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Preoperative assessment of liver function.

At the present time, the decision to resect and the choice of the extent ofa hepatic resection are largely based on surgical judgment. The CP score is the best assessment tool we can now employ. There is uniform agreement that even segmental resections are not possible in the vast majority of Child Class B patients, CP score 7 to 9. The CP score can be augmented by radiographic testing, ICG retention testing, and by assessing tumor extent and the severity of the patient's cirrhosis at surgery. Surgeons need a simple means to assist with liver function evaluation--a test to augment the CP score. Although determining ICG retention is simple, it is questionable whether it adds to one's ability to define the poor-risk patient with better accuracy than the CP score. Abundant data exist to dispute the accuracy and reproducibility of ICG retention. That surgeons use it says more about the fervent desire to find a test that supports clinical judgment in these difficult patients than the scientific validity of the test. Whether a series of tests would better define the Child-Pugh Class A patient who is also a relatively poor risk is not clear at present. Many investigations demonstrate the correlation of various assessment tools with each other, yet nothing distinguishes them in predicting risk beyond what is learned from the CP score. In a group of CP Class A patients, the extent of the disease, the nature of underlying cirrhosis, and the extent of resection provide the clinical backdrop against which a decision for resection must be made. It may well be that one test may not do it, or that one single assessment of the ICG or the 15-minute receptor volume of GSA may be inadequate to project the nuances of liver function. Thus, 99m-Tc GSA scintigraphy will provide volumetric receptor data, as well as kinetic distribution curves, and may prove a useful test in the future. Whether GSA is ultimately to be proven useful requires a correlation of the test with actual clinical outcomes, rather than correlation with other tests or with the CP score. Discovering which patients are the poor risk Child Class A patients is the desired goal. To have value, the GSA scan must augment, not mimic, the CP score. In view of the fact that experienced surgeons appear to be astute in their ability to select patients for hepatic resection, finding a more refined test will require large numbers of patients at several centers to correlate the test results and the outcomes against the spectrum of postoperative liver failure, including death. It appears that one lesson learned from portal vein embolization is that functional liver volume can be preserved. The compensatory hyperplasia that occurs in the contralateral hepatic lobe demonstrates two important features: (1) function of the opposite lobe has been transferred when evaluated by 99m-Tc-GSA, and (2) one considerable metabolic drain on the postoperative recovery from hepatic resection (ie, liver regeneration) can be attended to before the surgery. Cirrhotic livers do regenerate, but more slowly. Thus, pregrowing the remnant section of liver eliminates one stress on liver reserves following liver resection. For hepatocellular carcinoma or metastasis in cirrhotic patients, portal vein occlusion may be the best way to improve hepatic functional reserve. ICG retention may not corroborate return-to-baseline hepatic function within 2 weeks of portal vein occlusion,but may demonstrate a return to baseline when studied 6 to 8 weeks following the procedure. 99m-Tc-GSA is presently the best means to document compensatory hyperplasia and, possibly, a shift of functional reserve to the planned remnant of a more than four-segment hepatic resection. Whether this will predict the safe outcome of resection remains to be seen.

Coloring Agents↗

Databases for congenital heart disease: A beginner's guide.

We discuss the reasons for collecting data on operations for congenital heart defects. Computerized databases facilitate the collection, storage, and retrieval of such data. We outline the basic criteria for selecting a suitable database to cater to the particular needs of a surgeon or a department and stress the importance of the accuracy of the data held in a database. We explain the relative advantage of simple versus complex database systems. We conclude with a summary of the steps required for a practicing congenital heart surgeon to set up and operate a simple database. Copyright 2000 by W.B. Saunders Company

Journal Article↗

Integrated function of a kinetic proofreading mechanism: dynamic analysis separating the effects of speed and substrate competition on accuracy.

