. This organization makes genetic inference inherently hierarchical, often requiring genotyping across multiple biological levels: the colony, the population, the individual, and, in some cases, the cellular level. Although whole-genome sequencing and single-nucleotide polymorphism (SNP)-based approaches are now widely used in population genomics, microsatellites or short tandem repeats (STRs) remain a useful approach for cost-effective, low-input, and highly replicated genotyping, particularly in the hierarchical sampling designs common in social insect studies. Here, we review the utility and limitations of microsatellites in social insect research using a three-tiered framework spanning colony-, population-, and individual- or cellular-level analyses. Across these scales, microsatellites are especially valuable for colony delimitation, kinship inference, diagnostic screening of known reproductive systems, and low-input genotyping. By comparing the suitability of microsatellites with that of SNP-based and broader genomic approaches across these applications, this review links marker choice to biological scale, sampling design, and inferential goal in studies of social insects.

Journal Article↗
PubMed1985

A covariance structure model for quantitative genetic research.

In this paper, we have presented a general covariance structure model for quantitative genetic research that incorporates measurement theory, components of variance, and regression theory for specification of structural relations among variance components. Each portion of the general model addresses specific issues important in delineating the genetic etiology of continuous traits. Through specification of a measurement model, genetic and environmental influences can be estimated independently of measurement error. Genetic and environmental sources of variance are defined from familial sampling designs through the components of variance model. Structural relationships among several traits at the genetic or environmental level can be specified through the regression model. The significance of parameters specified in each part of the model can be tested through model comparisons using a likelihood ratio chi-square test. We utilized the general model to test genetic covariance as a source of observed covariation of obesity and glucose tolerance in the Pima Indians. We initially applied the modeling approach using full-sib, half-sib sampling among the Pima with a second application including offspring as well as parental scores. Our initial applications of the methodology suggest that the covariance structure model can be a useful tool in genetic epidemiological research. Through model comparisons, our findings suggest that the association of glucose tolerance and obesity in the Pima is not due to a common set of genes but rather due to non-familial environmental influences. In conclusion, one task important for future research, as we see it, is the application of covariance structure models to other familial sampling designs and the evaluation of the usefulness of this approach through further applications to data.

Arizona↗
PubMed1995

Psychotropic use among older residents of board and care facilities.

OBJECTIVE: To describe patterns of psychotropic use as well as clinically relevant and concurrent nonpsychotropic use among older residents of board and care facilities in 10 states. METHODS: Weighted use rates were based on data from a sample of 2054 residents aged 65 and older from 410 facilities in 10 states, drawn via a complex, multistage sampling design. Data, including drug name, use frequency, and PRN use, were collected on all drugs taken by the resident during a 7-day period. During face-to-face interviews with residents and/or proxies, data were also collected on resident characteristics. SUBJECTS: The majority of subjects were female, white, and widowed. Average age was 82 years. Approximately 25% had a current mental or emotional condition, and 8% had been hospitalized for a psychiatric condition during the year before admission. More than half needed help with at least one activity of daily living. Forty percent had moderate or severe cognitive impairment, and 18% had received mental health care during the previous year. ANALYSES: Weighted descriptive analyses were performed with Software for Survey Data Analysis (SUDAAN), which accounts for the complex, multistage sampling design. RESULTS: Approximately 35% of the older residents used at least one psychoactive agent, with 30% of psychotropic users receiving two to four different psychotropic medications. Use rates decline with age, for psychotropics overall and for therapeutic classes. Results revealed potentially problematic polypharmacy in relation to drug duplication within therapeutic classes, use of multiple psychotropics across classes, and concurrent nonpsychotropic use. CONCLUSIONS: Compared with community-dwelling older adults, this study revealed high psychotropic use rates among older board and care facility residents. Overall, our results suggest that serious consideration be given to the apparent need for systematic drug utilization review, a potentially useful program that is mandated in other settings.

Aged↗
PubMed2006

Ovulation detection methods for urinary hormones: precision, daily and intermittent sampling and a combined hierarchical method.

