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Results for “Software Validation”

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At least 289 records · Page 16Linked to original sources

PubMed2000

Risk-adjusting acute myocardial infarction mortality: are APR-DRGs the right tool?

OBJECTIVE: To determine if a widely used proprietary risk-adjustment system, APR-DRGs, misadjusts for severity of illness and misclassifies provider performance. DATA SOURCES: (1) Discharge abstracts for 116,174 noninstitutionalized adults with acute myocardial infarction (AMI) admitted to nonfederal California hospitals in 1991-1993; (2) inpatient medical records for a stratified probability sample of 974 patients with AMIs admitted to 30 California hospitals between July 31, 1990 and May 31, 1991. STUDY DESIGN: Using the 1991-1993 data set, we evaluated the predictive performance of APR-DRGs Version 12. Using the 1990/1991 validation sample, we assessed the effect of assigning APR-DRGs based on different sources of ICD-9-CM data. DATA COLLECTION/EXTRACTION METHODS: Trained, blinded coders reabstracted all ICD-9-CM diagnoses and procedures, and established the timing of each diagnosis. APR-DRG Risk of Mortality and Severity of Illness classes were assigned based on (1) all hospital-reported diagnoses, (2) all reabstracted diagnoses, and (3) reabstracted diagnoses present at admission. The outcome variables were 30-day mortality in the 1991-1993 data set and 30-day inpatient mortality in the 1990/1991 validation sample. PRINCIPAL FINDINGS: The APR-DRG Risk of Mortality class was a strong predictor of death (c = .831-.847), but was further enhanced by adding age and sex. Reabstracting diagnoses improved the apparent performance of APR-DRGs (c = .93 versus c = .87), while using only the diagnoses present at admission decreased apparent performance (c = .74). Reabstracting diagnoses had less effect on hospitals' expected mortality rates (r = .83-.85) than using diagnoses present at admission instead of all reabstracted diagnoses (r = .72-.77). There was fair agreement in classifying hospital performance based on these three sets of diagnostic data (K = 0.35-0.38). CONCLUSIONS: The APR-DRG Risk of Mortality system is a powerful risk-adjustment tool, largely because it includes all relevant diagnoses, regardless of timing. Although some late diagnoses may not be preventable, APR-DRGs appear suitable only if one assumes that none is preventable.

Adult↗

PubMedDate not supplied

Benchmarking of linear and nonlinear approaches for quantitative structure-property relationship studies of metal complexation with ionophores.

A benchmark of several popular methods, Associative Neural Networks (ANN), Support Vector Machines (SVM), k Nearest Neighbors (kNN), Maximal Margin Linear Programming (MMLP), Radial Basis Function Neural Network (RBFNN), and Multiple Linear Regression (MLR), is reported for quantitative-structure property relationships (QSPR) of stability constants logK1 for the 1:1 (M:L) and logbeta2 for 1:2 complexes of metal cations Ag+ and Eu3+ with diverse sets of organic molecules in water at 298 K and ionic strength 0.1 M. The methods were tested on three types of descriptors: molecular descriptors including E-state values, counts of atoms determined for E-state atom types, and substructural molecular fragments (SMF). Comparison of the models was performed using a 5-fold external cross-validation procedure. Robust statistical tests (bootstrap and Kolmogorov-Smirnov statistics) were employed to evaluate the significance of calculated models. The Wilcoxon signed-rank test was used to compare the performance of methods. Individual structure-complexation property models obtained with nonlinear methods demonstrated a significantly better performance than the models built using multilinear regression analysis (MLRA). However, the averaging of several MLRA models based on SMF descriptors provided as good of a prediction as the most efficient nonlinear techniques. Support Vector Machines and Associative Neural Networks contributed in the largest number of significant models. Models based on fragments (SMF descriptors and E-state counts) had higher prediction ability than those based on E-state indices. The use of SMF descriptors and E-state counts provided similar results, whereas E-state indices lead to less significant models. The current study illustrates the difficulties of quantitative comparison of different methods: conclusions based only on one data set without appropriate statistical tests could be wrong.