All of the data relating to isoleucyl-tRNA synthetase and its proofreading of valyl-tRNAIle have been integrated into a single model whose dynamic behavior has been determined by numerical solution of the relevant kinetic equations. The results indicate that (1) the system normally operates in vivo with amino acid concentrations slightly above the apparent Km of the system, (2) increases in the displacement of reactants from thermodynamic equilibrium increase the net reaction velocity when the appropriate nominal parameter values are selected, (3) the cost of proofreading decreases with an increase in displacement of reactants from equilibrium, (4) accuracy and reaction velocity tend to be inversely related when substrate competition is unchanged but directly related or unrelated when substrate competition is altered, (5) changes in substrate competition are about twice as effective as changes in reaction velocity in altering the overall accuracy of aminoacylation, and (6) simultaneous changes in substrate competition and reaction velocity have a cumulative but not additive effect upon accuracy. With regard to the temporal development of errors and proofreading costs, we have seen two different patterns. In one, errors or costs gradually change with time following an abrupt alteration; in the other, errors or costs change dramatically in one direction and then more slowly reverse themselves. In all cases, the system responds to change quickly (less than 0.02-0.2 s) but shows no tendency to oscillate.

Amino Acyl-tRNA Synthetases↗

Multivariate data analysis of quality parameters in drinking water.

The quality of water destined for human consumption has been treated as a multivariate property. Since most of the quality parameters are obtained by applying analytical methods, the routine analytical laboratory (responsible for the accuracy of analytical data) has been treated as a process system for water quality estimation. Multivariate tools, based on principal component analysis (PCA) and partial least squares (PLS) regression, are used in the present paper to: (i) study the main factors of the latent data structure and (ii) characterize the water samples and the analytical methods in terms of multivariate quality control (MQC). Such tools could warn of both possible health risks related to anomalous sample composition and failures in the analytical methods.

Multivariate Analysis↗

A statistical method for flagging weak spots improves normalization and ratio estimates in microarrays.

Over the last few years, there has been a dramatic increase in the use of cDNA microarrays to monitor gene expression changes in biological systems. Data from these experiments are usually transformed into expression ratios between experimental samples and a common reference sample for subsequent data analysis. The accuracy of this critical transformation depends on two major parameters: the signal intensities and the normalization of the experiment vs. reference signal intensities. Here we describe and validate a new model for microarray signal intensity that has one multiplicative variation and one additive background variation. Using replicative experiments and simulated data, we found that the signal intensity is the most critical parameter that influences the performance of normalization, accuracy of ratio estimates, reproducibility, specificity, and sensitivity of microarray experiments. Therefore, we developed a statistical procedure to flag spots with weak signal intensity based on the standard deviation (delta(ij)) of background differences between a spot and the neighboring spots, i.e., a spot is considered as too weak if the signal is weaker than cdelta(ij). Our studies suggest that normalization and ratio estimates were unacceptable when this threshold (c) is small. We further showed that when a reasonable compromise of c (c = 6) is applied, normalization using trimmed mean of log ratios performed slightly better than global intensity and mean of ratios. These studies suggest that decreasing the background noise is critical to improve the quality of microarray experiments.

Animals↗

Simultaneous correction for interscan patient motion and geometric distortions in echoplanar imaging.

A method is presented for simultaneous correction of linear geometric distortions and interscan patient motion in echoplanar imaging (EPI). The technique does not require the acquisition of specialized scans other than high-resolution magnetic resonance images. The method is based on a generalized surface-based coregistration algorithm, which accounts for a complete 3-dimensional affine transformation, i.e., rotations, translations, scaling, and shearing, between two volumetric image data sets. Any minimally distorted high-resolution scan may serve as a reference data set, to which the EPI data set is matched. The algorithmic accuracy was assessed using simulated data sets with known affine distortions. The deviation of the parameters determined by the coregistration program from the true values typically was 1% or less. Precise alignment of functional and anatomic information will be important for many future clinical applications.

Algorithms↗

Malondialdehyde contents in infant milk formulas.

