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PubMed2006

Automation of sample mounting for macromolecular crystallography.

A standard sample holder and vial for cryocooled macromolecular crystals has been defined for use with robotic sample changers. This SPINE standard sample holder is a modified version, with added features and specifications, of sample holders in common use. In particular, the SPINE standard meets the precision required for automatic sample exchange and includes a cap that is identified by a two-dimensional datamatrix code as well as an optional vial. At the ESRF, the sample holder standard is in use with the EMBL/ESRF/BM14 robotic sample changer (SC3) which is installed on eight beamlines. The SC3 can hold up to 50 crystals stored in five baskets. A datamatrix reader in the SC3 ensures safe management of the sample flow and facilitates fully automatic screening and characterization of samples. Tools for handling and transporting 50 samples in a dry shipping dewar have been developed. In addition to the SC3, the SPINE sample holder is currently compatible with a number of other robotic sample changers.

Automation↗
PubMed1995

Detection of Yersinia enterocolitica O:3 in faecal samples and tonsil swabs from pigs using IMS and PCR.

Dilutions of faecal samples spiked with Yersinia enterocolitica O:3 were analysed using immunomagnetic separation (IMS) followed by PCR. In 10% faecal dilutions with added Y. enterocolitica cells, the limit of detection was 200 cells g-1 faeces. Faecal samples from 38 pigs were analysed by IMS-PCR in parallel with detection and quantification of Y. enterocolitica O:3 using cold pre-enrichment culturing. Of the 15 culture-positive samples, only two were detected with IMS-PCR. These two samples contained 40-400 Y. enterocolitica O:3 cells g-1 faeces; the highest level found in the investigation. This indicated that the low sensitivity of IMS-PCR was due to low amounts of cells in the faecal samples. Swab samples from 195 pig tonsils, taken on a slaughterline were examined using IMS-PCR and culture detection. Of 164 culture-positive samples, 60 were positive with IMS-PCR. In addition, IMS-PCR was positive for three culture-negative samples. Forty-five of the samples were further examined by IMS-PCR after 7-10 d of cold pre-enrichment. All 31 culture-positive samples as well as five culture-negative samples were detected by IMS-PCR. From these data it can be concluded that IMS-PCR can be used to detect Y. enterocolitica O:3 cells after pre-enrichment, but direct detection needs further optimization of the sample preparation procedures.

Animals↗
PubMed1984

The transverse strength of acrylic resin strips and of repaired acrylic samples.

A method was developed for measuring the transverse strength of repaired acrylic samples at a single butt joint. The strength was determined for samples prepared from two types of heat polymerizing resins and two types of repair resins. The temperature elevation during curing of the repair resins was determined. Cross-linking of the resins was evaluated by immersion of samples in solvents. The appearance of the bead microstructure after various treatments was considered to indicate relaxation at the sample surface. Repaired samples of the heat polymerizing resin which exhibited relaxation after immersion in monomer, had a lower strength than samples prepared from the resin for which relaxation was not observed, although both resins were cross-linked to a similar extent. The application of pressure during curing increased the strength of the samples repaired with the rapid curing, cross-linked, repair resin. The strength of the samples repaired with the uncross-linked, slow curing, repair resin was affected by pressure only if the insertion of the repair resin between the sample parts was delayed after mixing. Variations in the powder to liquid ratio of the uncross-linked repair resin did not affect the sample strength. Wetting of the sample parts with monomer before repair, and variations in the curing temperature did not affect the sample strength for the investigated resin combinations.

Acrylic Resins↗
PubMed2006

Comparison of bacterial plaque samples from titanium implant and tooth surfaces by different methods.

