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Sample bottle design improvements for radon emanation analysis of natural waters.

The "radon emanation" method of analysis for Rn and Ra in natural waters has been used by scientists for more than 30 years. We have examined the use of a new plastic bottle design as a viable option and improvement to traditional glass designs. The advantages of the new design over that used previously in our laboratory include a larger volume, lower blank, less fragile nature, and ease of handling in the field. Extensive calibration of the new design yielded an average efficiency of 70.9 +/- 1.7% and showed that an accurate blank value can be determined for each sample based on its specific holding time. Based on a 5-L sample and a 60-min count time, minimum detectable activities (MDA) range from 1.0 to 1.2 mBq L for Rn and Ra, respectively. Memory effect experiments have shown that activity artifacts are negligible when reusing the sampling containers. In addition, intra- and inter-laboratory comparisons show that the new design gives reliable results.

Calibration↗

Design and sample characteristics of the PRISM-E multisite randomized trial to improve behavioral health care for the elderly.

OBJECTIVE: To describe the design of the Primary Care Research in Substance Abuse and Mental Health for Elderly (PRISM-E) study and baseline characteristics of the randomized primary care patients with mental health problems and at-risk alcohol use. METHOD: Adults aged 65 and older were screened at primary care clinics from 10 study sites throughout the United States. Those diagnosed for depression, anxiety, and/or at-risk alcohol consumption were randomized to either integrated or enhanced referral care. RESULTS: Of the 23,828 participants, 14% had a positive assessment for depressive and/or anxiety disorders, and 6% had at-risk alcohol consumption diagnoses. Among patients with mental health diagnoses, there was a higher preponderance of younger ages, women, and ethnic minorities. Among patients with at-risk drinking, there was a higher preponderance of younger ages, Whites, and men. DISCUSSION: These findings indicate the need for screening in primary care and for engaging older adults in treatment.

Age Factors↗

A simulation study of methods for constructing confidence intervals for bioaccumulation factors.

Toxicokinetics describe the time course of xenobiotics in an exposed organism. The steady state concentration of the xenobiotic is a characteristic of frequent concern, often summarized in terms of bioaccumulation factors (BAFs). Two experimental protocols are commonly used when estimating BAFs: a continuous exposure experiment and a start-stop exposure experiment. Nonlinear regression is then used for estimating components of the BAF. A variety of methods are available for constructing confidence intervals (CI) for the BAF, including the delta method and Fieller's method. The properties of these CI methods are explored through a simulation study. In particular, the coverage properties of the two CI methods along with their interval widths are examined for a variety of time-course patterns, error distributions, experimental protocols, and sampling designs. Fieller's method is observed to exceed nominal coverage probabilities for all conditions considered (the coverage probability being the probability that a confidence interval contains a parameter it estimates over repeated experiments). The delta method exhibited observed coverage probabilities lower than nominally specified for a number of conditions. For sampling designs in which more of the sampling times are prior to steady state or the stop exposure time, the delta method is observed to provide nominal coverage probabilities with interval widths much narrower than observed with the Fieller's method. Thus, the delta method is preferable when the above sampling time condition is met; however, in all other cases, Fieller's method should be used.

Animals↗

Guide to using masked design variables to estimate standard errors in public use files of the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey.

Until recently, sample design information needed to correctly estimate standard errors from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) public use files was not released for confidentiality reasons. In 2002, masked sample design variables were released for the first time with the 1995-2000 NAMCS and NHAMCS public use files. This paper shows how to use masked design variables to compute standard errors in three software applications. It also discusses when masking overstates or understates "in-house" standard errors, and how masking affects the significance levels of point estimates and logistic regression parameters.

Adolescent↗

Regulatory environment and psychotropic use in board-and-care facilities: results of a 10-state study.