Algorithms↗

PubMed2005

Validation of the Monte Carlo simulator GATE for indium-111 imaging.

Monte Carlo simulations are useful for optimizing and assessing single photon emission computed tomography (SPECT) protocols, especially when aiming at measuring quantitative parameters from SPECT images. Before Monte Carlo simulated data can be trusted, the simulation model must be validated. The purpose of this work was to validate the use of GATE, a new Monte Carlo simulation platform based on GEANT4, for modelling indium-111 SPECT data, the quantification of which is of foremost importance for dosimetric studies. To that end, acquisitions of (111)In line sources in air and in water and of a cylindrical phantom were performed, together with the corresponding simulations. The simulation model included Monte Carlo modelling of the camera collimator and of a back-compartment accounting for photomultiplier tubes and associated electronics. Energy spectra, spatial resolution, sensitivity values, images and count profiles obtained for experimental and simulated data were compared. An excellent agreement was found between experimental and simulated energy spectra. For source-to-collimator distances varying from 0 to 20 cm, simulated and experimental spatial resolution differed by less than 2% in air, while the simulated sensitivity values were within 4% of the experimental values. The simulation of the cylindrical phantom closely reproduced the experimental data. These results suggest that GATE enables accurate simulation of (111)In SPECT acquisitions.

Algorithms↗

PubMed2003

EST mining and functional expression assays identify extracellular effector proteins from the plant pathogen Phytophthora.

Plant pathogenic microbes have the remarkable ability to manipulate biochemical, physiological, and morphological processes in their host plants. These manipulations are achieved through a diverse array of effector molecules that can either promote infection or trigger defense responses. We describe a general functional genomics approach aimed at identifying extracellular effector proteins from plant pathogenic microorganisms by combining data mining of expressed sequence tags (ESTs) with virus-based high-throughput functional expression assays in plants. PexFinder, an algorithm for automated identification of extracellular proteins from EST data sets, was developed and applied to 2147 ESTs from the oomycete plant pathogen Phytophthora infestans. The program identified 261 ESTs (12.2%) corresponding to a set of 142 nonredundant Pex (Phytophthora extracellular protein) cDNAs. Of these, 78 (55%) Pex cDNAs were novel with no significant matches in public databases. Validation of PexFinder was performed using proteomic analysis of secreted protein of P. infestans. To identify which of the Pex cDNAs encode effector proteins that manipulate plant processes, high-throughput functional expression assays in plants were performed on 63 of the identified cDNAs using an Agrobacterium tumefaciens binary vector carrying the potato virus X (PVX) genome. This led to the discovery of two novel necrosis-inducing cDNAs, crn1 and crn2, encoding extracellular proteins that belong to a large and complex protein family in Phytophthora. Further characterization of the crn genes indicated that they are both expressed in P. infestans during colonization of the host plant tomato and that crn2 induced defense-response genes in tomato. Our results indicate that combining data mining using PexFinder with PVX-based functional assays can facilitate the discovery of novel pathogen effector proteins. In principle, this strategy can be applied to a variety of eukaryotic plant pathogens, including oomycetes, fungi, and nematodes.

Algal Proteins↗

PubMed1992

Linear models for the prediction of stature from foot and boot dimensions.

Estimation of stature from the dimensions of foot or shoeprints has considerable forensic value in developing descriptions of suspects from evidence at the crime scene and in corroborating height estimates from witnesses. This study extends the findings of previous researchers by exploring linear models with and without gender and race indicators, and by validating the most promising models on a large, recently collected military database. Boot size and outsole dimensions are also examined as predictors of stature. The results of this study indicate that models containing both foot length and foot breadth are significantly better than those containing only foot length. Models with race/gender indicators also perform significantly better than do models without race/gender indicators. However, the difference in performance is slight, and the availability of reliable gender and race information in most forensic situations is uncertain. Analogous results were obtained for models utilizing boot size/width and outsole length/width, and in this study these variables performed nearly as well as the foot dimensions themselves. Although the adjusted R2 values for these models clearly reflect a strong relationship between foot/boot length and stature, individual 95% prediction limits for even the best models are +/- 86 mm (3.4 in.). This suggests that models estimating stature from foot/shoe-prints may be useful in the development of subject descriptions early in a case but, because of their imprecision, may not always be helpful in excluding individual suspects from consideration.

