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PubMedDate not supplied

Actigraphic assessment of sleep in insomnia: application of the Actigraph Data Analysis Software (ADAS).

The usefulness of the actigraph methodology has been demonstrated in normal individuals. However, the validity of actigraphy has been questioned in insomnia patients because of the considerable measurement error that has been reported between actigraphy (ACT) and polysomnography (PSG). Two independent investigations have reported errors of 48 and 49 min in total sleep time between ACT and PSG. With a new scoring method called the Actigraph Data Analysis Software, a reanalysis of one of these studies was conducted. Based on this reanalysis, we have obtained a measurement error of only 25 min between the two methods. This finding may be an indication of the advantage of this new scoring method. A strong correlation coefficient (r = 0.82, p < 0.0001) was noted between ACT and PSG for total sleep time, thus suggesting a high degree of accuracy of the actigraph methodology in assessing the sleep/wake profile of insomniacs.

Arousal↗
PubMed2006

PedGenie: an analysis approach for genetic association testing in extended pedigrees and genealogies of arbitrary size.

BACKGROUND: We present a general approach to perform association analyses in pedigrees of arbitrary size and structure, which also allows for a mixture of pedigree members and independent individuals to be analyzed together, to test genetic markers and qualitative or quantitative traits. Our software, PedGenie, uses Monte Carlo significance testing to provide a valid test for related individuals that can be applied to any test statistic, including transmission disequilibrium statistics. Single locus at a time, composite genotype tests, and haplotype analyses may all be performed. We illustrate the validity and functionality of PedGenie using simulated and real data sets. For the real data set, we evaluated the role of two tagging-single nucleotide polymorphisms (tSNPs) in the DNA repair gene, NBS1, and their association with female breast cancer in 462 cases and 572 controls selected to be BRCA1/2 mutation negative from 139 high-risk Utah breast cancer families. RESULTS: The results from PedGenie were shown to be valid both for accurate p-value calculations and consideration of pedigree structure in the simulated data set. A nominally significant association with breast cancer was observed with the NBS1 tSNP rs709816 for carriage of the rare allele (OR = 1.61, 95% CI = 1.10-2.35, p = 0.019). CONCLUSION: PedGenie is a flexible and valid statistical tool that is intuitively simple to understand, makes efficient use of all the data available from pedigrees without requiring trimming, and is flexible to the types of tests to which it can be applied. Further, our analyses of real data indicate NBS1 may play a role in the genetic etiology of heritable breast cancer.

Biomarkers, Tumor↗
PubMed2003

A compartmental pharmacokinetic model of cyclosporin and its predictive performance after Bayesian estimation in kidney and simultaneous pancreas-kidney transplant recipients.

BACKGROUND: Therapeutic drug monitoring of cyclosporin A (CsA) is an obvious necessity because of its unpredictable absorption and narrow therapeutic window. The use of limited sampling models (LSMs) has improved the estimation of the systemic exposure [area under curve (AUC)] compared with C(0h) monitoring, but these equations are rigid and not reliable in patients with an abnormal absorption profile. We developed and validated a limited sampling (t=0, 2 and 3 h) strategy, based on a compartmental population pharmacokinetic (PK) model for CsA after kidney transplantation alone (KTA) and simultaneous pancreas-kidney transplant (SPKT) recipients, a group of patients with unpredictable absorption kinetics. METHODS: A two-compartment model with lag time and first-order absorption was calculated using a PK software package from data of 20 KTA and SPKT recipients and validated prospectively in 20 KTA and 20 SPKT recipients. Calculated population PK parameters were individualized for each of the remaining 40 patients based on their CsA dosing and on one or a combination of measured CsA blood concentrations using the Bayesian fitting method. AUCs were calculated from individualized PK parameters. AUCs were also calculated using previously published LSMs. Relationships between AUCs calculated by the models and the 'golden standard' AUC (trapezoidal rule) were investigated by Pearson correlation test. RESULTS AND CONCLUSIONS: A population two-compartment model is presented to reliably estimate the CsA AUC in KTA and SPKT recipients. The performance of the model to estimate the AUC is comparable to the performance of two published LSMs in KTA patients, but markedly better in SPKT patients. Combined with Bayesian fitting, the model is very flexible since sampling times are not rigid and can be varied as long as dosing and sampling times are recorded accurately. The model has already proven to be clinically useful and is currently used to further investigate CsA in an integrated pharmacokinetic/pharmacodynamic model.

Area Under Curve↗
PubMed2002

[The Internet as a source for information retrieval. Example: soft tissue sarcoma].

INTRODUCTION: Due to increasing availability, easier access, and rapid growth of information, the Internet has become an important source of medical information. We analyzed the value of Internet sites and the content of their medical information for physicians and patients using the example "soft tissue sarcoma." METHODS: Sixteen German and English Internet search engines were used to evaluate the retrieved internet sites regarding their target group, publisher, contents, and topicality. RESULTS: The majority of retrieved websites were in English compared to significantly fewer in German. The content of information was more valuable for patients and physicians on the English websites compared to the German ones. Even if many of the evaluated websites originated from medical organizations or universities, the amount of information was limited and often not up to date. CONCLUSION: Information on the web is widespread, but for special queries too limited and difficult to identify. An improvement of available websites is needed, especially those maintained by universities and nonprofit medical organizations. The retrieval software should be optimized to ease identification of information, which should be validated by a recognized standard.