Studies have shown similarities in the microflora between titanium implants or tooth sites when samples are taken by gingival crevicular fluid (GCF) sampling methods. The purpose of the present study was to study the microflora from curette and GCF samples using the checkerboard DNA-DNA hybridization method to assess the microflora of patients who had at least one oral osseo-integrated implant and who were otherwise dentate. Plaque samples were taken from tooth/implant surfaces and from sulcular gingival surfaces with curettes, and from gingival fluid using filter papers. A total of 28 subjects (11 females) were enrolled in the study. The mean age of the subjects was 64.1 years (SD+/-4.7). On average, the implants studied had been in function for 3.7 years (SD+/-2.9). The proportion of Streptococcus oralis (P<0.02) and Fusobacterium periodonticum (P<0.02) was significantly higher at tooth sites (curette samples). The GCF samples yielded higher proportions for 28/40 species studies (P-values varying between 0.05 and 0.001). The proportions of Tannerella forsythia (T. forsythensis), and Treponema denticola were both higher in GCF samples (P<0.02 and P<0.05, respectively) than in curette samples (implant sites). The microbial composition in gingival fluid from samples taken at implant sites differed partly from that of curette samples taken from implant surfaces or from sulcular soft tissues, providing higher counts for most bacteria studied at implant surfaces, but with the exception of Porphyromonas gingivalis. A combination of GCF and curette sampling methods might be the most representative sample method.

Bacteroides↗
PubMed1999

Detection of infectious Cryptosporidium parvum oocysts in surface and filter backwash water samples by immunomagnetic separation and integrated cell culture-PCR.

A new strategy for the detection of infectious Cryptosporidium parvum oocysts in water samples, which combines immunomagnetic separation (IMS) for recovery of oocysts with in vitro cell culturing and PCR (CC-PCR), was field tested with a total of 122 raw source water samples and 121 filter backwash water grab samples obtained from 25 sites in the United States. In addition, samples were processed by Percoll-sucrose flotation and oocysts were detected by an immunofluorescence assay (IFA) as a baseline method. Samples of different water quality were seeded with viable C. parvum to evaluate oocyst recovery efficiencies and the performance of the CC-PCR protocol. Mean method oocyst recoveries, including concentration of seeded 10-liter samples, from raw water were 26.1% for IMS and 16.6% for flotation, while recoveries from seeded filter backwash water were 9.1 and 5.8%, respectively. There was full agreement between IFA oocyst counts of IMS-purified seeded samples and CC-PCR results. In natural samples, CC-PCR detected infectious C. parvum in 4.9% (6) of the raw water samples and 7.4% (9) of the filter backwash water samples, while IFA detected oocysts in 13.1% (16) of the raw water samples and 5.8% (7) of the filter backwash water samples. All CC-PCR products were confirmed by cloning and DNA sequence analysis and were greater than 98% homologous to the C. parvum KSU-1 hsp70 gene product. DNA sequence analysis also revealed reproducible nucleotide substitutions among the hsp70 fragments, suggesting that several different strains of infectious C. parvum were detected.

Animals↗
PubMed2003

Group A rotavirus in sewage samples from Barcelona and Cairo: emergence of unusual genotypes.

The presence of rotavirus strains in sewage samples from Cairo, Egypt (November 1998 to October 1999), and Barcelona, Spain (November 1998 to December 2002), was investigated by using a generic molecular detection method based on amplification of a VP6 gene fragment. Overall, 85.7 and 66.9% of the sewage samples from Cairo and Barcelona, respectively, were positive. Positive samples were characterized further, and VP7 and VP4 genotypes were determined. Although 30% of the positive samples from Cairo were G untypeable, the distribution of G types in the positive samples was 69.6% G1, 13% G3, 8.7% G4, and 8.7% G9. The percentage of untypeable samples was much higher for the Barcelona samples (56.5%), and the distribution in the positive samples was 56.4% G1, 31.5% G3, 6% G9, 4% G2, and 2% G5. When the P types were examined, 26.7% of the positive samples from Cairo were untypeable, and the distribution of types in the positive samples was 53.3% P[8], 30% P[6], and 16.6% P[4]. In Barcelona, 27.2% of the samples were P untypeable, and the frequencies of the types detected were 49.7% P[8], 37.2% P[4], 8.8% P[6], and 4.2% P[9]. The distribution for strains from Cairo was 38.5% P[8]G1, 27% P[6]G1, 11.5% P[4]G1, 11.5% P[8]G3, 7.7% P[6]G4, and 3.8% P[8]G9. Strikingly, equivalent frequencies of common and uncommon strains were observed for Barcelona samples, and the distribution was 38.8% P[8]G1, 30.6% P[4]G1, 11.6% P[8]G3, 6.6% P[4]G3, 5.8% P[6]G1, 1.6% P[6]G3, 1.6% P[9]G1, 0.8% P[4]G2, 0.8% P[6]G9, 0.8% P[8]G9, and 0.8% P[8]G5. Additionally, two P[-]G5 strains were isolated in Barcelona, and the porcine or human origin of these strains was unclear. Rotavirus variability exhibited not only a geographic pattern but also a temporal pattern.

