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PubMed2002

Surface sampling methods for Bacillus anthracis spore contamination.

During an investigation conducted December 17-20, 2001, we collected environmental samples from a U.S. postal facility in Washington, D.C., known to be extensively contaminated with Bacillus anthracis spores. Because methods for collecting and analyzing B. anthracis spores have not yet been validated, our objective was to compare the relative effectiveness of sampling methods used for collecting spores from contaminated surfaces. Comparison of wipe, wet and dry swab, and HEPA vacuum sock samples on nonporous surfaces indicated good agreement between results with HEPA vacuum and wipe samples. However, results from HEPA vacuum sock and wipe samples agreed poorly with the swab samples. Dry swabs failed to detect spores >75% of the time when they were detected by wipe and HEPA vacuum samples. Wipe samples collected after HEPA vacuum samples and HEPA vacuum samples collected after wipe samples indicated that neither method completely removed spores from the sampled surfaces.

Bacillus anthracis↗
PubMed2000

Microbiological sampling of carcasses by excision or swabbing.

Groups of 25 carcasses were obtained by random selection of carcasses at the end of each of eight commercial processes for the dressing or cooling of carcasses. Samples were collected from six groups of pig or beef carcasses by excision or swabbing with sponge, gauze, or cotton wool, with one sample obtained by each of the four methods from a separate, randomly selected site on each carcass. Total aerobic counts, coliforms, and Escherichia coli from each sample were enumerated. Values for the mean log10, log10 mean, and log10 total numbers recovered were calculated for each set of total aerobic counts. Those statistics indicated that the numbers of bacteria recovered by excision or swabbing with sponge or gauze were similar, while the numbers recovered by swabbing with cotton wool were at the lower end of or below the range of the numbers recovered by the other methods. The numbers of coliforms or E. coli recovered from carcasses by sampling areas up to 100 cm2 were too few for the estimation of log mean numbers. Sampling of two groups of carcasses by swabbing with gauze indicated that each 10-fold increase in the area sampled, from 10 to 1,000 cm2, approximately doubled the number of samples from which coliforms or E. coli were recovered. Sampling of six groups of carcasses from one process indicated that the sizes of swabs and volumes of diluent used for processing swabs did not have to be increased proportionally to the area of carcass surface sampled to recover numbers of E. coli proportional to the sampled area. It therefore appears that carcass sampling techniques can be varied widely without compromising the recovery of bacteria, and that the relative efficiencies with which bacteria are recovered by different techniques can be assessed by sampling each carcass in a group of 25 by each of the methods to be compared.

Animals↗
PubMed1999

Comparison of fecal samples collected per rectum and off the ground for estimation of environmental contamination attributable to beef cattle.

OBJECTIVES: To determine whether sampling feces off the ground replicates prevalence estimates for specific pathogens obtained from fecal samples collected per rectum of adult cows, and to determine characteristics of feces on the ground (fecal pats) that are associated with subsequent identification of Campylobacter spp, Cryptosporidium parvum, and Giardia duodenalis. ANIMALS: A random sample of adult beef cattle from 25 herds located throughout California. PROCEDURE: 1,115 rectal and ground fecal samples were obtained. Samples were submitted for culture of Campylobacter spp and examined, using a direct fluorescent antibody assay, to detect C parvum oocysts and G duodenalis cysts. Characteristics of fecal pats, such as volume and consistency, were recorded. RESULTS: Prevalence of Campylobacter spp was 5.0% (20/401) for rectal fecal samples, which was significantly greater than prevalence determined for ground fecal samples (2/402; 0.5%). Most isolates were C jejuni subsp jejuni. Prevalence of C parvum was higher in rectal fecal samples (6/557; 1.1%) than in ground fecal samples (1/558; 0.2%), but this difference was not significant. Prevalence of G duodenalis did not differ for rectal (36/557; 6.5%) versus ground (26/558; 4.7%) fecal samples. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation of ground fecal samples may not accurately indicate the prevalence of Campylobacter spp or C parvum in cattle but may reflect prevalence of G duodenalis. Differences in prevalence estimates between the 2 methods suggest inactivation of pathogens in feces after cattle have defecated. Prevalence estimates generated by evaluation of ground fecal samples, however, may more accurately estimate environmental pathogen burden.

