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PubMed1969

Quantum efficiency and false positive rate.

1. This paper presents an analysis of the efficiency of performance at the absolute threshold of human vision. The data are from the same series as the previous papers (Hallett, 1969b, c) and consist of frequency-of-seeing curves, thresholds, false positive rates and equivalent background measurements, accumulated as small samples over a number of days.2. Quantum efficiency is defined here as the ratio of the thresholds of an ideal and a real detector performing the same task with the same sampling error. This avoids the problem as to whether the frequency-of-seeing curve of the real detector is exactly a Poisson sum or not.3. The long-term quantum efficiency can be low (about 0.04) as a result of drifts in the mean threshold.4. The average short-term quantum efficiency is in the region of 0.1, which is roughly the physiological limit set by Rushton's (1956b) measurements of rhodopsin density in the living rods. If this is correct, then the absorption of a quantum, and not the bleaching of a rhodopsin molecule, is sufficient for the generation of a neural event.5. Application of a simple signal/noise theory to the data gives solutions close to those suggested by Barlow (1956) and shows that false positives almost invariably arise from errors subsequent to the signal/noise decision process.

Dark Adaptation↗

PubMed2005

On the comparison of FROC curves in mammography CAD systems.

We present a novel method for assessing the performance of computer-aided detection systems on unseen cases at a given sensitivity level. The sampling error introduced when training the system on a limited data set is captured as the uncertainty in determining the system threshold that would yield a certain predetermined sensitivity on unseen data sets. By estimating the distribution of system thresholds, we construct a confidence interval for the expected number of false positive markings per image at a given sensitivity. We present two alternative procedures for estimating the probability density functions needed for the construction of the confidence interval. The first is based on the common assumption of Poisson distributed number of false positive markings per image. This procedure also relies on the assumption of independence between false positives and sensitivity, an assumption that can be relaxed with the second procedure, which is nonparametric. The second procedure uses the bootstrap applied to the data generated in the leave-one-out construction of the FROC curve, and is a fast and robust way of obtaining the desired confidence interval. Standard FROC curve analysis does not account for the uncertainty in setting the system threshold, so this method should allow for a more fair comparison of different systems. The resulting confidence intervals are surprisingly wide. For our system a conventional FROC curve analysis yields 0.47 false positive markings per image at 90% sensitivity. The 90% confidence interval for the number of false positive markings per image is (0.28, 1.02) with the parametric procedure and (0.27, 1.04) with the nonparametric bootstrap. Due to its computational simplicity and its allowing more fair comparisons between systems, we propose this method as a complement to the traditionally presented FROC curves.

Algorithms↗

PubMedDate not supplied

Fluorescence bronchoscopy for localization of carcinoma in situ.

A fluorescence bronchoscope system has been developed for imaging lung tumors by fluorescence of a previously injected, tumor-specific agent hematoporphyrin derivative. Carcinoma in situ has been localized, but there are too many false positives and negatives. A new system has been implemented which allows rapid switching between viewing of fluorescence, and viewing of the same area under white light illumination as in conventional bronchoscopy. The excitation source is a violet krypton ion laser coupled to a fused quartz fiber light conductor, with a diverging microlens to spread the light uniformly. A third-generation, microchannel plate image intensifier amplifies the weak fluorescence for viewing and video display, recording, and analysis. A movable mirror and periscope bypasses the intensifier for normal color viewing and video display and recording, with the laser shutter closed and the white light shutter open. This facilitates accurate localization, comparison of the color and fluorescence images, and precise sampling during biopsy. The improved system should reduce the false positive rate due to biopsy sampling error, and together with the video analyzer should reduce indeterminate results.

Bronchoscopes↗

PubMed1968

Microbiology of anaerobic sludge fermentation. I. Enumeration of the nonmethanogenic anaerobic bacteria.

An anaerobic medium containing sludge supernatant fluid and glucose was used for enumeration of bacteria from the sludge fermentation. Comparison of viable counts from several separate samples consistently showed 10 to 100 times more anaerobic than aerobic bacteria. However, viable counts of the various samples differed by as much as 10 times; this variation probably reflects a change in the natural environment or sampling errors, or a combination of the two. Direct microscopic counts yielded values of about 10(10)/ml. The discrepancy between viable (10(8) to 10(9)/ml) and direct counts may be due to large numbers of dead cells. Random isolates of representative colonies from high dilutions exhibited the ability to ferment sugars and are not likely to be methane bacteria.