Malondialdehyde (MDA) levels in infant milk formulas have been monitored by using an aqueous acid extraction method combined with the thiobarbituric acid method (TBA-test). Vegetable oils, with a remarkable content of polyunsaturated fatty acids (PUFA) are used to enrich the infant milk formulas. As PUFA are more susceptible to autoxidation, it becomes of great interest to have information about the safety and preservation of these products. We monitored MDA content in twenty of the most popular infant milk formulas and in some commercial cow milk samples and compared the obtained data. Levels of MDA ranged between 200 and 1200 ppb: all values but one were higher, up to five times, than those found in cow milk samples. To evaluate the accuracy of the data obtained from the TBA-test, some samples were also analyzed with an HPLC derivative method: preliminary results show a good agreement between the two analytical techniques.

Animals↗

Comparison of European and American techniques for the analysis of volatile organic compounds in environmental matrices.

The United States Environmental Protection Agency has promulgated methods for analysis of volatile organic compounds by purge and trap, or dynamic headspace, gas chromatography. In western Europe, where environmental analyses are less heavily regulated, static headspace is widely used. In this paper, these two approaches are compared and contrasted for use with different environmental matrices. The theoretical basis and state of application for purge and trap and headspace analysis are discussed, and data are presented on the accuracy and precision of both approaches. Data are reported on the use of headspace analysis for different aqueous matrix types with different sample preparation procedures. A new method for direct headspace analysis of soil samples is presented and compared with the EPA-approved purge and trap method.

Chromatography, Gas↗

Hospice patient and caregiver congruence in reporting patients' symptom intensity.

As healthcare increasingly moves out of hospitals, the care of patients with cancer is provided in the community with the help of family caregivers. In many cases, nurses depend on family caregivers to provide assessment data about patients. This makes the accuracy and dependability of the data given by caregivers particularly important. However, it is not clear whether caregivers can accurately and dependably report such subjective data as symptom intensity. The purpose of this project was to evaluate the ability of the primary caregiver to report the symptom intensity of hospice patients with cancer. The sample consisted of 264 newly admitted adult patients with advanced cancer in hospice home care and their primary caregivers. These subjects were part of a large National Institutes of Health (NIH)-funded randomized clinical trial focused on symptom management and quality of life. The patients were alert and oriented. Among the questionnaires completed by both patients and caregivers on admission were numeric rating scales for pain and dyspnea and the Constipation Assessment Scale. All of these scales were designed to describe the patient's symptom intensity. The patient sample was predominantly white (83%) and male (57%), with a mean age of 71.6 years. The caregiver sample was predominantly white (85%) and female (78%), with a mean age of 62 years. The results indicated that caregivers significantly overestimated symptom intensity for all three symptoms (P =.000). Furthermore, the limited variance accounted for by the two sets of scores for each of the symptoms (R2 =.16-.26) indicated much more error in the scores than agreement between patient and caregiver. It appears that family caregivers cannot reliably report patient symptom intensity. Healthcare providers need to train family caregivers in conducting systematic assessments instead of assuming that they understand patient symptoms.

Aged↗

Image quality and diagnostic accuracy of 16-slice multidetector computed tomography for the detection of coronary artery disease in obese patients.