Anthropometry↗

PubMed2005

Synthetic ground truth for validation of brain tumor MRI segmentation.

Validation and method of comparison for segmentation of magnetic resonance images (MRI) presenting pathology is a challenging task due to the lack of reliable ground truth. We propose a new method for generating synthetic multi-modal 3D brain MRI with tumor and edema, along with the ground truth. Tumor mass effect is modeled using a biomechanical model, while tumor and edema infiltration is modeled as a reaction-diffusion process that is guided by a modified diffusion tensor MRI. We propose the use of warping and geodesic interpolation on the diffusion tensors to simulate the displacement and the destruction of the white matter fibers. We also model the process where the contrast agent tends to accumulate in cortical csf regions and active tumor regions to obtain contrast enhanced T1w MR image that appear realistic. The result is simulated multi-modal MRI with ground truth available as sets of probability maps. The system will be able to generate large sets of simulation images with tumors of varying size, shape and location, and will additionally generate infiltrated and deformed healthy tissue probabilities.

Algorithms↗

PubMed1999

Validating a decision support system for anti-epileptic drug treatment. Part I: initiating anti-epileptic drug treatment.

In this contribution the validation of a prototype decision support system that implements a model of expertise for initiating anti-epileptic drug treatment is described. Since domain experts were of the opinion that prescribing was a rather straightforward process we used only one expert neurologist for knowledge elicitation. To determine the correctness of the system we intended to compare the contents of the system's prescriptions with the majority decision of three neurologists. Because of a large variation in prescribing a majority decision could not be obtained in many cases. Even a Delphi procedure did not yield a majority decision in a large number of cases. Therefore a consensus meeting was organised to discuss cases where discrepancies remained. In the process the participating neurologists formulated prescription guidelines. These guidelines were used as a reference to determine the correctness of the prescriptions of both the system and of the neurologists. The acceptability of all prescriptions for each case was rated by the two neurologists who did not write a prescription for that case. From both comparisons it could be concluded that the system was at least as good in prescribing as individual neurologists.

Adolescent↗

PubMedDate not supplied

Evaluation of qsars for ecotoxicity: a method for assigning quality and confidence.

Validation of a quantitative structure-activity relationship (QSAR) is now considered as an integral part of its development. Assessment of the quality of a QSAR and the confidence that may be placed in predictions from it are vital to any validation procedure. A number of terms associated with the quality of a QSAR, confidence in that QSAR, or both may be quantified. These terms include the: (1) goodness of fit of the model (r2); (2) predictivity of the model (Q2); (3) stability of the model described as the difference between fit and predictivity (Dfp); (4) number of compounds used in the training set (Nc); (5) number of descriptors used in the model (Nd); (6) range of toxicity values (Tr); (7) number of mechanisms of toxic action covered by the training set (Nm), as well as two factors associated with the biological data-confidence associated with, (8) reproducibility of the data (Rconf) and (9) confidence in the source of the data (Sconf). While all these factors may influence the quality of, and/or confidence in a particular QSAR, each varies within different limits. To enable a quantitative assessment of quality and confidence in a QSAR, the terms deemed to be important were weighed and combined to create a Confidence Index (CI): ((r2)4 x 6) x ((Q2)4 x 6) x (ln(Nc/10)) x (Tr) x (Sconf)0.5 (ln(N2d + 2)) x (ln(N2m + 2)) x ((r2)4 x 6) - ((Q2)4 x 6) + 1) x (Rconf)

Algorithms↗

PubMed1993

The Australian Incident Monitoring Study. Crisis management--validation of an algorithm by analysis of 2000 incident reports.