Animals↗
PubMedDate not supplied

Intratumoral heterogeneity in colorectal carcinoma: trucut sampling for DNA ploidy analysis.

BACKGROUND: Solid tumors, such as colorectal carcinomas, consist of cell subpopulations that differ both genetically and in their clinical behavior. Many authors have examined cell kinetics and DNA content in colorectal tumors in correlation to clinical and pathological variables with different results. The interpretation of those results present some difficulties related to tumor heterogeneity that to date are unsolved. Our study is based on a new method of colon cancer sampling for DNA content determination. The aim of this work was to reduce the risk of incorrect DNA evaluation due to tumor heterogeneity. MATERIAL AND METHODS: Our study was based on eleven selected cases of T3 colorectal carcinoma. Fresh surgical specimens from the primary tumor site were taken during surgery. For each case at least four samples were taken using a 23 gauge trucut from the outside of the serosa through the tumor to the lumen of the colon. The specimens were stained according to a modified Feulgen method and DNA content was measured by image analysis. Three parameters were evaluated: DNA index, ploidy and proliferation level (considered as the sum of elements corresponding to the S and G2 phases). RESULTS: One of the eleven (9.1%) tumors showed a diploid pattern; four out of eleven (36.4%) cases showed a tetra/polyploid pattern and six out of eleven (54.5%) cases showed an aneuploid pattern. Three tumors were monoclonal (27.3%), one diploid and two aneuploid. Eight were polyclonal (72.7%). Considering the single specimen, seven out of sixty-eight specimens (10.3%) were inadequate because of scanty material. Twenty-five out of the sixty-one adequate specimens (41%) were monoclonal and thirty-six (59%) were polyclonal. Five tumors (three monoclonal and two polyclonal) showed the same cell clones on all the examined samples. The remaining six tumors showed interregional variability. The six of the eight polyclonal cases (75%) multiple stem lines were evident, analyzing only one sample taken close to colon serosa, while in one case (25%) it was necessary to examine two samples in order to see the polyclonality of the lesion. When samples taken close to mucosa where analyzed, however, one sample was not enough to show tumor polyclonality in five of the eight polyclonal examined cases. Proliferation level varied greatly in different parts of the same carcinoma and did not correlate to the site from which the sample was taken. CONCLUSION: In the present study, we demonstrated that DNA ploidy differences may exist between the superficial and the deep part of the same neoplasia and that tumor samples show a greater variability in the deeper layers. Using trucut samplings, it was possible to point out the majority of aneuploid cell populations close to the serosa. In conclusion, trucut biopsy permits full thickness sampling of the tumoral mass and allows, from few samples, to evaluate the multiple DNA stemlines present in different parts of a colorectal tumor.

Aged↗
PubMed2002

Comparison of five point-of-care prothrombin and activated partial thromboplastin time devices based on age of blood sample.

Delays in processing statium (STAT) blood samples have led to the production of an increasing number of point-of-care tests. Product inserts recommend measuring blood samples immediately after procurement, suggesting that delays may invalidate the test results. We studied the effect of the age of blood samples on point-of-care (POC) prothrombin time (PT) and an activated partial thromboplastin time (aPTT) result. Informed consent was obtained from 11 patients undergoing cardiopulmonary bypass (CPB). Blood samples (40 mL) were taken from each patient. Each blood sample was used to perform five PT tests and six aPTT tests on five POC devices (Gem PCL, Hemochron 801, Hemochron Jr. Signature, Hemochron Response, Rapidpoint Coag) at three different sample ages [< 60 s (fresh blood), 10 and 18 min after sample collection]. Blood samples were procured in a plastic syringe devoid of air bubbles, which was left undisturbed between tests but was gently agitated before initiating the 10- and 18-min tests. For tests requiring citrated whole blood, a fraction of each sample was anticoagulated (3.8% citrate) at each age. Statistical analysis was used for comparison of test results for fresh blood to aged samples (10 and 18 min). Test values were recorded as International Normalized Ratio (INR) and seconds for PT and aPTT, respectively. Two devices, the Hemochron 801 and Hemochron response showed statistically, although not clinically, significant variation in PT test results when the samples were aged to 10 and 18 minutes. As for aPTT results, Hemochron 801, Hemochron response, Hemochron Jr. signature, and Gem PCL showed statistically significant variation at 18 minutes. One device (Hemochron 801) reported results with 10-min aged blood that were statistically different from fresh blood. None of the aPTT tests results from any device produced results with aged blood that were clinically different from fresh blood. This study suggests that, in the tests evaluated, blood samples that have aged 10 or 18 min will produce clinically relevant aPTT and PT results, respectively.