Antigens, Viral↗
PubMed2000

Use of a dry-plasma collection device to overcome problems with storage and transportation of blood samples for epidemiology studies in developing countries.

Studies are difficult in areas lacking modern facilities due to the inability to reliably collect, store, and ship samples. Thus, we sought to evaluate the use of a dry plasma collection device for seroepidemiology studies. Plasma was obtained by fingerstick using a commercial dry plasma collection device (Chemcard Plasma Collection Device) and serum (venipuncture) from individuals in Kazakhstan. Plasma samples were air dried for 15 min and then stored desiccated in foil zip-lock pouches at 4 to 6 degrees C and subsequently shipped to the United States by air at ambient temperature. Serum samples remained frozen at -20 degrees C until assayed. Helicobacter pylori status was determined by enzyme-linked immunosorbent assay (HM-CAP EIA) for the dry plasma and the serum samples. The results were concordant in 250 of the 289 cases (86.5%). In 25 cases (8.6%), the dry plasma samples gave indeterminate results and could not be retested because only one sample was collected. Five serum samples were positive, and the corresponding dry plasma samples were negative; one serum sample was negative, and the corresponding plasma sample was positive. The relative sensitivity and specificity of the Chemcard samples to serum were 97.6 and 97.9%, respectively, excluding those with indeterminate results. Repeated freeze-thawing had no adverse effect on the accuracy of the test. We found the dry plasma collection device to provide an accurate and practical alternative to serum when venipuncture may be difficult or inconvenient and sample storage and handling present difficulties, especially for seroepidemiologic studies in rural areas or developing countries and where freeze-thawing may be unavoidable.

Blood Preservation↗
PubMed2006

Use of seroconversion panels to estimate delay in detection of anti-human immunodeficiency virus antibodies by enzyme-linked immunosorbent assay of pooled compared to singleton serum samples.

The transfusion of unsafe blood worldwide accounts for 5 to 15% of new human immunodeficiency virus (HIV) infections, most of which occur in sub-Saharan Africa. While developed countries now apply PCR testing of pooled samples, some developing countries still do not have universal screening policies. More efficient low-cost procedures for the screening of pooled samples have the potential to encourage mass screening efforts in resource-poor settings. The aim of this study was to estimate the delay in the detection of HIV antibodies in pooled serum samples compared to that in singleton serum samples by enzyme-linked immunosorbent assay (ELISA) and to evaluate the risk of transfusion-transmitted HIV infection during the window period. Serial blood samples obtained from five HIV seroconversion panels were mixed with HIV-seronegative blood samples to create pools of 6, 12, 16, 24, 32, and 48 samples. The delay in detection of the first anti-HIV antibody-positive sample in tests with pooled samples was calculated for each pool size and compared to that obtained by testing of singleton samples and statistically evaluated by a robust log-linear regression analysis. The risk of a false-negative (FN) result caused by dilution was estimated by use of the incidence risk/window period model. The additional risk of transmission related to ELISA screening of pooled samples for HIV did not exceed 9% of the current risk of an FN result (estimated to be 1/1,067,000). The countries with virus prevalence rates in donors of less than 15% are expected to save up to 30% in the number of tests. ELISA screening of pooled samples could be considered in settings where the testing of blood supplies for HIV is not routinely done.

Blood Donors↗
PubMed1998

Pooling urine samples for ligase chain reaction screening for genital Chlamydia trachomatis infection in asymptomatic women.