Anaesthetists are called upon to manage complex life-threatening crises at a moment's notice. As there is evidence that this may require cognitive tasking beyond the information-processing capacity of the human brain, it was decided to try and develop a generic crisis management algorithm analogous to the "Phase I" immediate response routine used by airline pilots. Such an algorithm, based on the mnemonic "COVER ABCD, A SWIFT CHECK", was developed and refined over 3 meetings, each attended by 60-100 anaesthetists and aviation psychologists. It was validated against 1301 relevant incidents among the first 2000 incidents reported to the Australian Incident Monitoring Study. It proved sufficiently robust and safe to recommend its general use as an initial response to any incident or crisis which occurs when a patient is breathing gas from an anesthetic machine. It requires a limited knowledge base and is easily learnt and rehearsed during the anaesthetist's working day. It will provide a functional diagnosis in over 99% of cases and will correct 62% of the problems in 40-60 seconds. In the remaining 37% it will allow the anaesthetist to proceed with a "sub-algorithm", confident in the knowledge that some important step has not been missed. In just over 30% of incidents this will be for a problem familiar to all anaesthetists (e.g. laryngospasm, bradycardia); in just over 6% it will be for a less common, more complex, but finite, set of problems (3% cardiac arrest, 1% air embolism, 1% anaphylaxis, 1% for the remaining desaturations); in less than 1% diagnosis and correction will require a more complex checklist (e.g. for malignant hyperthermia, pneumothorax). The next stage, the development of specific sub-algorithms and a structured team approach for ongoing problems, is in progress.

Algorithms↗

PubMed2001

Validation of PD Adequest 2.0 for pediatric dialysis patients.

Kinetic modeling has proven to be a valuable tool for peritoneal dialysis (PD) prescription in adult PD patients. The clinical application of this procedure has rarely been studied in children. We therefore evaluated the PD Adequest 2.0 for Windows program (Baxter Healthcare Co., Deerfield, IL) as a prescription aid for the management of pediatric PD patients by comparing the measured and predicted PD clearances, total drain volumes, and net ultrafiltration in 34 children (15 males) (mean age 10.9 +/- 6.0 years) receiving long-term PD. In each case, a 4-h peritoneal equilibration test was conducted with a standardized test exchange volume of 1,100 ml/m2 BSA. A total of 43 24-h dialysate (plus urine in 12) collections were analyzed. The levels of agreement between measured and predicted values for weekly peritoneal and total urea Kt/V, weekly peritoneal and total creatinine clearance, daily drain volume, net ultrafiltration and daily peritoneal urea and creatinine mass removal were assessed with correlation coefficients (re) and Bland-Altman limits of agreement. The study revealed that there is a basic level of agreement between measured and modeled values for solute removal and total drain volume, with correlation coefficients ranging from 0.75 to 0.98. In contrast, the rc for net ultrafiltration was only 0.34. The majority (75%) of patients had modeled urea and creatinine clearances that were within 20% of their measured values. These data suggest that the PD Adequest 2.0 for Windows program can predict urea and creatinine clearances with reasonable accuracy in pediatric PD patients, making it a valuable resource in prescription management.

Child↗

PubMed2003

Validation and reproducibility of computerised cell-viability analysis of tissue slices.

BACKGROUND: The identification of live cells using membrane integrity dyes has become a frequently used technique, especially with articular cartilage and chondrocytes in situ where tissue slices are used to assess cell recovery as a function of location. The development of a reproducible computerised method of cell evaluation would eliminate many variables associated with manual counting and significantly reduce the amount of time required to evaluate experimental results. METHODS: To validate a custom computerised counting program, intra-person and inter-person cell counts of nine human evaluators (three groups - unskilled, novice, and experienced) were compared with repeated pixel counts of the custom program on 15 digitised images (in triplicate) of chondrocytes in situ stained with fluorescent dyes. RESULTS: Results indicated increased reproducibility with increased experience within evaluators [Intraclass Correlation Coefficient (ICC) range = 0.67 (unskilled) to 0.99 (experienced)] and between evaluators [ICC = 0.47 (unskilled), 0.85 (novice), 0.93 (experienced)]. The computer program had perfect reproducibility (ICC = 1.0). There was a significant relationship between the average of the experienced evaluators results and the custom program results (ICC = 0.77). CONCLUSIONS: This study demonstrated that increased experience in cell counting resulted in increased reproducibility both within and between human evaluators but confirmed that the computer program was the most reproducible. There was a good correlation between the intact cell recovery determined by the computer program and the experienced human evaluators. The results of this study showed that the computer counting program was a reproducible tool to evaluate intact cell recovery after use of membrane integrity dyes on chondrocytes in situ. This and the significant decrease in the time used to count the cells by the computer program advocate its use in future studies because it has significant advantages.