Adult↗
PubMed2003

Dried venous blood samples for the detection and quantification of measles IgG using a commercial enzyme immunoassay.

OBJECTIVES: To determine whether samples of dried venous blood (DVB) were an acceptable alternative to serum for detecting measles-specific IgG in a commercial enzyme immunoassay. METHODS: Paired samples of serum and DVB were collected from 98 suspected cases of measles and 1153 schoolchildren in Victoria, Australia. All samples were tested using the Dade Behring Enzygnost Anti-Measles-Virus/IgG immunoassay. DVB samples were eluted using either the sample buffer provided with the kit or 5% dry milk powder in phosphate-buffered saline-Tween 20. FINDINGS: DVB samples eluted by sample buffer showed significantly better linear correlation to the serum samples than did DVB samples eluted in 5% dry milk in phosphate-buffered saline-Tween 20. To improve the comparability of serum and DVB samples an adjustment factor of 1.28 was applied to the optical density (OD) values of DVB. This adjustment also enabled quantification of the titre of measles IgG in mIU/ml directly from the OD value using the alpha calculation as specified by the kit protocol. For DVB samples stored for less than six months at 4 degrees C, the assay showed an overall sensitivity of 98.4% and a specificity of 97.2% compared with the results of serum testing. CONCLUSION: These results illustrate the potential for DVB samples to be widely used with the Dade Behring enzyme immunoassay system for determining the immunity of the individual and the population to the measles virus.

Adolescent↗
PubMed2005

A new design of groundwater sampling device and its application.

Compounds in the atmosphere contaminate samples of groundwater. An inexpensive and simple method for collecting groundwater samples is developed to prevent contamination when the background concentration of contaminants is high. This new design of groundwater sampling device involves a glass sampling bottle with a Teflon-lined valve at each end. A cleaned and dried sampling bottle was connected to a low flow-rate peristaltic pump with Teflon tubing and was filled with water. No headspace volume was remained in the sampling bottle. The sample bottle was then packed in a PVC bag to prevent the target component from infiltrating into the water sample through the valves. In this study, groundwater was sampled at six wells using both the conventional method and the improved method. The analysis of trichlorofluoromethane (CFC-11) concentrations at these six wells indicates that all the groundwater samples obtained by the conventional sampling method were contaminated by CFC-11 from the atmosphere. The improved sampling method greatly eliminated the problems of contamination, preservation and quantitative analysis of natural water.

Chlorofluorocarbons, Methane↗
PubMedDate not supplied

Parameters for determining the origin of illicit heroin samples.

A method has been evolved for assigning the source of supply or origin of illicit heroin samples. The content of morphine, codeine and acetyl products and the ratios of morphine to codeine and heroin to acetylcodeine obtained from opium samples of known origin as well as the content of heroin (diacetylmorphine) and acetylcodeine and their ratios in illicit heroin samples that have been found to belong to the same source of supply as the known opium samples are used as the basic criteria for a comparison to determine the origin of illicit heroin samples. Because the content of alkaloids in opium and heroin samples varies considerably, the number of opium and illicit heroin samples of known origin analysed should be sufficient to determine a representative composition of alkaloids in such samples for a given geographical area and period of production. It was observed that the theoretical ratio of heroin to acetylcodeine increases two-fold at each stage of the chemical conversion in the series opium-morphine-heroin. The ratios of heroin to acetylcodeine obtained from opium samples of known origin showed significant variation, which enabled the author to make distinct composition profiles of the alkaloids for each geographical area studied. Such profiles made it possible to compare heroin samples of known origin with illicit heroin samples of unknown origin and to determine the geographical area from which the latter originated. This method can also be applied in determining the origin of illicit morphine samples.