BACKGROUND: We evaluate the performance of ovulation detection methods and present new approaches, including evaluation of methods for precision, combining multiple markers into a hierarchical system and using ovulation markers in intermittent sampling designs. METHODS: With serum LH peak day as the 'gold standard' of ovulation, we estimated accuracy and precision of ovulation day algorithms using 30 ovulatory menstrual cycles with daily urinary and serum hormones and transvaginal ultrasound. Sensitivity and specificity for estimating the presence of ovulation were tested using visually assessed ovulatory (30) and anovulatory (22) cycles. RESULTS: Sensitivity and specificity ranged from 70 to 100% for estimating presence of ovulation with twice-per-cycle, weekly, twice weekly, every-other-day and daily specimens. A combined hierarchical method estimated ovulation day using daily specimens within +/-2 days of the gold standard in 93% of cases. Accuracy of estimating ovulation day within +/-2 days using intermittent sampling ranged from 40% (weekly sampling) to 97% (every-other-day). CONCLUSIONS: A combined hierarchical algorithm using precise and accurate markers allows maximal use of available data for efficient and objective identification of ovulation using daily specimens. In intermittent sampling designs, the presence and the timing of ovulation can be estimated with good sensitivity, specificity and accuracy.

Adult↗
PubMed1993

Physicians' productivity and teaching responsibilities.

BACKGROUND: There is considerable concern about the impact of teaching responsibilities on physicians' productivity. Previous research employing independent sample designs has suggested that physicians who teach medical students are less productive then their nonteaching counterparts. METHOD: This study examined the productivity of 15 family practice faculty and third-year resident physicians practicing in the Family Medical Center of the University of Kentucky College of Medicine; in addition to the care of patients, the physicians were assigned to teach third-year medical students participating in an ambulatory primary care clerkship. The productivity of each physician (i.e., number of patients seen per half day) was measured during a four-month period in the spring of 1991. The physicians' levels of productivity with and without medical students were compared through the use of a paired-sample design. RESULTS: No significant difference in productivity levels was observed. CONCLUSION: Ambulatory-care teaching responsibilities may not diminish physicians' productivity in academic teaching practices.

Ambulatory Care↗
PubMed2006

Population pharmacokinetic model of fluvoxamine in rats: utility for application in animal behavioral studies.

The limitations of blood sampling in pharmacokinetic (PK)/pharmacodynamic (PD) studies in behavioral animal models could in part be overcome by a mixed effects modeling approach. This analysis characterizes and evaluates the population PK of fluvoxamine in rat plasma using nonlinear mixed effects modeling. The model is assessed for its utility in animal behavioral PK/PD studies. In six studies with a different experimental setup, study site and/or sampling design, rats received an intravenous infusion of 1, 3.7 or 7.3mg/kg fluvoxamine. A population three-compartment PK model adequately described the fluvoxamine plasma concentrations. Body weight was included as a covariate and mean population PK parameters for CL, V(1), V(2), Q(2), V(3) and Q(3) were 25.1 ml/min, 256 ml, 721 ml, 30.3 ml/min, 136 ml and 1.0 ml/min, respectively. Inter-individual variability was identified on CL (39.5%), V(1) (43.5%), V(2) (50.1%) and Q(2) (25.7%). A predictive check and bootstrap analysis confirmed the predictive ability, model stability and precision of the parameter estimates. Body weight was identified as a significant covariate of the inter-compartmental clearance Q(2). The pharmacokinetics was independent of factors such as dose, surgery (for instrumentation) and study site. The utility of the model in animal behavioral studies was demonstrated in a PK/PD analysis of the effects on REM sleep in which a sparse PK sampling design was used. By using the pertinent information from the population PK model, individual PK profiles and the PK/PD correlation could be adequately described.

Animals↗
PubMed1994

Confidence intervals for weighted proportions.

We investigate methods for the construction of confidence intervals for a proportion in a stratified two-stage sampling design with few events occurring in a small number of large, unequal size strata. The critical aspect is the incorporation of the weighting scheme into the construction of a single overall confidence interval. With small numbers of events, the binomial based methods may be inadequate since the normal approximation is not valid. Computer simulations compare coverage probability and bias for five methods of obtaining confidence intervals for proportions by combining: (1) binomial variances; (2) confidence intervals based on the F-distribution approximation to the cumulative binomial; (3) the binomial variance method with exact confidence limits when a zero prevalence occurs in any stratum; (4) confidence intervals based on the F-distribution using a rescaling factor; and (5) the binomial variance method with exact confidence limits using a rescaling factor. The method that performs best in terms of coverage probability is the combination of stratum specific confidence intervals based on the F-distribution using a rescaling factor. The methods involving the binomial variance tend to be negatively biased and the methods based on the F-distribution tend to be positively biased. Application of these methods with data from a study of adolescent depression that employs a stratified two-stage sampling design is consistent with these results.

Adolescent↗
PubMed2003

Empirical modelling of population sampling: lessons for designing sentinel surveillance.