BACKGROUND: Largely unsupervised administration of drugs and the potential for overuse of psychotropic agents in residential care facilities have emerged as major public policy concerns. In a large multistate study, we examined patterns of psychotropic prescription and use by facility licensure status and the extensiveness of state regulations. METHODS: Descriptive analyses were based on a sample of 2,949 residents from 493 board-and-care facilities in 10 states, drawn via a complex, multistage sampling design. States were purposively selected based on the stringency of their board-and-care regulatory system, and samples of facilities were drawn, stratified by licensure status and home size. Residents were randomly selected within the sampled facilities. Weighted analyses were performed with Software for Survey Data Analysis (SUDAAN), accounting for the complex sampling design. RESULTS: Approximately 43% of the residents were prescribed and 41% used at least one psychotropic agent, primarily on a routinely scheduled basis. Antipsychotics were prescribed to 22% and used by 21%; antidepressants were prescribed to 17% and taken by 16%; antimanic agents were prescribed to and used by 4%; and anxiolytics, sedatives, or hypnotics were prescribed to 17% and used by 14%. Among psychotropic users, over 50% had not had mental health services in the prior year; 25% had no psychiatric history. Among licensed facilities, prescription and use of psychotropics, particularly antipsychotics, was significantly higher among residents of homes located in states with limited regulatory systems. CONCLUSIONS: Results revealed high rates of psychotropic prescription and use, and not inconsequential levels of polypharmacy - within and across therapeutic classes - among board-and-care facility residents. Frequently, psychotropics were not used as an adjunct to alternative treatments, and were not associated with a psychiatric history. Extent of psychotropic use was related to the regulatory environment, suggesting that more extensive regulations and monitoring may reduce psychoactive drug use in board-and-care facilities, and more adequately ensure the appropriateness of such treatment.

Adolescent↗

Power evaluations for family-based tests of association with incomplete parental genotypes.

While a variety of methods have been developed to deal with incomplete parental genotype information in family-based association tests, sampling design issues with incomplete parental genotype data still have not received much attention. In this article, we present simulation studies with four genetic models and various sampling designs and evaluate power in family-based association studies. Efficiency depends heavily on disease prevalence. With rare diseases, sampling affecteds and their parents is preferred, and three sibs will be required to have close power if parents are unavailable. With more common diseases, sampling affecteds and two sibs will generally be more efficient than trios. When parents are unavailable, siblings need not be phenotyped if the disease is rare, but a loss of power will result with common diseases. Finally, for a class of complex traits where other genetic and environmental factors also cause phenotypic correlation among siblings, little loss of efficiency occurs to rare disease, but substantial loss of efficiency occurs to common disease.

Data Interpretation, Statistical↗

The use of sequential designs in genome scans for asthma susceptibility loci with affected sib pairs.

We use optimized group sequential study designs to analyze data from two genome scans (German and CSGA) for asthma susceptibility loci with affected sib pairs from Genetic Analysis Workshop (GAW) 12. Results are compared with those from a fixed sample design and the sequential probability ratio test (SPRT). The SPRT does not reach significance at any position. Using the fixed sample design, evidence for linkage is found on chromosomes 6 and 9 in the German and on chromosome 1 in the CSGA scan. The group sequential designs identify the same regions on chromosomes 1 and 6 with a reduced sample size.

Adult↗

A multi-factor experimental design for evaluating random-access analyzers.

A multi-factor experimental design for evaluating random-access analyzers has been developed and tested for the Ciba Corning "550 Express" random-access analyzer. The 12-sample design estimates imprecision, slope, nonlinearity, linear drift, and reagent carryover to the next assay. The design was constructed so that estimates of the factors' effects are almost entirely uninfluenced by each other. Use of the design is illustrated by an example in which reagent-to-assay carryover was pinpointed as an apparent cause of high imprecision. This led to a modification of the analyzer such that carryover was insignificant. The appendix contains a 27-sample design that provides additional estimates. Software to perform such calculations is available on request.

Aspartate Aminotransferases↗

Forest health surveys--a critique.

Surveys of forest health, as presently undertaken, provide information on the general condition of forests. They integrate the effects of all factors, biotic and abiotic, of which pollution is but one, that affect trees. Most surveys are based on the assessment of crown density and crown discoloration. These assessments are subjective and serious errors can occur. In some cases, the sampling design that has been adopted is not the most suitable for the forest area under investigation. The blanket application of a systematic sampling design based on a 16 by 16 km grid is particularly questionable in view of the variation in the nature of Europe's forests. Comparisons, either between regions or through time, may or may not be valid, depending on how the surveys are conducted. Although much progress has been made, standardisation within Europe has not yet been achieved and it is therefore difficult to make comparisons between the results obtained by different countries.

Journal Article↗

Quantitative 13C NMR analysis of sequence distributions in poly(ethylene-co-1-hexene).