Chemical Phenomena↗
PubMed1984

Appropriateness of sampling times for therapeutic drug monitoring.

Serum sampling for drug concentration was evaluated for usefulness in pharmacokinetic calculations and dosage adjustment. The prospective study included serum samples for 11 drugs in hospital inpatients during a four-week period. Appropriateness of sampling regarding (1) time of drug administration and (2) steady state was determined. Both of these evaluations were used in the final rankings of appropriateness of the samples with regard to ease of interpretation and clinical usefulness. Digoxin, theophylline, tobramycin, and phenytoin accounted for 81% of the 466 samples evaluated. Sampling time was recorded for 56% of all samples. Based on time of dose administration, 54% of samples were obtained at the recommended time; 38% of samples were obtained at steady state. Basic pharmacokinetic methods could be used to interpret 15% of samples, while 44% required complex pharmacokinetic methods, 34% required assumptions about sampling time versus dosing history, and 7% should not have been used in dosage adjustment. The majority of plasma drug samples required more than basic pharmacokinetic methods for evaluation. For assessment of therapeutic drug regimens by monitoring serum drug concentrations, sophisticated pharmacokinetic consultation services are needed.

Blood Specimen Collection↗
PubMed1995

Flow cytometric DNA analysis of ulcerative colitis using paraffin-embedded biopsy specimens: comparison with morphology and DNA analysis of fresh samples.

OBJECTIVES: The detection of aneuploidy in colonic mucosa by flow cytometric DNA analysis has been advocated as an indicator of high risk for ulcerative colitis (UC) patients developing colon carcinoma. To date, studies have primarily utilized fresh tissue and have had two limitations: a significant number of possible false-positive findings (aneuploidy in the absence of detectable dysplasia) that may be due to DNA degradation, and the inherent inability to perform retrospective studies. The latter has compromised the adequate assessment of flow cytometric DNA analysis for its clinical utility in UC patients. Our objective was to attempt to overcome the limitations that have been present in DNA analysis by flow cytometry. METHODS: After having established, in our laboratory, an optimal method that allowed reliable DNA analysis on paraffin-embedded mucosal biopsy specimens, we conducted three separate studies to address the above problems associated with DNA analysis with fresh colonic samples: 1) comparison of DNA analysis between fresh and paraffin-embedded colonic mucosal samples from UC patients without dysplasia, 2) correlation between morphology and DNA ploidy on paraffin-embedded tissues showing no dysplasia and various degrees of dysplasia, and 3) sequential analysis of fresh, normal colonic mucosal samples to further evaluate possible causes of false aneuploidy. RESULTS: We observed 1) that there is discordance in DNA ploidy between paraffin-embedded and fresh samples showing no dysplasia in that aneuploidy was found in 33/46 (72%) of fresh samples, whereas 3/40 (7.5%) were aneuploid by biopsies from the corresponding anatomic sites. 2) There is excellent correlation between dysplasia and DNA ploidy results with paraffin-embedded tissue, i.e., none of 16 samples negative for dysplasia, none of seven samples indefinite for dysplasia, and seven of eight samples positive for dysplasia were aneuploid. 3) DNA degradation produced a spurious, near-diploid aneuploid peak in a normal colonic mucosal sample when it was left in saline more than 1 hr before analysis. CONCLUSIONS: The above-described results demonstrate that performing flow cytometric DNA analysis with formalin-fixed paraffin-embedded biopsy samples is feasible and that this technique may provide more reliable ploidy results than does the use of fresh samples, when rapid refrigeration and/or freezing of the fresh samples cannot be accomplished consistently, and will permit retrospective DNA ploidy studies assessing risk of cancer in UC patients.

Adult↗
PubMed1994

Effect of sample handling on measurement of plasma glucose and blood lactate concentrations in horses before and after exercise.

