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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↗

Sample designs and sampling methods for the Collaborative Psychiatric Epidemiology Studies (CPES).

This paper provides an overview of the probability sample designs and sampling methods for the Collaborative Psychiatric Epidemiology Studies (CPES): the National Comorbidity Survey Replication (NCS-R), the National Study of American Life (NSAL) and the National Latino and Asian American Study of Mental Health (NLAAS). The multi-stage sample design and respondent selection procedures used in these three studies are based on the University of Michigan Survey Research Center's National Sample designs and operations. The paper begins with a general overview of these designs and procedures and then turns to a more detailed discussion of the adaptation of these general methods to the three specific study designs. The detailed discussions of the individual study samples focus on design characteristics and outcomes that are important to analysts of the CPES data sets and to researchers and statisticians who are planning future studies. The paper describes how the expected survey cost and error structure for each of these surveys influenced the original design of the samples and how actual field experience led to changes and adaptations to arrive at the final samples of each survey population.

Adult↗

Small sample studies: unique contributions for large sample outcome studies.

There are many important issues relevant to the course of illness and outcome of chronic psychiatric disorders that are not readily amenable to investigation with existing large sample, quantitative methodology. For example, complex interactive phenomena that change over time, such as the longitudinal impact of changes in social and work function on levels of symptomatology, are particularly difficult to quantify and assess in large n studies. Small sample studies are advantageous because they offer the ability to examine the longitudinal interplay of a wide range of variables in individual patients. The small n approach is useful for delineating important new course variables, developing models of course change, and generating unique research hypotheses. In this article, small sample "qualitative" methodology is reviewed, and data derived from recent small n, intensive longitudinal studies are presented. Methodological issues related to addressing qualitative data in large sample, controlled studies are addressed, and specific research hypotheses generated by small sample studies for consideration in future large sample outcome studies are suggested. It is concluded that small sample studies offer unique contributions to the understanding of the determinants of course of illness.

Follow-Up Studies↗

Opportunistic sampling from early childhood centres: a substitute for random sampling to determine lead and iron status of pre-school children?

This report compares the results from two sampling strategies used to determine the prevalence of elevated blood lead concentrations and iron status in 12-36 month old children in Central Sydney. The two methods were stratified random sampling using census collector districts and an opportunistic sampling strategy using client registers at Early Childhood Centres (ECCs). The response rates were 75.3% (n = 718 of whom 198 were aged 12-36 months) and 24.1% (n = 304) respectively. The geometric mean blood lead concentrations were 0.40 and 0.34 mumol/L respectively (p = 0.001). The traditional random sampling prevalence survey identified a significantly higher proportion of children with blood lead concentrations greater than 0.48 (OR = 0.61, 95% CI 0.40-0.93) and 0.72 mumol/L (OR = 0.44, 95% CI 0.21-0.92) compared to the simpler opportunistic survey. The median plasma ferritin concentration for both studies was 19 micrograms/L (p = 0.4). The prevalence of iron depletion, iron deficiency and iron deficiency anaemia was not significantly different between the two studies. In conclusion, opportunistic sampling through ECCs does not appear to be a substitute for the traditional random sampling prevalence surveys of determine the prevalence of elevated blood lead concentrations in pre-school children in Central Sydney. However, opportunistic sampling through ECCs may be an appropriate method for monitoring iron status, in particular iron depletion, in pre-school children in Central Sydney.

Anemia, Iron-Deficiency↗

Injury surveillance in accident and emergency departments: to sample or not to sample?

OBJECTIVES: To establish whether injury surveillance based on sampling strategies is as valid as total patient surveillance. METHODS: Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) data for 1996 were retrospectively analysed using five sampling frames. Proportions for key variables were calculated for each sample, then compared with the proportions for the total population of patients. RESULTS: Two of the five sampling frames produced statistically significant differences from the total population, which can be explained by seasonal variations. However, no significant differences were observed between the remaining three samples and the total population. CONCLUSIONS: A well planned and executed sampling strategy can generate as valid data as total patient surveillance, obviating the need for data collection on every patient presenting with an injury or poisoning. In practice, however, systematic sampling can be difficult to implement and sustain, counterbalancing the economic advantages.

Adolescent↗

Evaluation of a sparse sampling strategy for determining vancomycin pharmacokinetics in preterm neonates: application of optimal sampling theory.