The accuracy of pooling urine samples for the detection of genital Chlamydia trachomatis infection by ligase chain reaction (LCR) was examined. A model was also developed to determine the number of samples to be pooled for optimal cost savings at various population prevalences. Estimated costs included technician time, laboratory consumables, and assay costs of testing pooled samples and retesting individual specimens from presumptive positive pools. Estimation of population prevalence based on the pooled LCR results was also applied. After individual urine specimens were processed, 568 specimens were pooled by 4 into 142 pools and another 520 specimens were pooled by 10 into 52 pools. For comparison, all 1,088 urine specimens were tested individually. The sample-to-cut-off ratio was lowered from 1.0 to 0.2 for pooled samples, after a pilot study which tested 148 samples pooled by 4 was conducted. The pooling algorithm was 100% (48 of 48) sensitive when samples were pooled by 4 and 98.4% (61 of 62) sensitive when samples were pooled by 10. Although 2.0% (2 of 99) of the negative pools of 4 and 7.1% (1 of 14) of the negative pools of 10 tested presumptive positive, all samples in these presumptive-positive pools were negative when retested individually, making the pooling algorithm 100% specific. In a population with 8% genital C. trachomatis prevalence, pooling by four would reduce costs by 39%. The model demonstrated that with a lower prevalence of 2%, pooling eight samples would reduce costs by 59%. Pooling urine samples for detection of C. trachomatis by LCR is sensitive, specific, and cost saving compared to testing individual samples.

Adolescent↗
PubMed2000

An important proportion of genital samples submitted for Chlamydia trachomatis detection by PCR contain small amounts of cellular DNA as measured by beta-globin gene amplification.

We assessed the quality of genital samples submitted for Chlamydia trachomatis detection by PCR by a second PCR assay for the presence of human beta-globin DNA. Endocervical and urethral samples were first tested by the COBAS AMPLICOR C. trachomatis assay (Roche Diagnostic Systems) with an internal control and were then amplified for the presence of beta-globin DNA with primers PC04 and GH20. Samples that contained inhibitors were retested after dilution 1:10. A total of 407 genital samples (311 endocervical swabs from 311 women and 96 urethral swabs from 95 men and 1 woman) collected over a 1-month period were evaluated. The internal control could not be amplified, despite dilution, from 3 of 23 samples that were retested after dilution because of inhibition, leaving 404 samples that could be analyzed by PCR. Eleven samples tested positive for C. trachomatis. Thirty (7.4%) of the 404 samples were negative for beta-globin. Twelve of the 23 undiluted samples that contained inhibitors tested positive for beta-globin DNA. Amplification of beta-globin DNA in samples submitted for C. trachomatis detection by the COBAS AMPLICOR C. trachomatis assay demonstrated that an important proportion of the samples did not contain cellular DNA. Assessment of the quality of the samples for PCR analysis by beta-globin amplification is feasible but cannot replace use of the internal control.

Cervix Uteri↗
PubMed2001

Comparison of cultivation and PCR-hybridization for detection of Salmonella in porcine fecal and water samples.