Collection of a satisfactory blood sample requires special procedures to prevent changes in glucose and lactate content after the sample has been obtained. Changes in measured plasma glucose and blood lactate concentrations attributable to anticoagulants and storage procedures, respectively, were examined in blood samples obtained from horses at rest and after exercise. To evaluate the effect of anticoagulants on measured plasma glucose concentration, blood was preserved with either sodium fluoride/potassium oxalate or lithium heparin. Measured plasma glucose concentration in blood obtained at rest and after exercise was 6 and 10% lower (P = 0.0038), respectively, when blood was preserved with fluoride/oxalate, compared with heparin. The erythrocyte volume in the blood sample was 15% smaller (P = 0.0001) in samples preserved with fluoride/oxalate, indicating a movement of water out of erythrocytes in the blood sample mixed with that anticoagulant. To evaluate the effect of storage procedure on measured blood lactate concentration, part of the blood sample was immediately deproteinized for blood lactate analysis, and the remaining blood was maintained for 30 and 60 minutes at either 0 or 22 C before deproteinization. When blood samples were maintained at 0 C prior to deproteinization, there was no difference in blood lactate concentration, regardless of the incubation time, compared with that in samples immediately deproteinized. Blood lactate concentration was greater (P < 0.01) in samples maintained at 22 C, compared with that in samples immediately deproteinized, and with that in equivalent samples maintained at 0 C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[An oral-ruminal probe for rumen sampling in the adult sheep].

Ten adult (height: 63-85 cm) rumen-fistulated sheep were used to test the usefulness of an ororuminal probe and a suction pump for the acquisition of ruminal fluid. The use of these instruments in 50 samplings rendered 200 ml of ruminal fluid each time. The introduction of the probe took 18 +/- 6.5 s, whereby the probe was inserted to a length of 91.3 +/- 3.5 cm. The collection of 200 ml of ruminal fluid took 7.4 +/- 2.2 s. The sampling location was the ventral ruminal sack. By comparing the fluid taken by the ororuminal probe with samples taken via ruminal fistula by a tube-like probe no significant differences in regard to pH, total acidity, reduction potential, ammonia, acetate, L-lactate, sodium and chloride concentrations were found. However, significant differences between ororuminal probe samples and fistula samples were observed in regards to the concentrations of total volatile fatty acids, propionate, n-butyrate, i-butyrate, n-valeriate, i-valeriate, calcium, phosphate, magnesium and potassium. The differences were independent of the sampling order (ororuminal probe prior to fistula and vice versa). These results indicate that samples taken by the ororuminal probe do not contain sampling-dependent saliva residues. Those samples collected via fistula had consistently higher concentrations of total volatile fatty acids, propionate, n-butyrate, i-butyrate, n-valeriate, and i-valeriate, as well as higher concentrations of calcium, phosphate, magnesium and potassium than samples taken with the ororuminal probe. These results indicate that samples taken via fistula originated from more dorsal regions than the samples taken by ororuminal probe from the ventral ruminal sack. The ororuminal probe and the suction pump used proved to be useful for the collection of ruminal fluid from the ventral ruminal sack in adult sheep (height: 63-85 cm).

Animals↗
PubMed1998

Polymerase chain reaction analysis of corneal epithelial and tear samples in the diagnosis of Acanthamoeba keratitis.