OBJECTIVE: To use optimal sampling theory to determine the fewest vancomycin concentrations required and the appropriate sampling times to calculate vancomycin pharmacokinetic parameters in neonates. DESIGN: Unblinded evaluation in neonates with presumed sepsis. SETTING: Level 3 community-based neonatal intensive care unit. PATIENTS: Eleven neonates with presumed sepsis. INTERVENTIONS: Twelve courses of intravenous vancomycin 20 mg/kg were administered. Blood samples were collected 3 and 9 hours after initiation of a 1-hour infusion of the first dose. MEASUREMENTS AND MAIN RESULTS: A two-compartment model was fit to vancomycin concentrations using iterative two-stage analysis. Pharmacokinetic parameter estimates were used for determination of optimal sampling times for two-, three-, and four-sample strategies with subsequent generation of two-, three-, and four-sample concentration data for 100 cases. Relative performance of strategies was compared through calculation and comparison of D efficiency for the determined strategies. Bias (median percent error) and precision (median percent absolute error) of pharmacokinetic parameter estimates for each strategy in the 100 simulated cases were determined. CONCLUSIONS: For estimation of total clearance and volume in the central and peripheral compartments, all strategies performed similarly with no difference in efficiency or bias and precision of estimates. Our results suggest that for clinical evaluations two appropriately timed samples (0.5 h after a 1-h infusion, trough concentration) are adequate for estimation of vancomycin clearance in neonates.

Aminoglycosides↗

National probability samples in studies of low-prevalence diseases. Part II: Designing and implementing the HIV cost and services utilization study sample.

OBJECTIVE: The design and implementation of a nationally representative probability sample of persons with a low-prevalence disease, HIV/AIDS. DATA SOURCES/STUDY SETTING: One of the most significant roadblocks to the generalizability of primary data collected about persons with a low-prevalence disease is the lack of a complete methodology for efficiently generating and enrolling probability samples. The methodology developed by the HCSUS consortium uses a flexible, provider-based approach to multistage sampling that minimizes the quantity of data necessary for implementation. STUDY DESIGN: To produce a valid national probability sample, we combined a provider-based multistage design with the M.D.-colleague recruitment model often used in non-probability site-specific studies. DATA COLLECTION: Across the contiguous United States, reported AIDS cases for metropolitan areas and rural counties. In selected areas, caseloads for known providers for HIV patients and a random sample of other providers. For selected providers, anonymous patient visit records. PRINCIPAL FINDINGS: It was possible to obtain all data necessary to implement a multistage design for sampling individual HIV-infected persons under medical care with known probabilities. Taking account of both patient and provider nonresponse, we succeeded in obtaining in-person or proxy interviews from subjects representing over 70 percent of the eligible target population. CONCLUSIONS: It is possible to design and implement a national probability sample of persons with a low-prevalence disease, even if it is stigmatized.

Data Collection↗

Sample design, sampling weights, imputation, and variance estimation in the 1995 National Survey of Family Growth.

OBJECTIVES: Cycle 5 of the National Survey of Family Growth (NSFG) was conducted by the National Center for Health Statistics (NCHS) in 1995. The NSFG collects data on pregnancy, childbearing, and women's health from a national sample of women 15-44 years of age. This report describes how the sample was designed, shows response rates for various subgroups of women, describes how the sampling weights were computed to make national estimates possible, shows how missing data were imputed for a limited set of key variables, and describes the proper ways to estimate sampling errors from the NSFG. The report includes both nontechnical summaries for readers who need only general information and more technical detail for readers who need an in-depth understanding of these topics. METHODS: The 1995 NSFG was based on a national probability sample of women 15-44 years of age in the United States and was drawn from 14,000 households interviewed in the 1993 National Health Interview Survey (NHIS). Of the 13,795 women eligible for the NSFG, 10,847 (79 percent) gave complete interviews. RESULTS: This report recommends using weighted data for analysis and a software package that will estimate sampling errors from complex samples (for example, SUDAAN or comparable software). The rate of missing data in the 1995 NSFG was very low. However, missing data were imputed for 315 key variables, called "recodes." Of the 315 recodes defined for Cycle 5, 271 variables had missing data on less than 1 percent of the cases; only 44 had 1 percent or more with missing data. These missing values were imputed for all of these 315 variables. The imputation procedures are described in this report.