Bacteria↗

PubMed2003

Measurement of inflammatory biomarkers in synovial tissue extracts by enzyme-linked immunosorbent assay.

We developed methods for measuring inflammatory biomarkers (cytokines, chemokines, and metalloproteinases) in synovial biopsy specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Soluble extracts of synovial fragments were prepared with mild detergent and analyzed by enzyme-linked immunosorbent assay (ELISA) for interleukin 1beta (IL-1beta), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and matrix metalloproteinase 3. The optimal detergent was 0.1% Igepal CA-630, which interfered minimally with ELISA detection but extracted 80% of IL-6 from synovial tissue. Upon spiking, 81 to 107% of added biomarkers could be recovered. To determine within-tissue variability, multiple biopsy specimens from each RA synovial extract were analyzed individually. A resulting coefficient of variation of 35 to 62% indicated that six biopsy specimens per synovial extract would result in a sampling error of < or = 25%. Preliminary power analysis suggested that 8 to 15 patients per group would suffice to observe a threefold difference before and after treatment in a serial biopsy clinical study. The previously described significant differences in IL-1beta, IL-6, IL-8, and TNF-alpha levels between RA and OA could be detected, thereby validating the use of synovial extracts for biomarker analysis in arthritis. These methods allow monitoring of biomarker protein levels in synovial tissue and could potentially be applied to early-phase clinical trials to provide a preliminary estimate of drug efficacy.

Arthritis, Rheumatoid↗

PubMed1987

Variability of the turgor pressure of individual cells of the gram-negative heterotroph Ancylobacter aquaticus.

Cells of Ancylobacter aquaticus were observed under phase microscopy in a chamber to which a measured pressure could be applied. The initial collapse pressure (Ca), i.e., the lowest pressure needed to collapse the most pressure-sensitive gas vesicles, was measured for 69 cells. The cells were taken from cultures in low-density balanced exponential growth, and the experiments were performed quickly so that the bacteria were in a uniform physiological state at the time of measurement. The turgor pressure, Pt, is the difference between the pressure, C, that would cause collapse of vesicles when removed from the cell and Ca. In this paper we focus on the variability of Pt from cell to cell. Part of the observed variability of Ca was due to the variability of the collapse pressure of individual vesicles (standard deviation [SD] = 90 kPa), but because there were about 100 vesicles per cell and because a change in refracted light after the fifth vesicle (approximately) collapsed probably could be detected by the human eye, the pressure would only have an SD of 18.6 kPa due to this type of sampling error. The observed SD of Pt was 42 kPa, indicating that turgor pressure did vary considerably from cell to cell. However, the turgor pressure was independent of cell size. Statistical analysis showed that Pt would decrease 6.9 kPa over a cell cycle, but with too large an SD (19.9 kPa) to be significant. This implies that the observed change in Pt over the cell cycle is not statistically significant.

Cell Cycle↗

PubMed1990

Evaluation of three Chlamydia trachomatis immunoassays with an unbiased, noninvasive clinical sample.

First-catch early morning urine samples from patients attending a genitourinary medicine clinic were tested by three different enzyme immunoassays. The results suggest significant differences in the sensitivities and specificities of the different assays. The direct visualization of elementary bodies in urine deposits by direct immunofluorescence was used as the "gold standard," using a monoclonal antibody with a different epitope specificity from those of antibodies used in the enzyme-linked immunosorbent assays. We report for the first time that urine specimens represent an unbiased sample, free of the inherent sampling errors associated with other genital specimens. We feel that urine is a valid specimen for use in any evaluation study of new assays directed towards the detection of Chlamydia trachomatis.

Antigens, Bacterial↗

PubMed1997

Immunoblot assay for serodiagnosis of Helicobacter pylori infections.