A total of 150 fecal and water samples from four swine farms were tested for the presence of Salmonella enterica using different enrichment techniques as follows: (i) 92 fecal samples from nursery and farrowing barns at three swine farms were preenriched overnight in tryptic soy broth (TSB) at 37 degrees C followed by overnight enrichment in Rappaport-Vassiliadis 10 broth (RV10) at 42 degrees C; (ii) 24 water samples from the third farm were preenriched overnight in 3MC broth at 37 degrees C followed by overnight enrichment in RV10 at 42 degrees C; and (iii) 34 fecal samples from a fourth farm, a finishing farm, were enriched overnight in RV10 at 42 degrees C with no additional enrichment. Following each of the enrichment techniques, samples were subcultured onto modified semisolid Rappaport-Vassiliadis (MSRV) agar prior to transfer to Hektoen Enteric agar plates for the recovery of viable Salmonella bacteria. Presumptive Salmonella isolates were biochemically and serologically confirmed. For the PCR detection of Salmonella, a 1-ml portion was removed from each sample after the first overnight enrichment and the DNA was extracted using a Sepharose CL-6B spin column. Amplicons (457 bp) derived from primers to the invA and invE genes were confirmed as Salmonella specific on ethidium bromide-stained agarose gels by Southern hybridization with a 20-mer oligonucleotide probe specific for the Salmonella invA gene. Neither the standard microbiological method nor the molecular method detected all of the 65 samples that tested positive by both methods or either method alone. Salmonella bacteria were detected by both cultivation and PCR-hybridization in 68% (17 of 25) of the positive samples that were preenriched in TSB, in 73% (11 of 15) of the positive samples preenriched in 3MC broth, and in 24% (6 of 25) of the positive samples enriched in RV10. Agreement between Salmonella detection using cultivation with preenrichment and detection by PCR was 76% using the kappa statistic. However, agreement between Salmonella detection using cultivation without preenrichment and detection by PCR was about 6%; the PCR assay detected 80% (20 of 25) of the 25 positive samples, while Salmonella bacteria were recovered from only 44% (11 of 25) by cultivation. Our results indicate that the PCR-hybridization approach is equivalent to or better than cultivation for detecting Salmonella in swine feces or water samples from swine farms when using the medium combinations evaluated in this study.

Animal Husbandry↗
PubMed1992

Survey of outpatient sputum cytology: influence of written instructions on sample quality and who benefits from investigation.

OBJECTIVES: To evaluated quality of outpatient sputum cytology and whether written instructions to patients improve sample quality and to identify variables that predict satisfactory samples. DESIGN: Prospective randomised study. SETTING: Outpatient department of a district general hospital. PATIENTS: 224 patients recruited over 18 months whenever their clinicians requested sputum cytology, randomized to receive oral or oral and written advice. INTERVENTIONS: Oral advice from nurse on producing a sputum sample (114 patients); oral advice plus written instructions (110). MAIN MEASURES: Percentages of satisfactory sputum samples and of patients who produced more than one satisfactory sample; clinical or radiological features identified from subsequent review of patients' notes and radiographs associated with satisfactory samples; final diagnosis of bronchial cancer. RESULTS: 588 sputum samples were requested and 477 received. Patients in the group receiving additional written instructions produced 75(34%) satisfactory samples and 43(39%) of them one or more sets of satisfactory samples. Corresponding figures for the group receiving only oral advice (80(31%) and 46(40%) respectively)were not significantly different. Logistic regression showed that radiological evidence of collapse or consolidation (p<0.01) and hilar mass (p<0.05) were significant predictors of the production of satisfactory samples. Sputum cytology confirmed the diagnosis in only 9(17%) patients with bronchial carcinoma. CONCLUSIONS: The quality of outpatients' sputum samples was poor and was not improved by written instructions. Sputum cytology should be limited to patients with probable bronchial cancer unsuitable for surgery. IMPLICATIONS: Collection of samples and requests for sputum cytology should be reviewed in other hospitals.

Bronchial Neoplasms↗
PubMed1991

Detection of Chlamydia trachomatis in urinary samples from women.

With a mean age of 21 years 197 women at risk for an infection with Chlamydia trachomatis (CT) had a urinary sample (20 ml first-void urine, minimum 4 hours from prior mictuation) analysed with an enzyme immunoassay (IDEIA-III) for the detection of CT. They also had samples taken from both cervix and urethra for cultivation on McCoy's cells and testing with an enzyme immunoassay (Chlamydiazyme), plus verification of positive samples in the enzyme immunoassay (EIA) with monoclonal antibodies against CT. The urethral samples were compared against the urinary samples with regard to sensitivity and specificity in detecting CT. Women with a positive culture for CT and/or a positive verified EIA from either the cervix or the urethra, were regarded as "true" infections with CT. The prevalence of CT was 12.2%. The urinary EIA sample had a sensitivity of 84% whereas the urethral EIA sample had a sensitivity of 57%. The specificity was 98% and 100% for the urinary samples, and the urethral samples respectively. It is concluded that the urinary sample is superior to the urethral sample, and that the urinary sample could be used for screening programs, to detect CT among women.