Adolescent↗

pH-mediated field-amplified sample stacking of pharmaceutical cations in high-ionic strength samples.

Capillary electrophoretic separation of samples of physiological origin typically have both poor resolution and efficiency due to destacking. We have previously reported a stacking method for concentration of catecholamines in artificial dialysate, or Ringer's solution. However, pH-mediated sample stacking of other cations has not been investigated. In this report, pH-mediated stacking has been extended to eletripan, dofetilide, doxazosin, sildenafil, UK-103,320, UK-202,581, and CP-122,288. These compounds were chosen without prior structural screening except that they were cationic at the pH of our background electrolyte (BGE). Capillary electrophoretic behavior of samples in BGE is compared with those of samples in Ringer's solution with and without pH-mediated acid stacking. Results indicate that the peak heights and efficiencies for acid-stacked samples are increased compared to the unstacked samples in Ringer's solution or BGE. For example, the peak efficiencies for 5 s injections of eletriptan in BGE and Ringer's solution are 138,000 and 72,000 plates, respectively. In contrast, a 10 s injection of eletriptan followed by acid injection for 16 s produces a peak with 246,000 plates. Evaluation of the stacking effect was performed by comparison of the peak height at similar peak efficiencies for samples in Ringer's solution with and without stacking. Using this method, pH-mediated acid stacking provides a 10- to 27-fold sensitivity enhancement for the seven cations.

Cations↗

Quantitative microscopic analysis of inflammation in rheumatoid arthritis synovial membrane samples selected at arthroscopy compared with samples obtained blindly by needle biopsy.

OBJECTIVE: To evaluate microscopic measures of inflammation in rheumatoid arthritis synovial tissue samples selected at arthroscopy compared with those obtained blindly by needle biopsy from the suprapatellar pouch (SPP) of the same joint. METHODS: Samples were selected at knee arthroscopy from the SPP and the lateral and medial gutters. Immediately following arthroscopy, a biopsy needle was inserted through the same portal into the SPP by a second investigator, and 3 further samples were obtained blindly. Using standard immunohistologic methods, all samples were analyzed by a single investigator without knowledge of the original tissue location and biopsy technique. Following staining with anti-CD3 and anti-CD68 monoclonal antibodies, T lymphocyte and macrophage infiltration were measured by quantitative analysis. RESULTS: Synovial tissues from 14 patients were analyzed. In comparing microscopic measures of inflammation using the 2 procedures, mean scores of lining cell depth and the percentage of CD68+ cells in the lining layer correlated positively (tau = 0.59, P = 0.003 and tau = 0.73, P = 0.0003, respectively). In the sublining layer, CD3+ cell counts also correlated significantly (tau = 0.71, P = 0.0004). Sublining CD68+ cell counts did not correlate. This was explained by the observation that CD68+ cell infiltration in areas adjacent to articular cartilage was significantly greater than in the SPP (P = 0.01), suggesting preferential trafficking to this site by macrophages, but not by T lymphocytes. Macroscopic appearance at arthroscopy did not predict microscopic features. CONCLUSION: Most microscopic measures of inflammation in synovial tissue samples obtained blindly from the SPP were similar to those determined in samples selected at arthroscopy. However, measurements in samples from the SPP may underestimate the intensity of macrophage infiltration in areas more adjacent to cartilage. These observations have important implications for future study of macrophage function in synovial tissue.

Arthritis, Rheumatoid↗

The automatic sampling shield: a device for sampling suckled breast milk.

The automatic sampling shield uses the negative pressure exerted by the breast-feeding baby during sucking to withdraw a series of small samples from the milk stream. Shield performance was studied at four feeds for each of 13 babies. Acceptance of the shield was good (96% of feeds) and samples were obtained in 88% of feeds. Sample weight was large enough for micro-biochemical analysis of composition (median weight 1.3 g), without depriving the baby of important amounts of milk (median percentage of weight of milk intake was 4.3% and sample weight was less than 5 g in all cases). The shield should sample a constant proportion throughout the feed, in order to obtain a sample that is representative of the infant's nutrient intake. Fractional test-weighing of feeds showed a tendency for a larger proportion of the feed to be collected at slower flow rates. Modelling on the basis of the observed flow profiles in conjunction with a theoretical fat concentration profile showed that the observed 'disproportionality' would have over-estimated fat intake by a mean of 2.6% per feed (S.D.9.1 range -18.9% to + 16.9%). Using the shield in random sequence at two out of the first four feeds after 0800 h, showed that an infant's mean milk intake with the shield was on average 32% less than on control feeds. Allowing for possible compensation by the infant when control feeds followed low shield intakes, mean milk intakes with the shield were 17% smaller than without the shield.