PURPOSE: Acanthamoeba is an uncommon cause of corneal infection in which the best visual outcome follows prompt diagnosis and a long course of appropriate antimicrobial therapy. Because conventional detection techniques for Acanthamoeba have certain limitations, we investigated the ability of the polymerase chain reaction (PCR) to confirm the clinical diagnosis of Acanthamoeba keratitis, with the ultimate aim of achieving early diagnosis. METHODS: Using two different pairs of primers, PCR was performed on representative cultured Acanthamoeba isolates to confirm the assay's ability to amplify Acanthamoeba DNA from a wide range of acanthamoebae. Subsequently, corneal epithelial samples from 19 patients and tear samples from 12 patients with Acanthamoeba keratitis were analyzed by PCR for the presence of Acanthamoeba DNA. RESULTS: Acanthamoeba DNA was amplified by PCR from 16 (84%) of 19 corneal epithelial samples, whereas Acanthamoeba was cultured from 10 samples (53%), all of which were PCR positive. Tear samples from 8 (66%) of 12 patients were positive on PCR testing, and one tear sample was PCR positive, whereas the corresponding epithelial biopsy had yielded a negative PCR result. Samples from culture-positive patients were positive on PCR testing more frequently than those from culture-negative patients (10/10 culture-positive corneal epithelial and 5/7 [71%] culture-positive initial tear samples versus 6/9 [66%] culture-negative corneal epithelial and 2/5 [40%] culture-negative tear samples). All control epithelial (n = 15) and tear (n = 15) samples yielded negative results. CONCLUSIONS: PCR was a more sensitive diagnostic test than a culture for Acanthamoeba keratitis, and the use of two different primers achieved better sensitivity than a single set. A PCR of a tear sample also may be a useful complementary test and, in combination with PCR of epithelial samples, would prove particularly helpful in confirming the clinical diagnosis in culture-negative cases.

Acanthamoeba↗
PubMed1996

Comparison of some practical sampling strategies for population pharmacokinetic studies.

Using population analysis, sparsely sampled Phase 3 clinical data can be utilized to determine the pharmacokinetic characteristics of the target population. Data arising from such studies are likely to be constrained to certain sampling windows, i.e., the visiting hours at the study clinic. When the sampling window is narrow compared to the half-life of the drug, the advantage of taking more than one sample is not obvious. Study designs with one or two samples per visit have been compared with respect to (i) precision and bias of the population parameter estimates, (ii) the ability to identify the underlying pharmacokinetic model, and (iii) the estimation of individual parameter values. The first point was assessed using simulated data while the latter two were studied using a real data set. Results show: (i) Parameter estimates are more biased and imprecise when only one sample is taken compared to when two samples are obtained, this is true irrespective of the time span between the two samples. (ii) Ability to identify a more complex model is increased if two samples are taken. Specifically, the variability between occasions can be quantified. (iii) Two-sample designs are generally better with respect to prediction of individual parameter values. Even minor changes to commonly employed study designs, in this case the addition of one sample at each study occasion, can improve quality and quantity of the information obtained.

Computer Simulation↗
PubMed2002

Accuracy of plasma sample methods for determination of glomerular filtration rate with 99mTc-DTPA.

UNLABELLED: The plasma sample method following a single injection of radioactive markers has been proved to be simple and accurate for the determination of glomerular filtration rate (GFR) in clinical practice. The aim of this study was to assess clinical accuracy of single-, two- and multi-sample methods. METHODS: The study was performed on 50 patients with various degrees of renal dysfunction (29 males and 21 females; aged 27 to 90 years). As a reference the true GFR (GFRt) was determined by means of the two-compartment model curve fitting 10 plasma samples following a single-injection of 99mTc-DTPA. The GFRt was compared to the GFR estimated by the Christensen and Groth's single-sample (GFRcg), two-sample (GFR2s) and multi-sample (GFRm) between 75 and 300 min after the injection. The GFRs by two- and multi-sample methods were determined with the slope and intercept algorithm and its overestimation was corrected by Brochner-Mortensen's formula. RESULTS: In 49 patients with GFR between 12 and 169 ml/min/1.73 m2, the standard deviation of difference (95% limits of agreement) between GFRt and GFRcg at 180 min was 6.513 ml/min/l73 m2 (-16.5 approximately 9.5 ml/min/1.73 m2), which was somewhat closer than 7.311 ml/min/1.73 m2 (-12.5 approximately 16.5 ml/min/1.73 m2) in GFR2s in slow clearance phase at 120 min and 240 min. However, the single-sample method tended to show some scattering in GFR below 30 and above 140 ml/min/ 1.73 m2. On the contrary, the 2-sample method tended to be scattered in GFR above 120 ml/min/ 1.73 m2. CONCLUSION: In view of its accuracy and technical simplicity, the single-sample method is first choice in a routine practice. The two-sample method is essential of choice for a patient in whom the GFR is expected to be below 30 ml/min/1.73 mi2. These two methods may be chosen selectively in dependence on the preserved renal function which is expected at time of the test.