BACKGROUND: Cardiac multislice spiral computed tomography (MSCT) scanners permit visualization of the coronary arteries with an overall good sensitivity (sens) and specificity (spec). However, in obese patients (pts), who are at higher risk to develop coronary artery disease (CAD), image quality of MSCT is supposed to be limited. At present, there are no data whether the accuracy of MSCT depends on the body mass index (BMI). Thus, we compared the catheter-controlled MSCT results from normal weight and obese pts in a cohort of 117 pts with regard to sens, spec, positive predictive value (PPV), negative predictive value (NPV) and image quality. METHODS AND MATERIAL: In all, 21 normal weight pts (group I: BMI<25, 64.6+/-11.1 years, number of risk factors 2.1+/-1.1), 60 pts with mild overweight (group II: BMI 25-30, 64.6+/-8.9 years, number of risk factors 3.4+/-1.0) and 36 obese pts (group III: BMI >30, 63.0+/-8.5 years, number of risk factors 3.4+/-0.9) were examined by MSCT (Sensation 16 Speed 4 D((R)), Siemens, Germany, gantry rotation time 375 ms) and invasive coronary angiography. MSCT results were compared blinded to the results of the coronary angiography with regard to the presence or absence of a significant stenosis (>50%) in a modified AHA 13 segment (sgt) model. Image quality was assessed on a qualitative scale between 1 (very good) and 5 (insufficient image quality) for each sgt. RESULTS: Sens, spec, PPV and NPV were statistically not different in all three groups (I: 0.88/0.97/0.91/0.96, II: 0.83/0.97/0.88/0.95, III: 0.87/0.99/0.96/0.96). 3 pts (group I 1, group II 2) had to be excluded from analysis due to technical problems. Group I had significantly less risk factors (P < 0.001) and image quality was significantly better than in group II and III (P < 0.05). Group II and III did not differ with regard to risk factors or image quality. CONCLUSIONS: Overweight and obesity have an impact on MSCT image quality but did not hamper the diagnostic accuracy. Thus, MSCT is a noninvasive method to detect or rule out CAD also in pts with higher BMI. These retrospective data have to be confirmed in larger prospective trials.

Aged↗

Estimation of body fat in female rhesus monkeys.

Measurement of height (crown-rump length), body weight, and abdominal subcutaneous fat depth, based on skinfold thickness taken from 13 female rhesus monkeys comprising two age groups were correlated with body fat values derived from tritiated water determinations of total body water. The manner with which each measure was related to percent body fat differed as a function of age of the animal. In the young, nulliparous females, crown-rump length was the single best predictor of body fat, whereas in the older, multiparous females, skinfold thickness correlated most highly with body fat. When all measurements, including the Quetelet index [(wt/ht)2 x 1,000], were combined statistically and regressed against percent body fat, a significant increase in predictive ability was obtained. When each age group was considered separately, the resulting equations again reflected the age-group biases. In addition, as an internal check on the validity of the regression equations, an additional regression analysis was performed using morphometric data from selected animals in each age group. These equations yielded accurate estimates of body fat when compared to determinations made from total body water. These analyses indicate that the predictive accuracy of morphometric data is greatly enhanced by using these measurements in concert. Furthermore, the utility of such predictions is influenced by the specific physical characteristics of the subject population.

Adipose Tissue↗

Use of on-line gas analysis to monitor recombinant mammalian cell cultures.

The development of a system capable of accurately measuring the oxygen uptake and carbon dioxide production rates during mammalian cell cultures is described. A detailed study of the specifications of the various components used in the system for the measurement of gas flow rates and composition, coupled with the validation of the system independent of the bioreactor was carried out. The aim of this study was to identify and eliminate where possible the errors controlling the accuracy of determination of gaseous metabolic rates. This study showed the importance of controlling the temperature of gaseous oxygen entering the system. With such temperature control, it was possible to obtain data with an accuracy of +/- 5% at the 95% confidence level. Another source of error, the use of bi-carbonate buffer, was studied. A mathematical model was used to compensate for the affect of such buffers on the determination of carbon dioxide production rates. The use of the system for the continuous determination of gaseous metabolism during the growth and production phase for recombinant CHO cell cultures is described.

Animals↗

Mapping carbon monoxide using GPS tracked sensors.