Breast Feeding↗

X-ray fluorescence analysis of geological samples: exploring the effect of sample thickness on the accuracy of results.

The accuracy of the simple quantitative method of elemental XRF analysis applied to thick and thin geological samples was investigated with certified reference materials. In the case of thick samples, the intensity of the calcium signal was used as a characteristic of the sample for the dark matrix correction, as it had been found to be inversely correlated with the intensity of the silicon signal. The results of the analysis of thick samples did not depend on the sample form (pressed disc or a powder in a cup), and the absorption factors were very high. In the analysis of thin samples, the detection limits, sensitivity, and accuracy have been improved, particularly for light elements. As the absorption factors are close to unity for thin samples, there is no need for a matrix-effect correction or certified reference materials.

Journal Article↗

Natural sample fractionation by FlFFF-MALLS-TEM: sample stabilization, preparation, pre-concentration and fractionation.

Two flow field flow fractionation (FlFFF) systems: symmetrical (SFlFFF) and asymmetrical (ASFlFFF) were evaluated to fractionate river colloids. Samples stability during storage and colloids concentration are the main challenges limiting their fractionation and characterization by FlFFF. A pre-fractionation (<0.45 microm) and addition of a bactericide such as NaN3 into river colloidal samples allowed obtaining stable samples without inducing any modification to their size. Stirred cell ultra-filtration allowed colloidal concentration enrichment of 25-folds. Scanning electron microscope (SEM) micrographs confirmed the gentle pre-concentration of river samples using the ultra-filtration stirred cell. Additionally, larger sample injection volume in the case of SFlFFF and on channel concentration in the case of ASFlFFF were applied to minimize the required pre-concentration. Multi angle laser light scattering (MALLS), and transmission electron microscope (TEM) techniques are used to evaluate FlFFF fractionation behavior and the possible artifacts during fractionation process. This study demonstrates that, FlFFF-MALLS-TEM coupling is a valuable method to fractionate and characterize colloids. Results prove an ideal fractionation behavior in case of Brugeilles sample and steric effect influencing the elution mode in case of Cézerat and Chatillon. Furthermore, comparison of SFlFFF and ASFlFFF fractograms for the same sample shows small differences in particle size distributions.

Colloids↗

A sample preparation process for LC-MS/MS analysis of total protein drug concentrations in monkey plasma samples with antibody.

The determination of protein concentrations in plasma samples often provides essential information in biomedical research, clinical diagnostics, and pharmaceutical discovery and development. Binding assays such as ELISA determine meaningful free analyte concentrations by using specific antigen or antibody reagents. Concurrently, mass spectrometric technology is becoming a promising complementary method to traditional binding assays. Mass spectrometric assays generally provide measurements of the total protein analyte concentration. However, it was found that antibodies may bind strongly with the protein analyte such that total concentrations cannot be determined. Thus, a sample preparation process was developed which included a novel "denaturing" step to dissociate binding between antibodies and the protein analyte prior to solid phase extraction of plasma samples and LC-MS/MS analysis. In so doing, the total protein analyte concentrations can be obtained. This sample preparation process was further studied by LC-MS analysis with a full mass range scan. It was found that the protein of interest and other plasma peptides were pre-concentrated, while plasma albumin was depleted in the extracts. This capability of the sample preparation process could provide additional advantages in proteomic research for biomarker discovery and validation. The performance of the assay with the novel denaturing step was further evaluated. The linear dynamic range was between 100.9ng/mL and 53920.0ng/mL with a coefficient of determination (r(2)) ranging from 0.9979 and 0.9997. For LLOQ and ULOQ samples, the inter-assay CV was 12.6% and 2.7% and inter-assay mean accuracies were 103.7% and 99.5% of theoretical concentrations, respectively. For QC samples, the inter-assay CV was between 2.1% and 4.9%, and inter-assay mean accuracies were between 104.1% and 110.0% of theoretical concentrations.