An immunoblot assay for the serological diagnosis of Helicobacter pylori infection was evaluated. Serum samples from patients whose gastric biopsy specimens were known to be positive or negative for H. pylori on culture were used to establish interpretive criteria for the immunoblot assay. A panel of sera from patients with diseases other than H. pylori infection and sera from healthy blood donors were included to validate these criteria. All sera were initially assessed in an enzyme immunoassay (Ge-EIA), based on acid glycine-extracted cell surface proteins of H. pylori NCTC 11637. The same antigen extract was used in the immunoblot assay. In addition, the Ge-EIA and the immunoblot assay were compared with a commercially available EIA (Seradyn, Color Vue Pylori). Bands of 110/120 kDa and/or two of five low-molecular-mass proteins (26, 29, 30, 31, and 33 kDa, in any combination) showed a strong correlation with the H. pylori culture-positive patients (97.5%) compared to the correlation obtained with the EIA results (Ge-EIA, 87.5%; Seradyn EIA, 92.5%), and the antibody responses to these proteins were considered specific reactions. In 37 of 40 serum samples from culture-negative patients and also in sera from patients with other disorders, a moderate antibody reactivity to the medium-size proteins (43 to 66 kDa) was observed, and these were considered not valuable for a specific immunoblot assay. Among sera from culture-positive patients, 39 of 40 serum samples were defined to be immunoblot positive, and from among sera from culture-negative patients, 3 of 40 serum samples were defined to be immunoblot positive. The use of sera from patients with negative cultures for H. pylori as negative controls may decrease the sensitivity due to sampling error and false-negative culture results. Immunoblot assay-positive results were detected among 10% of sera from patients with other diseases, whereas they were detected among 42.5% of sera by the Ge-EIA and 47.5% of sera by the Seradyn-EIA. The higher number of EIA-positive sera in this group reflects a possible cross-reactivity (false-positive EIA result). Of the blood donors, representing asymptomatic but possibly colonized subjects, 24% were immunoblot positive. In conclusion, our data indicate that immunoblotting is more sensitive as well as more specific than EIA. Moreover, it permits detection of antibody responses to specific antigens, e.g., the cytotoxin-associated CagA protein, which may have pathological implications.

Adult↗

PubMed1999

Identification of biased amino acid substitution patterns in human immunodeficiency virus type 1 isolates from patients treated with protease inhibitors.

Human immunodeficiency virus type 1 (HIV-1) amino acid substitutions observed during antiretroviral drug therapy may be caused by drug selection, non-drug-related evolution, or sampling error introduced by the sequencing process. We analyzed HIV-1 sequences from 371 untreated patients and from 178 patients receiving a single protease inhibitor. Amino acid substitution patterns during treatment were compared with inferred substitution patterns arising evolutionarily without treatment. Our results suggest that most treatment-associated amino acid substitutions are caused by selective drug pressure, including substitutions not previously associated with drug resistance.

Amino Acid Sequence↗

PubMed1995

Using data from the 1991 census.

The 1991 census for England and Wales provides a substantial amount of data on demography, ethnicity, housing tenure, employment status, and other social factors for geographical areas ranging in size from enumeration districts upwards. Many in the health service and in the academic community are making use of the data in the 1991 census. However, users of census data need to be aware of the problems and limitations of these data, which include the format of the data, data modification and suppression, sampling error, and underenumeration. An important innovation of the 1991 census was that the census form included a question on the postcode of respondents; this allowed the Office of Population Censuses and Surveys to produce a postcode-enumeration district look up table which overcomes many of the problems previously encountered in trying to assign postcodes to enumeration districts. The new look up table also includes the grid reference of postcodes, and this will improve the geographical referencing of census data.

Data Collection↗

PubMed1979

Value of sigmoidoscopy and biopsy in detection of carcinoma and premalignant change in ulcerative colitis.

Of 111 carcinomas developing in 73 patients with ulcerative colitis, 46 (41.5%) arose in the rectum where they are directly accessible to sigmoidoscopy. Fifty-eight per cent of single carcinomas developed in the rectum. The extent and frequency of rectal dysplasia was assessed by examining slides of rectal mucosa with an eyepiece micrometer. Slides from 46 patients with carcinoma and 22 patients with dysplasia but no carcinoma in whom proctectomy or proctocolectomy had been carried out were examined by this method. Thirteen of 15 patients with carcinoma of the colon (87%) and 21/22 patients (95%) with large bowel dysplasia showed evidence only of rectal dysplasia. However, there was marked variability in the proportion of dysplastic rectal mucosa even in those patients with rectal carcinoma, while in some patients dysplasia was limited to a small focus. Because of the possibility of false negative biopsies due to sampling error, multiple biopsies should be taken to detect dysplasia. Their state should be recorded and deliberately varied at subsequent visits. Careful sigmoidoscopy and multiple biopsies in this study had potential value as an aid in the detection of 85-90% of all carcinomas. In practice the figure would almost certainly be lower due to intrinsic bias (see discussion) so that, although regular sigmoidoscopy and biopsy would be of great value when colonoscopy is not available, the latter should be included in any long-term programme of carcinoma prevention.