Animals↗

PubMed2002

Validity and accuracy of a risk calculator in predicting periodontal disease.

BACKGROUND: Research on the pathobiology of periodontal diseases has increased our knowledge of these diseases and is fostering a transition from the repair model to the medical or wellness model of periodontal care. Successful application of the wellness model depends on an accurate and valid assessment of disease risk, as well as institution of risk reduction as an integral part of prevention and treatment. A computer-based risk assessment tool has been developed. METHODS: The authors reviewed clinical records and radiographs of 523 subjects enrolled in the Veterans Affairs Dental Longitudinal Study to evaluate the validity of risk prediction using the computer-based tool. Data from baseline examinations was entered into the risk calculator, and a risk score on a scale from 1 (lowest risk) to 5 (highest risk) was calculated for each subject to predict periodontal deterioration. Actual periodontal status in terms of alveolar bone loss (determined from digitized radiographs) and tooth loss (determined from clinical records) was assessed at years 3, 9 and 15. The authors determined the statistical strength of the association between risk prediction and actual outcome. RESULTS: The risk scores were strong predictors of periodontal status, as measured by alveolar bone loss and loss of periodontally affected teeth. Risk scores consistently ranked risk score groups from least to most bone loss and tooth loss. Compared with a risk score of 2, the relative risk of tooth loss was 3.2 for a risk score of 3, 4.5 for a risk score of 4 and 10.6 for a risk score of 5. CONCLUSIONS AND PRACTICE IMPLICATIONS: Use of the risk assessment tool over time may result in more uniform and accurate periodontal clinical decision-making, improved oral health, reduction in the need for complex therapy, reduction in health care costs and a hastening of the transition from a repair model to a wellness model of care.

Alveolar Bone Loss↗

PubMed2003

Monte Carlo model of the Studsvik BNCT clinical beam: description and validation.

The neutron beam at the Studsvik facility for boron neutron capture therapy (BNCT) and the validation of the related computational model developed for the MCNP-4B Monte Carlo code are presented. Several measurements performed at the epithermal neutron port used for clinical trials have been made in order to validate the Monte Carlo computational model. The good general agreement between the MCNP calculations and the experimental results has provided an adequate check of the calculation procedure. In particular, at the nominal reactor power of 1 MW, the calculated in-air epithermal neutron flux in the energy interval between 0.4 eV-10 keV is 3.24 x 10(9) n cm(-2) s(-1) (+/- 1.2% 1 std. dev.) while the measured value is 3.30 x 10(9) n cm(-20 s(-1) (+/- 5.0% 1 std. dev.). Furthermore, the calculated in-phantom thermal neutron flux, equal to 6.43 x 10(9) n cm(-2) s(-1) (+/- 1.0% 1 std. dev.), and the corresponding measured value of 6.33 X 10(9) n cm(-2) s(-1) (+/- 5.3% 1 std. dev.) agree within their respective uncertainties. The only statistically significant disagreement is a discrepancy of 39% between the MCNP calculations of the in-air photon kerma and the corresponding experimental value. Despite this, a quite acceptable overall in-phantom beam performance was obtained, with a maximum value of the therapeutic ratio (the ratio between the local tumor dose and the maximum healthy tissue dose) equal to 6.7. The described MCNP model of the Studsvik facility has been deemed adequate to evaluate further improvements in the beam design as well as to plan experimental work.

Boron Neutron Capture Therapy↗

PubMed2003

Validating a computerized neuropsychological test battery for mixed ethnic lupus patients.