In this paper we discuss a pilot study where we have mapped urban air pollution using mobile carbon monoxide (CO) sensors. Our objective is to use inexpensive Global Positioning System (GPS) receivers to track the sensors and explore CO variations at a fine geographic scale. The critical issue in data processing is the treatment of the imprecise logs from the GPS. By using knowledge about the route and the geometry of the buildings, we are able to increase the position accuracy significantly, while at the same time showing that certain events, such as CO profiles while crossing roads, can be detected with a high degree of accuracy. Comparisons between data from our own mobile sensors and a fixed sensor site show good agreement in the vicinity of the fixed sensor, while at the same time identifying significant CO peaks within 100 m of this location. Using the mobile sensors to collect data along two of the main roads in the area, we are able to show CO variations along an urban canyon for parallel and perpendicular wind directions. Finally, a number of significant sources of CO were discovered during the course of the study, which suggest possible locations for fixed sensor sites in the future. We conclude by discussing the results in the context of the push towards large sensor networks and mobile communications. The potential for ad hoc mobile sensor networks may be very large.

Air Pollutants↗

Height as a proxy for weight in determining azithromycin treatment for paediatric trachoma.

Azithromycin (Zithromax, Pfizer Inc., New York, NY, USA) is effective in the control of blinding trachoma. Community-based azithromycin treatment is recommended by the World Health Organization as part of a multipronged strategy aimed at the global elimination of binding trachoma by the year 2020. Paediatric trachoma is treated with azithromycin according to weight at a target dosage of 20 mg/kg. However, conventional weight-based treatment may be problematic in the field due to the logistical difficulties associated with weight scales. We assessed the accuracy of using height as a proxy for weight to determine azithromycin treatment in 4 countries--Viet Nam, Tanzania, Ghana, and Mali--where mass treatment programmes are underway. Population-based data collected from 1988 to 2000 were analysed using least squares regression. Height treatment schedules were developed for each data set. The accuracy of each schedule was evaluated according to the percentage of children receiving treatment within a dosage range of 20-30 mg/kg, a conservative estimate of the safe and effective treatment range for paediatric trachoma. Using height to determine dose, 89-95% of children would receive a dosage of 20-30 mg/kg. In these populations, height-based treatment is a reliable alternative to conventional weight-based treatment. Methods for developing height schedules presented in this analysis could be applied to other regions and therapeutics.

Administration, Oral↗

The reliability of digitized radiographs for dental identification: a Web-based study.

In the era of Daubert and other judicial rulings pertaining to the acceptability of forensic evidence, it is increasingly important that experts are able to testify that their methods have been scientifically tested and that error rates and other factors relating to reliability have been published. The purpose of this study was to determine the reliability of digitized radiographic comparisons for the purposes of dental identification. Participants with various forensic backgrounds and experience levels were passively recruited to the website. Ten forensic identification cases composed of antemortem and postmortem dental radiographs were supplied to examiners using a bespoke website. Participants responded to the cases on two occasions after a one-month washout interval using the ABFO conclusion levels for forensic identifications. A total of 115 first attempts and 87 matched second attempts were received. Of the total responses, 72% were dentally trained respondents who had completed at least one forensic identification case; of these, 38% were experienced forensic dentists who had completed more than 25 identifications. Data relating to accuracy, intra- and inter-examiner agreement, and the effect of case difficulty are presented. Mean accuracy was 85.5% for all cases, with the experienced forensic dentists obtaining a 91% success rate. The inter-examiner agreement on the negative identification cases was classified as poor. The data suggest that dental identifications resulting from the comparison of postmortem and antemortem radiographs are valid, accurate, and reliable when undertaken by experienced odontologists.

Analysis of Variance↗

Summary report of a national conference: Evolving concepts in liver allocation in the MELD and PELD era. December 8, 2003, Washington, DC, USA.

A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses. Conference participants used an evidence-based approach to consider whether predicted outcome after transplantation should influence allocation, to discuss the concept of minimal listing score, to revisit current and potential expansion of exception criteria, and to determine whether specific scores should be used for automatic removal of patients on the waiting list. After review of data from the first 18 months since implementation, association and society leaders, and surgeons and hepatologists with wide regional representation were invited to participate in small group discussions focusing on each of the main objectives. At the completion of the meeting, there was agreement that MELD has had a successful initial implementation, meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, and that it has proven to be a powerful tool for auditing the liver allocation system. It was also agreed that the data regarding the accuracy of PELD as a predictor of pretransplant mortality were less conclusive and that PELD should be considered in isolation. Recommendations for the transplant community, based on the analysis of the MELD data, were discussed and are presented in the summary document.