Adult↗
PubMed1998

Assessing the feasibility of recruiting a randomly selected sample of psychiatrists to participate in a national practice-based research network.

This study tested the feasibility of recruiting and retaining a randomly selected sample of psychiatrists compared to a volunteer sample to participate in the American Psychiatric Association's Practice Research Network (PRN). One hundred-forty psychiatrists were randomly selected and contacted by phone by peer psychiatrists for recruitment into the PRN. As a comparison group, a sample of 146 self-selected volunteer psychiatrists were also included in the study. Recruited and volunteer psychiatrists were asked to participate in three studies to assess study compliance and retention. The representativeness of each sample was evaluated by comparing the psychiatrists' sociodemographic and practice characteristics to existing national data on psychiatrists. Study response rates and long-term retention rates were compared for the two groups. Sixty-one percent of the recruited sample who were eligible to participate in the network were willing to participate. Both the recruited and volunteer samples were broadly representative of the American Psychiatric Association's membership (with some differences in race, ethnicity and board certification). Of the recruited sample, 74.5% (38/51) successfully completed the network's first three pilot studies compared to 72.5% (98/135) of the volunteer sample. No psychiatrists in the recruited sample withdrew from the network compared to 2.1% (3/138) of the volunteer sample. These findings indicate a randomly selected sample of psychiatrists can be recruited and retained to participate in practice-based research. These methods can be used to enhance the generalizability of observational health services research studies, which require the participation of practicing clinicians. More effective methods should be tested to enhance participation rates.

Feasibility Studies↗
PubMed2006

Sampling scale effects in random fields and implications for environmental monitoring.

The concept of a sampling scale triplet of spacing, extent and support is used to define the spatial dimensions of a monitoring network or a field study. The spacing is the average distance between samples, the extent is the size of the domain sampled and the support is the averaging area of one sample. The aim of this paper is to examine what is the bias and the random error (uncertainty) introduced by the sampling scale triplet into estimates of the mean, the spatial variance and the integral scale of a variable in a landscape. The integral scale is a measure of the average distance over which a variable is correlated in space. A large number of two dimensional random fields are generated from which hypothetical samples, conforming to a certain sampling scale triplet, are drawn which in turn are used to estimate the sample mean, spatial variance and integral scale. The results indicate that the biases can be up to two orders of magnitude. The bias of the integral scale is positively related to the magnitude of any of the components of the scale triplet while the bias of the spatial variance is different for different components of the scale triplet. All sampling scale effects are relative to the underlying correlation length of the variable of interest which is closely related to the integral scale. The integral scale can hence be used for sampling design and data interpretation. Suggestions are given on how to adjust a monitoring network to the scales of the variables of interest and how to interpret sampling scale effects in environmental data.

Data Collection↗
PubMed2005

Sample size computations for PK/PD population models.

We describe an accurate, yet simple and fast sample size computation method for hypothesis testing in population PK/PD studies. We use a first order approximation to the nonlinear mixed effects model and chi-square distributed Wald statistic to compute the minimum sample size to achieve given degree of power in rejecting a null hypothesis in population PK/PD studies. The method is an extension of Rochon's sample size computation method for repeated measurement experiments. We compute sample sizes for PK and PK/PD models with different conditions, and use Monte Carlo simulation to show that the computed sample size retrieves the required power. We also show the effect of different sampling strategies, such as minimal, i.e., as many observations per individual as parameters in the model, and intensive on sample size. The proposed sample size computation method can produce estimates of minimum sample size to achieve the desired power in hypothesis testing in a greatly reduced time than currently available simulation-based methods. The method is rapid and efficient for sample size computation in population PK/PD study using nonlinear mixed effect models. The method is general and can accommodate any type of hierarchical models. Simulation results suggest that intensive sampling allows the reduction of the number of patients enrolled in a clinical study.

Algorithms↗