Biopsy↗

PubMed1990

Ultrasonically guided histological and cytological fine needle biopsies of the pancreas. Reliability and reproducibility of diagnoses.

In 100 consecutive patients ultrasonically guided histological and cytological fine needle biopsy specimens were obtained from pancreatic lesions using two different needles with an outer diameter of 0.6 mm. Specimens taken by both cytological and histological fine needle biopsy were examined blindly by two pathologists. When related to the final and reliable diagnosis obtained in 57 patients, the predictive value of a malignant diagnosis was 1.00 for both types of biopsy. The predictive value for a benign diagnosis was 0.25 for histological specimens for both examiners and 0.33 and 0.45 for the two evaluations of the cytological specimens. False benign diagnoses seemed to be related to both sampling error and difficulties in interpreting the biopsy specimens. The intraobserver and interobserver kappa values concerning reproducibility of diagnoses were higher for histological specimens (0.80 and 0.74) than for cytological specimens (0.70 and 0.61). Consistent malignant diagnoses, however, occurred more often with cytological specimens (51 cases) than with histological specimens (39 cases) (p less than 0.05) and consistent diagnoses of insufficient material were more common with histological specimens (18 cases v six cases). Cytological fine needle biopsy seems to be the method of choice if only one method is used and a 0.6 mm needle is used.

Adult↗

PubMed1994

Role of right ventricular endomyocardial biopsy in infants and children with suspected or possible myocarditis.

OBJECTIVES: To assess the diagnostic yield, sampling errors, risks, and therapeutic implications of right ventricular endomyocardial biopsy in children with suspected or possible myocarditis. DESIGN: Retrospective study. SETTING: Tertiary referral centre for paediatric cardiology, cardiac surgery, heart transplantation, and mechanical circulatory support. PATIENTS AND METHODS: Review of clinical and histological findings among 63 consecutive children with possible myocarditis undergoing right ventricular endomyocardial biopsy. Review of cardiac histology at subsequent necropsy or after explantation at time of transplantation. RESULTS: From January 1980 to December 1992, 76 biopsies were performed in 63 children (2 weeks to 18 years of age). In 41 cases, the biopsy was performed for evaluation of dilated cardiomyopathy. The median interval from onset of symptoms was one month. Eight children (20%; all with a history of less than six weeks duration) had biopsy proved myocarditis. Five of the eight children made a full recovery, including four who presented in cardiogenic shock. By contrast, only three of 33 children without evidence of myocarditis showed recovery of ventricular function. The whole heart was available for histological examination in 23 patients. Myocarditis was confirmed in one patient, and no evidence of myocarditis was found in the remaining 22 (all with negative biopsies). One procedure related death occurred in a 2 week old infant with dilated cardiomyopathy. In 22 cases, biopsy was performed for the evaluation of arrhythmia. Only one biopsy showed myocarditis. CONCLUSIONS: The diagnostic yield of a biopsy is low in children with arrhythmias. In children presenting with profound ventricular dysfunction, a diagnosis of acute myocarditis may avoid premature consideration of transplantation as this group has an important potential for full recovery. In less critically ill patients and in those with a longer duration of symptoms the justification for biopsy is not as clear and the procedure is not without risk.

Acute Disease↗

PubMed2006

Accuracy of frozen section in the diagnosis of liver mass lesions.