Different 13C NMR methods of determining triad distributions in two poly(ethylene-co-1-hexene) copolymers are examined using high signal-to-noise ratio 13C NMR spectra of the copolymers dissolved in deuterated 1,2,4-trichlorobenzene at 398 K. This examination includes a comparison of three integration techniques. The experimental impact of decoupler sidebands and significantly nonequal 13C NOE values are examined. A least-squares regression analysis technique for solving for triad mole fractions is tested and appears to be more reliable than two published algebraic expressions (and other expressions examined in the work reported here). The resultant triad mole fractions are compared to sequence distribution parameters expected by Bernoullian and first-order Markovian statistical models. On the basis of 13C NMR-determined average reactivity ratios, the copolymer designated sample B (5.3 mol % 1-hexene) appears to be a Bernoullian copolymer resulting from a single-site catalytic system. The copolymer designated sample S (3.6 mol % 1-hexene overall) is better described as a mixture of polyethylene and a Bernoullian copolymer with 6.4 mol % 1-hexene content, and thus appears to result from a multisite catalytic system.

Journal Article↗

National Family Health Survey.

The authors outline the organization and administration of India's National Family Health Survey, for which data collection was scheduled for completion in June 1993. Data analysis and survey objectives are discussed, as well as some political factors affecting data collection. It is noted that "the National Family Health Survey is...a large-scale sample survey covering 97 per cent of the population and involving more than 90,500 households.... Another feature of the NFHS is its uniformity in questionnaire design, sample design, data collection and analysis. This uniformity provides an opportunity for inter-state comparison."

Asia↗

Subthreshold psychiatric disorders in primary care: prevalence and associated characteristics.

BACKGROUND: The authors analyse the prevalence of subthreshold psychiatric disorders in primary care and their association with the patient's health perception, disability in daily activities and psychological distress. METHODS: Five-hundred and fifty-four primary care patients who completed a two-phase study were administered the Composite International Interview for Primary Health Care (CIDI-PHC) and other self-report measures. Unweighted and weighted prevalence estimates were obtained for ICD-10 formal disorders and subthreshold disorders defined by specific operational criteria. The impact of subthreshold disorders on health perception, disability in daily activities and psychological distress was analysed by using multiple regression models. RESULTS: The overall prevalence of subthreshold disorders exceeded that of ICD-10 disorders. Subjects with subthreshold disorders reported levels of psychological distress, disability in daily activities and perceived health comparable to those of patients with full-fledged ICD-10 disorders. When we analysed the associated health characteristics of individual subthreshold disorders, we found that each subthreshold disorder was characterized by poorer health perception, after adjusting for comorbidity with defined disorders and physical illness, age and gender. Disability in daily activities was increased in individuals with subthreshold depression and agoraphobia. LIMITATIONS: The number of cases with subthreshold panic and somatization is very small and does not allow one to draw any definite conclusions on their associated characteristics. To reduce non-response bias related to sampling design and refusals, adjusted sampling weights were computed. Since the study design in Bologna and Verona was different and Bologna patients scoring <4 on the General Health Questionnaire were not interviewed, individuals with minimal distress come from the Verona sample alone. CONCLUSIONS: Because of the prevalence and associated characteristics of subthreshold disorders, primary care physicians should attach adequate importance to the patient's perceived poor health, distress and inability to fulfil daily tasks. The clinical relevance of subthreshold disorders has also potential implications for ongoing revisions of classification systems.

Activities of Daily Living↗

Effect of different sampling techniques on odds ratio estimates using hospital-based cases and controls.