BACKGROUND: In order to consider the practical viability of 1% sentinel area surveillance for health information in resource-poor settings where complete registration is unrealistic, the effects of different sampling procedures on the representativeness of 1% population samples have been investigated. METHODS: Using the 1991 census of England as a basis for modelling, 20 1% samples, each incorporating seven key parameters, were drawn at random from the overall dataset by each of eight different sampling procedures. Each sample was compared with the 'gold standard' of the overall census results, enabling comparisons between the different sampling procedures. RESULTS: Representativeness of the 1% samples varied considerably between parameters and sampling procedures. At one extreme, the proportion of males in the population was distributed such that different sampling methods had little effect. On the other hand, samples of a heterogeneous parameter such as the proportion of non-whites in the population depended greatly on the procedure used. Sampling smaller administrative units tended to be more accurate. However, sampling units using probability proportional to size generally gave less representative samples. Stratifying urban and rural populations in the samples had little effect. Multistage sampling, emulating typical demographic surveillance sites, also generally gave less representative samples. CONCLUSIONS: It is possible to achieve representative data by taking 1% of a national population in a sentinel surveillance approach, but sampling design can have an important influence on the outcome. This modelling supports the concept of 1% sentinel surveillance for health information in poorer settings, where complete data are unavailable.

Censuses↗
PubMed1999

Growth and fatness at three to six years of age of children born small- or large-for-gestational age.

OBJECTIVE: To compare young children 3 to 6 years of age who were born small-for-gestational age (SGA; <10th percentile for gestational age) or large-for-gestational age (LGA; >/=90th percentile) with those who were born appropriate-for-gestational age (10th-89th percentile) to determine whether there are differences in growth and fatness in early childhood associated with birth weight status. DESIGN AND METHODS: National sample of 3192 US-born non-Hispanic white, non-Hispanic black, and Mexican-American children 3 to 6 years of age (36-83 months) examined in the third National Health and Nutrition Examination Survey and for whom birth certificates were obtained. On the birth certificates, length of gestation from the mother's last menstrual period was examined for completeness, validity, and whether the pattern of missing (n = 141) and invalid data (n = 147) on gestation was random. Gestation was considered invalid when >44 weeks, or when at gestations of </=35 weeks, birth weight was inconsistent with gestation. To reclaim cases with missing or invalid data on gestation for analysis, a multiple imputation (MI) procedure was used. MI procedures are recommended when, as in this case, a critical covariate (length of gestation) is not missing at random, and complete-subject analysis may be biased. Using the results of the MI procedure, children were categorized, and growth outcome was assessed by birth weight-for-gestational age status. The growth outcomes considered in these analyses were body weight (kg), height (cm), head circumference (cm), mid-upper arm circumference (MUAC; cm), and triceps and subscapular skinfold thicknesses (mm). The anthropometric outcomes first were transformed to approximate normal distributions and converted into z scores (standard deviation units [SDU]) to scale the data for comparison across ages. Outcomes at each age then were estimated using regression procedures. SUDAAN software that adjusts variance estimates to account for the sample design was used in analysis for prevalence estimates and to calculate regression coefficients (in SDU). RESULTS: Over these ages, children born SGA remained significantly shorter and weighed less (-0.70 to -0.60 SDU). Children born LGA remained taller and weighed more (0.40-0.60 SDU). For weight and height among LGA children, there was a divergence from the mean with age compared with those born appropriate-for-gestational age (10th-89th percentile). Head circumference and MUAC followed these same patterns. The coefficients for MUAC show values for SGA children fairly consistently at about -0.50 SDU and children born LGA show increasing MUAC from +0.40 to +0.50 SDU from 36 to 83 months of age. As with weight, there is a trend toward increased MUAC coefficients with age. Measures of fatness (triceps and subscapular skinfolds), which are more prone to environmental influences, showed less association with birth weight-for-gestational age status. Only a single age group, the oldest (6 years of age) group showed a significant deficit in fatness for children born SGA. For children born LGA, there was an increase in fatness at both the triceps and subscapular sites after 3 years of age. CONCLUSION: These findings on a national sample of US-born non-Hispanic white, non-Hispanic black, and Mexican-American children show that children born SGA remain significantly shorter and lighter throughout early childhood and do not seem to catch up from 36 to 83 months of age. LGA infants remain longer and heavier through 83 months of age, but unlike children born SGA, children born LGA may be prone to an increasing accumulation of fat in early childhood. Thus, early childhood may be a particularly sensitive period in which there is increase in variation in levels of fatness associated with size at birth. These findings have implications for the evaluation of the growth of young children. The results indicate that intrauterine growth is associated with size in early childhood. (ABSTR

Adipose Tissue↗
PubMed1999

A community-based study of chronic fatigue syndrome.