Patients with systemic lupus erythematosus (SLE) often show cognitive impairment on traditional neuropsychological tests; however, many of these tests are unsuitable for use with mixed ethnic populations. Computer-administered cognitive tests are promising, but have not been validated against traditional tests or with predominantly Hispanic samples. We gave 67 lupus patients a computer-administered test battery (Automated Neuropsychological Assessment Metrics--ANAM) and a battery of traditional neuropsychological tests. The two batteries were compared using correlation and multiple regression analyses. All patients were fluent in English, 54% were Hispanic and 13% were bilingual. Non-Hispanic patients were predominantly European American (37%). About 80% of patients were rated as impaired on traditional tests. Hispanics were younger, had less education and more current SLE disease activity than non-Hispanics; but did not differ in lifetime SLE-related organ damage or current steroid use. Hispanics and younger patients were more impaired on many of the traditional tests, while ANAM was not affected by Hispanic ethnicity or education. ANAM tests were moderately correlated with analogous traditional tests. Age and selected ANAM scores accounted for about 60% of the variance in the traditional battery. These results replicate the high prevalence of cognitive deficits in SLE found by others and suggest that computer-administered tests like ANAM may be useful for assessment of cognitive impairment in mixed-ethnic samples. Confounding variables such as age, education, English language fluency and prior experience with tests were identified and need to be controlled statistically or with comparison groups in future studies.

Adult↗

PubMed2003

Anterior cruciate ligament tunnel placement: Comparison of insertion site anatomy with the guidelines of a computer-assisted surgical system.

PURPOSE: With the development of computer-assisted surgery (CAS) systems, the surgeon's ability to operate a CAS planning station will become essential. For example, default parameters in computed tomographic (CT) data are being used to place tunnels in anterior cruciate ligament (ACL) reconstruction. The goal of this study was to compare the location of the insertion sites in ACL reconstruction anatomically, via roentgenographic images and via CT scan data and to validate these tunnel placement parameters. TYPE OF STUDY: Cadaveric analysis. METHODS: Eight human cadaveric knees were marked with 6 copper wires 1 mm in diameter around the circumference of the insertions of the ACL. Using lateral roentgenograms and CT scans that were subsequently transferred to the CAS planning station, the tunnel locations were determined. These were based on a distance from the back of the condyle (location A) and from the roof of the notch (location B) on the femur and on a distance posterior from the tuberosity to the posterior margin along the tibial plateau, which is set as the CAS planning station's default. Locations according to roentgenograms and CT scans were then compared and the accuracy of the CAS planning station was assessed. RESULTS: Comparison of roentgenograms and CT revealed a femoral insertion at 27.5% +/- 3.2% and 26.9% +/- 3.5% (roentgenograms) and 26.6% +/- 1.9% and 26.3% +/- 2.4% (CT), respectively. The CAS planning station provided a tunnel location that was 1.3 +/- 1.0 mm (0.3 to 2.5 mm) away from the actual femoral ACL insertion. The tibial tunnel was placed according to the copper wire markers and was found to be at 46.2% +/- 2.8% (roentgenograms) and 45.4% +/- 2.1% (CT). No statistical differences between position in CT and roentgenograms could be detected (P >.05). CONCLUSIONS: The compared methodologies showed similar locations of the ACL insertions, assuring accurate preoperative planning with the CAS system. However, the CAS system requires adjustment to each individual knee anatomy.

Aged↗

PubMed2003

Monte Carlo model of the Elekta SLiplus accelerator: validation of a new MLC component module in BEAM for a 6 MV beam.