Potential biases introduced by the use of hospital admission records have rarely been discussed in the veterinary literature. Veterinary Medical Teaching Hospital (VMTH) patient records kept at the University of California, Davis (UCD) School of Veterinary Medicine provide a unique opportunity to perform in-depth analyses on the effect of different control selection (sampling) techniques on odds ratio (OR) estimates for disease risk factors in a retrospective case-control study. Horses with Corynebacterium pseudotuberculosis abscesses (134) and the (secondary) study base population (source for controls) were identified, and a 'gold standard' OR for each category of the factors admission type, age, breed and sex was derived. Example data were used to calculate sampling ratios (SRs), defined as the ratio between any sample proportion (of an arbitrary risk factor) and the study base proportion for this risk factor. Sampling ratios different from 1.0 introduced biases into the observed OR estimates, when compared with the 'gold standard' OR. Three randomized samples (simple random, stratified random, systematic sampling), one matched (on date of admission) and three different diagnosis samples ('colic', 'cuts and lacerations', 'fractures') were selected from the study base, and the SRs for all categories of the four factors were derived. The matched and two different disease samples ('colic' and 'fractures') had especially wide ranges of observed SRs (and large errors in the OR estimates), whereas simple random and systematic sampling had comparably narrow ranges (less biased OR estimates). For the three randomized sampling techniques under study, repeated sampling was used to derive SR distributions. The SRs were approximately normally distributed. Analysis of variance and covariance showed that simple random and systematic sampling provided SR distributions with means closest to 1.0 (expected value) and small standard deviations. The OR estimates obtained from records selected by these two sampling techniques therefore were least biased. The findings demonstrate the importance of selecting appropriate sampling techniques in addition to properly defining the study (base) population. Sampling design introduces uncertainty into the OR estimates. The direction of the bias, however, depends on the OR between factor and disease in the source population (the 'gold standard'), and on the direction and magnitude of the SR. When combining the results from single and repeated sampling we conclude that sampling design is most influential on the range of the observed SRs (single samples), on the absolute deviation of the SR from 1.0 (expressed as SR delta Mean) and on the SR standard deviation (SD) (repeated sampling).

Animals↗

The effect of cardiovascular and osteoarticular diseases on disability in older Italian men and women: rationale, design, and sample characteristics of the Progetto Veneto Anziani (PRO.V.A.) study.

OBJECTIVES: Describe the methodology and preliminary results of the Progetto Veneto Anziani (PRO.V.A.) Study, an observational study of the Italian population aged 65 and older DESIGN: Cross-sectional cohort observation. SETTING: Northern Italy. PARTICIPANTS: Italians aged 65 and older, living in both the community and nursing homes. MEASUREMENTS: At baseline, participants were interviewed at their homes and subsequently examined by nurses and physicians at the two study clinics using an extensive battery of clinical, instrumental, biochemical, and physical performance tests. Hand, knee, hip, and chest x-rays and bone densitometry were performed in 92% of the participants, and 99% of the participants consented to blood drawing and deoxyribonucleic acid analyses. The physician who performed the physical examination determined disease presence based on several components of the interview and examination. A further, comprehensive determination was performed with standardized algorithms using all the information collected on each participant, including hospital records surveillance, standardized x-ray readings, and blood assays. In one of the study sites, a brain magnetic resonance imaging was performed in a subsample of the participants (820 persons). RESULTS: Overall response rate to the baseline clinic visit was 77% for men and 64% for women. Co-presence of at least one cardiovascular disease (CVD) and at least one osteoarticular disease (OAD) was identified in 10%, 22%, and 29% of men and 9%, 24%, and 40% of women aged 65 to 74, 75 to 84, and 85 and older, respectively. Overall, the mean number of coexisting chronic conditions was 1.8 for men and 2.4 for women. CONCLUSIONS: The PRO.V.A. study has the potential to provide an original contribution to clarify the mechanisms whereby diseases cause disability in older men and women; the particular focus on CVD and OADs will make it possible to comprehensively evaluate the development of disability as it relates to these two important conditions.

Aged↗

Sample size for the exact conditional test under inverse sampling.

Inverse sampling is a sampling design in which one continues sampling subjects until one obtains a predetermined number of index subjects. This paper derives a procedure for calculation of the minimum required number of index subjects on the basis of the exact conditional test under inverse sampling. This paper studies quantitatively the effect on power calculations of the number of index subjects. To facilitate use of inverse sampling in study designs, this paper further provides a table that summarizes, in a variety of situations, the minimum required number of index subjects for powers equal to 0.90 and 0.80 at 0.05-level. It also includes a discussion on use of the approximation sample size formula derived on the basis of a variance-stabilizing transformation and large sample theory.

Analysis of Variance↗

Stability of finite difference deconvolution II: simulation studies.