Animals↗

Evaluation of activated carbon fiber filter for sampling of organochlorine pesticides in environmental water samples.

A simple method for quantitative analyses of organic chlorine pesticides (OCPs) in environmental water samples such as rainwater, river water and seawater using activated carbon fiber filters (ACFF) is described. ACFF was used as adsorbent to collect the chemicals in water samples. The collection of OCPs was completed almost for one day by stirring the mixture of the sample and the ACFF chips at room temperature. The adsorbed OCPs on the ACFF could be extracted easily with toluene-ethanol (4:1) mixed solvent. The purified extract by a florisil column chromatograph was followed by the analysis using high-resolution gas chromatograph/high-resolution mass spectrometer. Recoveries of OCPs spiked to actual samples such as rainwater, river water and seawater samples were approximately more than 80%, and the coefficients of variations were within 10%. This method was applied to the actual samples and was confirmed to be applicable for monitoring sub-ng/l level OCPs in environmental water samples.

Charcoal↗

Three sample preparation protocols for polymerase chain reaction based detection of Cryptosporidium parvum in environmental samples.

Cryptosporidium parvum is a protozoan parasite responsible for an increasing number of outbreaks of gastrointestinal illness worldwide. In this report, we describe development of sample preparation protocols for polymerase chain reaction (PCR)-based detection of C. parvum in fecal material and environmental water samples. Two of these methods were found adequate for isolation of Cryptosporidium DNA from filtered water pellet suspensions. The first involved several filtration steps, immunomagnetic separation and freeze-thaw cycles. The second method involved filtration, addition of EnviroAmp lysis reagent, freeze-thaw cycles and precipitation of the DNA with isopropanol. Using nested PCR, we detected 100 oocysts/ml of filtered water pellet suspension, with either of the above sample preparation procedures. Nested PCR increased sensitivity of the assay by two to three orders of magnitude as compared to the primary PCR. The detection limit for seeded fecal samples was 10-fold higher than for filtered environmental water pellet suspension. Nested PCR results showed 62.4 and 91.1% correlation with immunofluorescence assay (IFA) for fecal samples and filtered environmental water pellet suspensions, respectively. This correlation decreased to 47.2% and 44.4%, respectively, when only IFA positive samples were analyzed. However, in fecal samples contaminated with a high number (> 10(5)/g) of C. parvum oocysts, this correlation was 100%.

2-Propanol↗

Analysis of multiple samples using multiplex sample NMR: selective excitation and chemical shift imaging approaches.

Two improved approaches for the rapid analysis of multiple samples using multiplex sample NMR are described. In the first approach, frequency-selective 90 degrees radio frequency pulses and large pulsed field gradients are applied to excite and detect multiple samples in rapid succession. This method is advantageous for samples with relatively long longitudinal (T1) relaxation times. In the second approach, chemical shift imaging is applied to acquire both the spectral and spatial information of multiple samples simultaneously. Chemical shift imaging is more time-consuming than selective excitation; however, it is advantageous for detecting samples with short T1's and for signal averaging. Both approaches demonstrate the potential of multiplex sample NMR for carrying out high-throughput NMR detection.

Journal Article↗

Membrane extraction with a sorbent interface for headspace monitoring of aqueous samples using a cap sampling device

A cap-shaped device was employed for headspace sampling. This sampling device coupled to membrane extraction with a sorbent interface (MESI) is intended to perform on-site and on-line aqueous sample monitoring. A laboratory sampling testwas performed both at the water surface and under water, and it showed some advantages in underwater monitoring. A group of volatile organic compounds (VOCs), varying in PDMS/gas and gas/water distribution constants, benzene, toluene, ethylbenzene, o-xylene, and trichloroethylene (TCE), was used for the sampling study. Magnetic stirring of the sample and circulation of the headspace air with a microfan were used for the enhancement of mass transfer between sample matrix and membrane to obtain higher extraction rate and efficiency. The agitation approaches were investigated individually and compared. The results showed that simultaneous agitation in water and air could greatly improve the extraction efficiency. Good linearity and precision and low detection limits were obtained for water-surface monitoring. The study demonstrated that Cap-MESI is a useful tool for field headspace monitoring of volatile organic compounds.

Journal Article↗