A new component module (CM), called MLCE, has been implemented in the BEAM program. The CM takes into account the particular 'tongue-and-groove' design of the Elekta multi-leaf collimator (MLC) and the air gap between the leaves. The model was validated by two series of measurements and simulations. The first benchmarking series focuses on the interleaf leakage and the intraleaf transmission. The measurement showed a total transmission through the MLC of 1.42% of the open field dose. Two Monte Carlo (MC) simulations were made, the first with the new CM MLCE (inclusive of air gap) and the second with the CM MLCQ (exclusive of air gap), which is available in the BEAM distribution. When the air gap between the leaves was determined by varying the parameters of the leaf geometry within tolerance limits on the technical drawing, the total measured transmission of 1.42% was well reproduced by the CM MLCE. In contrast, MC simulations with MLCQ showed that the transmission through the MLC calculated without the interleaf leakage is only 44% of the total transmitted radiation. The relevance of the detailed MLC modelling was demonstrated also by studying the 'adjacent' tongue-and-groove effect, where two adjacent (not opposing) leaves are complementary, opened or closed. The two complementary leaf settings were simulated both with the CM MLCE and MLCQ. A comparison with measurements was made. In regions covered by two or more leaves, the dose increased by 14% for two leaves and by 40% for more than two leaves when the interleaf leakage was included in the transmission. The tongue-and-groove effect was perfectly reproduced by the MLCE module.

Algorithms↗

PubMed2002

Dynamic characterization of the molecular events during in vitro epidermal wound healing.

The aim of this study was to characterize some of the molecular events stimulated in vitro in response to injury within a confluent culture of normal epidermal keratinocytes as a model to understand the mechanisms of wound healing. To this end, an original device was developed specifically designed to perform calibrated injuries of great lengths within mono-stratified or pluri-stratified keratinocyte cultures. The experiments performed in this study validate this device as an appropriate tool for studying epidermal wound healing; this is because it performs mechanical injuries that stimulate the expression of multiple healing markers also known to be upregulated during wound healing in vivo (growth factors, cytokines, proteinases, extracellular matrix proteins). Using this device, it was demonstrated in human keratinocytes: mechanical injuries (i) immediately stimulate the tyrosine phosphorylation of numerous cellular proteins; (ii) induce molecular cascades leading to the activation of p21ras, mitogen-activated protein kinases, extracellular signal-regulated kinases 1/2, c-Jun NH2 terminal kinase, and p38 mitogen-activated protein kinase; and (iii) increase the phosphorylation of their respective substrates, c-jun and activator transcription factor 1. Wounding of these cells also results in increases in the DNA binding activities of several jun/fos activator protein-1 transcription factor complexes. It is important to note that the development of an appropriate wounding system was essential for performing this study, as use of a classical wounding procedure did not enable the detection of the biologic parameters reported above. In conclusion, these data indicate that using the appropriate system, it is possible to identify the signaling pathways activated in normal human keratinocyte cells after injury. In this study, it was shown that the mitogen-activated protein kinase pathways and activator protein-1 are stimulated in response to physical injury, and may be involved in regulating the expression of healing markers.

Cells, Cultured↗

PubMed2003

Reliability of the ICRP's dose coefficients for members of the public. III. Plutonium as a case study of uncertainties in the systemic biokinetics of radionuclides.

This paper is a case study of the validity of different data sources and modelling approaches commonly used to build biokinetic models for radionuclides. The paper examines the basis and apparent predictive accuracy of each of the biokinetic models for Pu used over the years by the International Commission on Radiological Protection (ICRP), in view of recent improvements in the database. The results of this study and similar retrospective studies for other elements suggest the following five points. (1) Extrapolation of biokinetic data from laboratory animals to man is particularly uncertain for the liver due to qualitative differences among species in the handling of many elements by this organ. (2) As a 'default' approach to biokinetic modelling or model assessment, biokinetic data for unhealthy human subjects should be given higher weight than information extrapolated across animal species or chemical families, but there are counter-examples. (3) Little confidence can be placed in biokinetic model predictions for long times after exposure based solely on curve fits to short-term biokinetic data. (4) Bioassay and dosimetry models for a radionuclide should not be developed separately. (5) Where feasible, the systemic biokinetic model for a radionuclide should be developed within a physiologically realistic model structure, because this allows biokinetic data from experimental studies to be supplemented with physiological information, provides a basis for extrapolation of data across animals species or chemical families, results in models that can be used for both bioassay interpretation and dosimetry, and provides a logical basis for extrapolation of data to subgroups of the population (e.g., various ages) or to times outside the period of observation.

Body Burden↗