Adolescent↗
PubMed1986

Physiological properties of the luteinizing hormone pulse signal: impact of intensive and extended venous sampling paradigms on its characterization in healthy men and women.

The pulsatile nature of the gonadotropin signal is a critical determinant of physiological activation of the gonadal axis. Nonetheless, major uncertainties exist regarding the exact patterns of LH secretion that constitute normal physiological profiles in man. To assess possible bases for the discrepancies in the literature, we sampled blood at 5-min intervals for 24 h in eight normal men and eight normal women in the early follicular phase of the menstrual cycle. The constituent 5-, 10-, 15-, and 20-min immunoactive LH series and the consituent 6-, 12-, or 24-h sampling durations provided ranges of sampling intensities and durations for analysis of significant LH pulses. A technique for minimizing the influence of false positive immunoassay errors on peak detection was used to aid in estimating apparent true positive LH pulse frequency. Nonlinear curve fitting of the relationship between sampling intensity and apparent true positive LH pulse frequency revealed a stable pulse frequency estimate at intensive rates of venous sampling, with values of 19.5 +/- 1.9 (+/- SEM) pulses/24 h (periodicity, 73.8 +/- 6.5 min/pulse) in men and 20.6 +/- 3.6 pulses/24 h (periodicity, 70.0 +/- 10 min/pulse) in women. Further analyses indicated that sampling every 3.1 and 2.0 min for 24 h would be required to capture 90% of the LH pulses in men and women, respectively. Moreover, even with a 5-min sampling rate, the statistical counting errors of the LH pulse frequency estimates varied markedly with sampling duration; for example, in men sampled in 6-, 12-, and 24-hr sessions, the values were, respectively, 49%, 35%, and 24% of the observed pulse frequencies. Similar variations were found in women. Counting errors were 30-50% higher for conventional 20-min sampling rates than for 5-min sampling intervals. Measured interpulse intervals varied widely from 10-330 min (median, 60 min; n = 131 LH pulses) in men and from 10-340 min (median, 65 min; n = 125 LH pulses) in women. In addition, absolute LH pulse amplitudes varied from 1-28 mIU/ml (median, 4.1 mIU/ml) in men and from 1-24 mIU/ml (median, 3.6 mIU/ml) in women. These estimates were associated with a median number of points identified within each pulse of 6.0 in men and 4.0 in women. In summary, the present exhaustive sampling studies demonstrate for the first time stable estimates of physiological LH pulsations in normal men and women, and document broad ranges of normal LH pulse amplitudes and interpulse intervals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2005

Feasibility of using subject-collected dust samples in epidemiologic and clinical studies of indoor allergens.

Studies of indoor allergen exposures are often limited by the cost and logistics of sending technicians to homes to collect dust. In this study we evaluated the feasibility of having subjects collect their own dust samples. The objectives were to compare allergen concentrations between subject- and technician-collected samples and to examine the sample return rate. Using a dust collection device and written instructions provided to them by mail, 102 subjects collected a combined dust sample from a bed and bedroom floor. Later the same day, a technician collected a side-by-side sample. Dust samples were weighed and analyzed for the cat allergen Fel d 1 and the dust mite allergen Der p 1. Fifty additional subjects who were enrolled by telephone were mailed dust collection packages and asked to return a dust sample and questionnaire by mail. A technician did not visit their homes. Correlations between subject- and technician-collected samples were strong for concentrations of Fel d 1 (r = 0.88) and Der p 1 (r = 0.87). With allergen concentrations dichotomized at lower limits of detection and clinically relevant thresholds, agreements between methodologies ranged from 91 to 98%. Although dust weights were correlated (r = 0.48, p < 0.001), subjects collected lighter samples. Among the group of 50 subjects, 46 returned a dust sample and completed questionnaire. The median number of days to receive a sample was 15. With some limitations, subject-collected dust sampling appears to be a valid and practical option for epidemiologic and clinical studies that report allergen concentration as a measure of exposure.

Adult↗
PubMed2006

Natural history of alcohol dependence and remission events for a Native American sample.