BACKGROUND: Most previous estimates of the prevalence of chronic fatigue syndrome (CFS) have derived largely from treated populations, and have been biased by differential access to health care treatment linked with sex, ethnic identification, and socioeconomic status. OBJECTIVE: To assess the point prevalence of CFS in an ethnically diverse random community sample. DESIGN AND PARTICIPANTS: A sample of 28,673 adults in Chicago, Ill, was screened by telephone, and those with CFS-like symptoms were medically evaluated. MAIN OUTCOME MEASURES AND ANALYSES: Self-report questionnaires, psychiatric evaluations, and complete medical examinations with laboratory testing were used to diagnose patients with CFS. Univariate and multivariate statistical techniques were used to delineate the overall rate of CFS in this population, and its relative prevalence was subcategorized by sex, ethnic identification, age, and socioeconomic status. RESULTS: There was a 65.1% completion rate for the telephone interviews during the first phase of the study. Findings indicated that CFS occurs in about 0.42% (95% confidence interval, 0.29%-0.56%) of this random community-based sample. The highest levels of CFS were consistently found among women, minority groups, and persons with lower levels of education and occupational status. CONCLUSIONS: Chronic fatigue syndrome is a common chronic health condition, especially for women, occurring across ethnic groups. Earlier findings suggesting that CFS is a syndrome primarily affecting white, middle-class patients were not supported by our findings.

Adult↗
PubMed1995

Optimal experimental design and sample size for the statistical evaluation of data from somatic mutation and recombination tests (SMART) in Drosophila.

In genetic toxicology it is important to know whether chemicals should be regarded as clearly hazardous or whether they can be considered sufficiently safe, which latter would be the case from the genotoxicologist's view if their genotoxic effects are nil or at least significantly below a predefined minimal effect level. A previously presented statistical decision procedure which allows one to make precisely this distinction is now extended to the question of how optimal experimental sample size can be determined in advance for genotoxicity experiments using the somatic mutation and recombination tests (SMART) of Drosophila. Optimally, the statistical tests should have high power to minimise the chance for statistically inconclusive results. Based on the normal test, the statistical principles are explained, and in an application to the wing spot assay, it is shown how the practitioner can proceed to optimise sample size to achieve numerically satisfactory conditions for statistical testing. The somatic genotoxicity assays of Drosophila are in principle based on somatic spots (mutant clones) that are recovered in variable numbers on individual flies. The underlying frequency distributions are expected to be of the Poisson type. However, some care seems indicated with respect to this latter assumption, because pooling of data over individuals, sexes, and experiments, for sample, can (but need not) lead to data which are overdispersed, i.e., the data may show more variability than theoretically expected. It is an undesired effect of overdispersion that in comparisons of pooled totals it can lead to statistical testing which is too liberal, because overall it yields too many seemingly significant results. If individual variability considered alone is not in contradiction with Poisson expectation, however, experimental planning can help to minimise the undesired effects of overdispersion on statistical testing of pooled totals. The rule for the practice is to avoid disproportionate sampling. It is recalled that for optimal power in statistical testing, it is preferable to use equal total numbers of flies in the control and treated series. Statistical tests which are based on Poisson expectations are too liberal if there is overdispersion in the data due to excess individual variability. In this case we propose to use the U test as a non-parametric two-sample test and to adjust the estimated optimal sample size according to (i) the overdispersion observed in a large historical control and (ii) the relative efficiency of the U test in comparison to the t test and related parametric tests.

Animals↗
PubMed2000

Monitoring age-related changes of collagen content and vascularity in ganglia using unbiased stereological methods.

We describe for the first time application of unbiased stereological techniques to estimate total volume and volume fractions of interest in individual dorsal root ganglia (DRG). Volume estimates were obtained using a two-stage sampling design. Sections were systematically sampled following a random start, from DRG which were embedded in methacrylate and exhaustively sectioned. We further examined the efficiency of point counting irregular volume fractions housed in a regular reference volume. We found that the precision of volume estimates was relatively unaffected by exhaustive sampling, and that the magnitude of error was, in large part, determined by object shape.

Adolescent↗
PubMed2006

The study of fat redistribution and metabolic change in HIV infection (FRAM): methods, design, and sample characteristics.

The Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM), initiated in 2000, investigates the prevalence and correlates of changes in fat distribution, insulin resistance, and dyslipidemia among human immunodeficiency virus (HIV)-infected men and women compared with a population-based group of control men and women. Between June 2000 and September 2002, 1,480 participants (1,183 HIV-infected persons and 297 controls) were enrolled in FRAM. Measurements taken included whole-body magnetic resonance imaging for quantification of regional fat, anthropometric measurements, central laboratory analysis of metabolites, and assessment of symptoms, sociodemographic factors, and lifestyle. Similar measurements were repeated among FRAM participants 4 years later (FRAM 2) for investigation of the progression of fat distribution changes, insulin resistance, and hyperlipidemia. In FRAM 2, which is ongoing, investigators are also determining the associations of subclinical cardiovascular disease, as measured by carotid intimal-medial wall thickness, with HIV infection, fat distribution changes, insulin resistance, and other proatherogenic changes in serum lipid levels. The demographic characteristics of HIV-infected FRAM men and women were comparable to those reported from a national random sampling of HIV-infected men and women receiving medical care in the United States. The representativeness of the FRAM sample increases its value as a resource for studies on fat distribution, metabolic changes, and atherosclerosis in HIV infection.

Adipose Tissue↗
PubMed1990

A proposal for using previous experience in designing microbiological sampling plans based on variables.

A microbiological sampling system on the basis of variables is presented which requires only small numbers of replicates (n greater than or equal to 2). The system uses previous data on standard deviations of numbers of micro-organisms in batches and is particularly useful for in-plant situations. The discriminating power of the system is comparable to that of the current International Committee on Microbiological Specifications for Foods sampling schemes but uses more replicates.

Bacteriological Techniques↗
PubMed1992

Parity as a correlate of adult female urinary incontinence prevalence.

STUDY OBJECTIVE: The aim was to investigate the possible association between parity, as indicated by the number of childbirths, and prevalence of urinary incontinence in an adult female population sample. DESIGN AND SETTING: A sample of 3114 women aged 30-59 years was selected at random from the population of Aarhus, Denmark, and mailed a self administered questionnaire on urinary incontinence and, among other things, parity. PARTICIPANTS: A total of 2631 questionnaires was returned (85%) with a slight but significant decrease in respondency by age. MAIN RESULTS: The 1987 urinary incontinence period prevalence was 17%. Seventy eight percent were parous, and 24% had had three or more childbirths. In women aged 30-44 years, the prevalence of urinary incontinence was found to be associated with parity and, in women aged 45 years and more, with three or more childbirths. In parous women 30-44 years of age, the prevalence of urinary incontinence increased with age at least childbirth and, in women aged 45 years and over, it increased with increasing parity but decreased with increasing age at first childbirth. In parous women, no association was found with time since last childbirth. Among clinical types of urinary incontinence, stress incontinence consistently showed the strongest associations with indicators of parity. In women aged 30-44 years, nearly two thirds of the 1987 prevalence of stress incontinence could be attributed to parity. CONCLUSIONS: These findings support the hypothesis that pregnancy and childbirth are potent causes of female urinary incontinence, so that they exert considerable impact on the level of population urinary incontinence prevalence. In the individual woman, the effect seems to be cumulative and long lasting but fades with age.

Adult↗
PubMed2003

Do psychological measures predict the ability of lower limb amputees to learn to use a prosthesis?

OBJECTIVE: Can psychological tests predict whether, on admission to a rehabilitation ward post amputation, a lower limb amputee will learn to use a prosthesis during the ensuing inpatient rehabilitation programme? DESIGN: A one-sample design in which psychological variables, and transfemoral/transtibial amputation site were tested as predictors of outcome. SETTING: An inpatient rehabilitation unit in the UK offering prosthetic provision. SUBJECTS: Forty-three consecutive patients with peripheral vascular disease (mean age 66.35 years, standard deviation 14.99) who had received an amputation on average 19 days previously on a surgical ward and were transferred to the unit for rehabilitation including assessment for prosthetic provision. MAIN OUTCOME MEASURE: Whether the patient learnt to use a prosthesis independently during the stay on the rehabilitation unit. RESULTS: During their stay in the rehabilitation unit (mean length of stay = 42 days), 31 patients learnt to use a prosthesis and 12 did not. A forward stepwise logistic regression revealed that the Kendrick Object Learning Test score on admission correctly predicted outcome in 70% of cases. The predictive power rose to 81% correct when the amputation site (transfemoral or transtibial) was included amongst the predictors. Anxiety, depression and recovery locus of control scores were not significant predictors of functional prosthetic use in this study. CONCLUSION: A simple test of learning ability and the amputation site can help to predict the patient's ability to learn to use a prosthesis following amputation and is recommended as part of the assessment process.

Aged↗