Adult↗

Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners.

BACKGROUND: It is uncertain whether male circumcision reduces the risks of penile human papillomavirus (HPV) infection in the man and of cervical cancer in his female partner. METHODS: We pooled data on 1913 couples enrolled in one of seven case-control studies of cervical carcinoma in situ and cervical cancer in five countries. Circumcision status was self-reported, and the accuracy of the data was confirmed by physical examination at three study sites. The presence or absence of penile HPV DNA was assessed by a polymerase-chain-reaction assay in 1520 men and yielded a valid result in the case of 1139 men (74.9 percent). RESULTS: Penile HPV was detected in 166 of the 847 uncircumcised men (19.6 percent) and in 16 of the 292 circumcised men (5.5 percent). After adjustment for age at first intercourse, lifetime number of sexual partners, and other potential confounders, circumcised men were less likely than uncircumcised men to have HPV infection (odds ratio, 0.37; 95 percent confidence interval, 0.16 to 0.85). Monogamous women whose male partners had six or more sexual partners and were circumcised had a lower risk of cervical cancer than women whose partners were uncircumcised (adjusted odds ratio, 0.42; 95 percent confidence interval, 0.23 to 0.79). Results were similar in the subgroup of men in whom circumcision was confirmed by medical examination. CONCLUSIONS: Male circumcision is associated with a reduced risk of penile HPV infection and, in the case of men with a history of multiple sexual partners, a reduced risk of cervical cancer in their current female partners.

Adult↗

Accuracy and reproducibility of a subpixel extended phase correlation method to determine micron level displacements in the heart.

Future treatment of heart disease may involve local perturbations of mechanical function, such as intramyocardial injections of angiogenic growth factors or progenitor cells. This necessitates an accurate measurement technique to determine regional heart function. We have previously developed a method to determine regional heart function using a phase correlation algorithm. However, in determining regional function over a single heartbeat it is necessary to sum displacements between many images. We have therefore incorporated a subpixel algorithm that models the result of phase correlation as a sinc function in order to increase the accuracy of our technique. This method, which we have named high density mapping (HDM), determines the subpixel displacement of 64 x 64 pixel regions from images of the heart. To determine the accuracy and precision of the technique, a high contrast image of a heart was digitally shifted 1, 2 or 3 pixels. The original and shifted images were then downsampled four times resulting in 0.25, 0.50 or 0.75 pixel shifts between the original and shifted images. The average accuracy of HDM in the digitally shifted images was 0.06 pixels, with a precision of 0.08 pixels. Effectiveness of HDM in characterization of deformation was also assessed in digitally stretched images. Error in quantification of strain was found to be less than 3.5% of the calculated strain. In an additional set of experiments, in which accuracy was determined using physical motion instead of digital shifting and downsampling, a speckle pattern was displaced by known distances using a micromanipulator, such that the displacement between the captured images was 0.5 pixels. These data demonstrated an accuracy of 0.09 pixels and a precision of 0.02 pixels. Finally, as HDM is used to determine the regional stroke work index (RSW) in beating hearts, the repeatability of using this method to compute RSW was assessed. RSW, the integral of intraventricular pressure with respect to unitless regional area, where end diastolic area was normalized to unity, was assessed in consecutive beats from four different hearts. The average standard deviation of RSW was 0.098 mmHg. Uncertainty analysis determined the maximum error of RSW to be +/-0.41 mmHg, approximately two-thirds of the measured biologic variability. These data demonstrate the ability of HDM to accurately and reproducibly measure displacement and regional function in the beating heart.

Algorithms↗