OBJECTIVE: To evaluate the diagnostic accuracy of intraoperative frozen sections diagnosis of liver lesions thought to be malignant tumours. METHODS: 285 frozen sections of liver from 173 patients were reviewed. The examinations were done between 1998 and 2004. RESULTS: Final histological diagnosis was divided into positive (32%) and negative (68%) for malignancy. In four cases (2%), diagnosis was deferred to paraffin section. There was one false positive and two false negative diagnoses. Sensitivity was 96.9% and specificity was 99.1%, and the overall accuracy to determine the lesions was 95%. The cases were further analysed to ascertain the nature of diagnostic difficulties, which comprised pathological misinterpretation, sampling error, and technical imperfections. Biliary hamartoma was the most common entity that was confused with malignant tumours in frozen sections. CONCLUSIONS: The data are in accordance with those of similar studies in other sites, and confirm that the frozen section is an accurate and reliable method for intraoperative diagnosis of suspected liver lesions.

Adolescent↗

PubMed1970

Adsorption of serum calcium by plastic sample cups.

Sera left overnight in plastic AutoAnalyzer sample cups may give low calcium values; the effect is attributed to adsorption of calcium onto the walls of the vessel. The adsorption is brought about by a rise in the pH of the sera, and factors which promote the rise in pH increase the adsorption. This phenomenon is of practical importance because as much as 10% of the calcium in the serum may be adsorbed. Adsorption occurs particularly onto the walls of polystyrene cups, and when polypropylene cups were used the adsorption was reduced. The phenomenon cannot be evaluated or controlled by the use of control sera. In order to avoid the sampling error, serum for calcium analysis should be used fresh or stored at 4 degrees C under conditions such that any change in pH is minimal. Sera should not be left to stand in AutoAnalyzer cups at room temperature for longer than three hours before analysis.

Adsorption↗

PubMed1974

Differential white cell counts by frequency distribution analysis of cell volumes.

Absolute neutrophil and lymphocyte counts on peripheral blood can be made by analysis of the output from a Coulter particle counter, utilizing the difference in the relative cell volume between these two types of cell. A comparison has been made between the results obtained by volume analysis and those obtained by standard microscopical techniques in 10 normal people and 45 patients. The absolute neutrophil count obtained by volume analysis agreed well with values obtained by microscopy; the lymphocyte count did not give such good agreement, since the smaller number of cells counted gave rise to larger sampling errors. The method of volume analysis is suitable for the assessment of absolute neutrophil counts for clinical use.

Blood Cell Count↗

PubMed1975

Orcein staining of hepatitis B antigen in paraffin sections of liver biopsies.

Liver biopsies from 97 hepatitis B antigen (HBsAG)-positive patients were stained by a modified orcein method described by Shikata et al (1974) in order to detect the antigen in liver tissue. The results were consitently negative in acute hepatitis, but positive in nearly two-thirds of biopsies from 53 patients with chronic liver disease. The distribution of positive staining was frequently irregular so that there is a problem of sampling error in needle biopsies. The deposits were seen in the cytoplasm of liver cells and occasionally in Kupffer cells, but never in nuclei. There was an inverse relationship between staining and parenchymal necrosis. Biopsies from asymptomatic HB(s)Ag carriers were often strongly positive, as were "ground-glass" hepatocytes in carriers and patients with chronic liver disease. The mechanism of staining is unclear but may be related to the presence of disulphide bonds in (HBsAG. The technique is simple and of use both in fresh and stored material.

Acute Disease↗

PubMed1982

Medical audit of rectal biopsy diagnosis of inflammatory bowel disease.

The records of the rectal biopsy diagnoses of ulcerative colitis and Crohn's disease in the Department of Pathology, St Mark's Hospital, London, were reviewed. The biopsy diagnoses were compared to subsequent resection diagnoses on the same patients, and annual and seasonal variations in the frequency of these and related diagnoses were studied. The accuracy rate for the biopsy diagnosis of ulcerative colitis was about 70% and for Crohn's disease about 40% each time a biopsy was read. The low figure for the accuracy rate for Crohn's disease could be attributed to sampling error inherent in the diagnosis of a disease which is essentially patchy, showing discontinuous pathology. Also, many patients with Crohn's disease have a normal rectum which is biopsied to demonstrate the distinction from ulcerative colitis. In practical terms therefore a 40% accuracy rate in Crohn's disease is probably adequate. The rate of "false-positive" diagnoses was about 5%. There was a seasonal variation in the frequency of these two diagnoses, but no variation attributable to changes in observers, as pathology trainees in the Department change regularly. The frequency of diagnoses of non-specific inflammation and of normal colon did show such non-random variations.

Adenocarcinoma↗