OBJECTIVE: Examining the progression of a disorder cross- culturally may help distinguish elements common to addictions from those that are differentially shaped by culture. This study sought to construct a combined sequence of both problem emergence and recovery efforts with Native Americans. METHOD: In a cross-sectional sample, 44 adult Native Americans (61% men) who had resolved alcohol dependence completed face-to-face interviews at a research center. The Alcohol Related Behaviors Survey and the Change Effort Card-sorts along with measures of alcohol involvement and current quality of life were administered. RESULTS: This sample's sequence of alcohol-related events was compared to that reported for Jellinek's historical white male sample (r(s) = .46, p = .001), a recent Navajo sample (r(s) = .33, p = .024), and a recent Mission Indian sample (r(s) = .28, p = .24). This sample's sequence of change efforts was compared to that in the Navajo sample (r(s) = .33, p = .182). CONCLUSIONS: Despite the small sample size precluding generalizability, there was greater concordance between this intertribal sample and Jellinek's white male sample than between this sample and a Mission Indian sample, indicating both cross-cultural and intracultural variation. In addition, change efforts begin during the development of alcohol problems rather than waiting until the person "hits bottom," as suggested by previous research. Integrating the pathology of substance- use disorders with the process of resolving those disorders extends our understanding of the course of alcohol dependence.

Adult↗
PubMed1989

Use of an ambiguous-sample procedure to establish a cue to forget in pigeons.

Pigeons were trained on a variation of the matching-to-sample task in which on double-sample trials two samples, one associated with each of the comparison stimuli, were presented successively. Responding to the comparison associated with the first sample was reinforced on half the double-sample trials, and responding to the comparison associated with the second sample was reinforced on the remaining half. One of two postsample stimuli was presented following the termination of each colored sample. A vertical line was presented after a correct or target sample, and a horizontal line was presented after an incorrect or interfering sample. With extended training, each bird demonstrated above-chance accuracy on double-sample trials, providing prima facie evidence that one or both of the postsample stimuli exerted control over matching behavior. Experiment 2 provided evidence that the horizontal line functioned as a cue to forget the code activated by the preceding sample stimulus. It was concluded that a condition sufficient to establish a postsample stimulus as a cue to forget is that the postsample immediately follow presentation of a sample that, if it were to control test responding, would lead to nonreinforcement.

Journal Article↗
PubMed2003

Sampling correction in pedigree analysis.

Usually, a pedigree is sampled and included in the sample that is analyzed after following a predefined non-random sampling design comprising several specific procedures. To obtain a pedigree analysis result free from the bias caused by the sampling procedures, a correction is applied to the pedigree likelihood. The sampling procedures usually considered are: the pedigree ascertainment, determining whether a population unit is to be sampled; the intrafamilial pedigree extension, determining what part of the pedigree is to be sampled; and selective censoring of the sampled pedigree, determining whether it should be included in the sample to be analyzed. The probability of pedigree ascertainment is determined by the total set of potential probands in the true pedigree from which the sampled pedigree is obtained and we indicate how the necessary information on this set can be collected. If insufficient information on this set is observed, it is impossible to correct the pedigree likelihood adequately. Here we show that, if only the structure of this set is known, then an ascertainment-model-based pedigree likelihood can be obtained by conditioning on this structure. An ascertainment-model-free (AMF) pedigree likelihood can be correctly constructed by conditioning on all the data in this set, i.e. on both its structure and its phenotypic content. However, if this set has missing data, the AMF likelihood becomes undefined, which limits the utility of this AMF approach originally proposed by Ewens and Shute (1986). We also consider the sampling correction necessary when the pedigrees included in the sample analyzed have been subjected to censoring. The forms of likelihood correction developed here provide asymptotically unbiased estimators of the genetic model only if the formulated model is correct, which means that it must correctly allow for the most important features of the true inheritance of the trait studied. Otherwise, if no special case of the formulated general model is close to the true inheritance model, then the forms of likelihood correction proposed here result in biases, the magnitude and direction of which depend on both the true model and the general analysis model that should subsume it.

Journal Article↗