Theoretical analysis of the stability of finite difference deconvolution (FDD) indicates that if the cumulative amount function is used to characterize the drug input the method is stable for any sampling schedule for an intravenous unit impulse response function. The analysis also indicates that the method is stable for an oral unit impulse response only for well designed sampling schedules. This article confirms these results through numerical simulation experiments. It is shown that the assumption that the unit impulse response is error-free has an influence on the performance of FDD which is generally of no practical significance, except possibly for the first few points estimated. It is also shown that there is no significant interaction between the statistical error due to data noise and the deterministic algorithm error. The major source of error in practice is likely to be the data noise in the input response function. The simulations confirm that, with the estimated cumulative amount function as the quantity estimated and, with a well designed sampling schedule for the case of an oral unit impulse response, FDD is in practice an accurate and stable method with acceptable precision under a typical error disturbance.

Algorithms↗

Serial versus sparse sampling in toxicokinetic studies.

PURPOSE: Sparse sampling in rodent toxicokinetics usually involves the collection of a single blood sample on a given study day from each animal in a treatment group. The samples are allocated to different time points, often allowing some replicates, and statistical inferences are then made about the concentration-time behavior of the test compound. The present study compared the results of one such analysis with those obtained from serial sampling as might be applied using satellite animals. METHODS: Ten rats each received a single oral dose of tritium-labeled compound X. Blood concentrations in each rat at 10 time points post-dose were determined by liquid scintillation counting. Individual peak concentrations of blood radioactivity (Cmax) and peak times (tmax) were recorded, and area-under-curve (AUC) values were calculated by trapezoidal rule. The mean AUC and Cmax of all 10 animals over all 10 time points, referred to as AUCtrue and Cmax,true, were used as points of reference. These values were then estimated using subsets of the data that simulated satellite-animal or sparse-sampling designs. First, several different sampling schedules of 5 bleeding times were stimulated by taking subsets of the full data set. For analysis using satellite animals, serial blood concentrations from subsets of 3 or 4 rats were used to calculate point and confidence-interval estimates of AUCtrue and Cmax,true by standard methods; all possible subsets of 3 or 4 of the 10 rats were considered. For sparse data analysis, a single concentration from each of the 10 rats was used to calculate both point and confidence-interval estimates of AUCtrue by the Bailer-Satterthwaite method, and point estimates of Cmax,true, according to several different designs of replication. Animals were randomly assigned to time points, and 1000 of over 50000 possible combinations were evaluated for each bleeding schedule. The average percent absolute errors of the point estimates were computed and, for the 95% confidence intervals, average widths were determined. RESULTS: For point estimates of AUCtrue, sparse sampling yielded average percent absolute errors of 7-13%. Percent errors for 3 and 4 satellite animals were 6-12% and 5-10%, respectively. For 95% confidence intervals, sparse sampling yielded widths of 24-90% of AUCtrue, whereas for 3 and 4 satellite animals widths were 37-50% and 24-34%, respectively. For Cmax,true point estimates from sparse-sampling and satellite-animal approaches had average percent absolute errors of 5-12% and 3-8%, respectively. The confidence-interval widths for Cmax,true from the satellite-animal approach were 15-24% of Cmax,true, but coverage did not achieve the nominal 95% for some choices of sampling times. CONCLUSIONS: By using proper study designs, one can limit the number of samples and the amount of blood drawn so as not to affect the animals' health status, yet still achieve the customary pharmacokinetic objectives in a toxicity study.

Animals↗

Efficiency of systematic sampling in histomorphometric bone research illustrated by hydroxyapatite-coated implants: optimizing the stereological vertical-section design.

The sampling efficiency of the unbiased stereological vertical-section method was analyzed in five hydroxyapatite-coated implants. They were inserted into humans and harvested after 1 year. To find an optimal sampling design for histomorphometric analyses, sampling efficiency was estimated by variance analyses at different sampling levels (humans, sections, fields of view, and number of counting items) and intensities. Only minor changes in variance were observed when the initial scheme was reduced to include just one of the two possible implant sides, every third field of view, and half the density of the probe; this reduced the total workload at the microscope to less than 10% for all sections. In addition, the number of sections for analysis could be reduced to every fourth section per implant (three to four sections for evaluation) without significantly increasing variance. The study demonstrated that biological variation contributed to the majority of the total observed variance. Optimizing the sampling design could significantly reduce the workload at the hard-tissue microtome and the microscope without reducing the quality of the data that were unbiased and that had low sampling variance as compared with the true biological variation.

Adult↗