Humans↗
PubMed1999

Digital image capture and automated analysis of posterior capsular opacification.

PURPOSE: To develop and validate a digital imaging and analysis technique for assessing the extent of posterior capsular opacification after cataract surgery. METHODS: Retroillumination images of the posterior capsule were obtained by using a digital camera mounted on a slit lamp. The images were analyzed using an available image analysis software program. The image acquisition and analysis techniques were tested for face validity, reproducibility, and the ability to detect progression of capsular opacity over time. RESULTS: Digital retroillumination images were obtained without patient discomfort. Automated analysis of images correlated well with clinical grading both at slit lamp examination and when looking at the images themselves (Spearman's correlation coefficient >0.7). Analysis of images taken at different times showed high reproducibility (intraclass correlation >0.9), and the system was able to identify progression of capsular opacity over a 2-year period with a mean increase of 15.8% in progressors versus an increase of 0.6% in nonprogressors (P < 0.05). CONCLUSIONS: Digital retroillumination images of the posterior capsule can be obtained reliably, and automated analyses correlate well with clinical assessment. The system presented here uses commercially available instruments and software, and it is practical for use in longitudinal studies of posterior capsule opacification. It is reliable, easy to use, and can detect small changes in the percentage area covered by posterior capsule opacification over time.

Cataract↗
PubMed2024

The Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry.

Donald Hunt has made seminal contributions to the fields of proteomics, immunology, epigenetics, and glycobiology. The foundation of every important work to come out of the Hunt Laboratory is de novo peptide sequencing. For decades, he taught hundreds of students, postdocs, engineers, and scientists to directly interpret mass spectral data. To honor his legacy and ensure that the art of de novo sequencing is not lost, we have adapted his teaching materials into "The Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry". In addition to the de novo sequencing tutorials, we present two freely available software tools that facilitate manual interpretation of mass spectra and validation of search results. The first, "Hunt Lab Peptide Fragment Calculator", calculates precursor and fragment mass-to-charge ratios for any peptide. The second program, "Predator Protein Fragment Calculator", was inspired in part by the fragment calculator developed in the Hunt Lab. Its capabilities are enhanced to facilitate interpretation of mass spectral data derived from intact proteins. We hope that the combination of these educational tools will continue to benefit students and researchers by empowering them to interpret data on their own.

Tandem Mass Spectrometry↗
PubMed2004

Three-dimensional modeling and animation of two carpal bones: a technique.

The objectives of this study were to (a). create 3D reconstructions of two carpal bones from single CT data sets and animate these bones with experimental in vitro motion data collected during dynamic loading of the wrist joint, (b). develop a technique to calculate the minimum interbone distance between the two carpal bones, and (c). validate the interbone distance calculation process. This method utilized commercial software to create the animations and an in-house program to interface with three-dimensional CAD software to calculate the minimum distance between the irregular geometries of the bones. This interbone minimum distance provides quantitative information regarding the motion of the bones studied and may help to understand and quantify the effects of ligamentous injury.

Carpal Bones↗
PubMed2000

Use of rubber dam and irrigant selection in UK general dental practice.

AIM: To evaluate factors which influence rubber dam use and irrigant selection in UK National Health Service (NHS) endodontics. METHODOLOGY: A postal survey was conducted amongst two age cohorts of dentists, representing all of the 1970-73 (older) and 1990-93 (younger) graduates of two northern English dental schools (n = 643). Key and supplementary questions were posed on levels of rubber dam use, irrigant selection, and factors influencing practice in NHS endodontics. After manual checking, validated (dual) entry of responses was made to a flat ASCII data file before analysis with SPSS software. The threshold for statistical significance was set at the 95% probability level. RESULTS: Eighty-five per cent of the valid sample responded to the questionnaire. Regardless of age and qualifying school, less than one-fifth of dentists always or frequently used rubber dam, whilst 60% never used it. Qualifying school had a significant influence on rubber dam use, whilst age had a variable influence. Major disincentives to the use of rubber dam included the perception that patients do not like it, that the NHS fee was inadequate to justify its use, that it took too long to apply, and that dentists had received inadequate training. Frequent users of rubber dam were significantly less likely to cite these disincentives than nonusers. Overall, local anaesthetic solution was the most common endodontic irrigant. Irrigant choice was strongly linked to rubber dam use, and to graduation cohort. Seventy-one per cent of rubber dam users irrigated with sodium hypochlorite, compared with only 38% of nonusers. This pattern was reversed for local anaesthetic irrigation. Younger graduates were significantly more likely to irrigate with local anaesthetic solution than their older counterparts, and the younger graduates of one school showed a highly significant increase in the use of chlorhexidine. CONCLUSIONS: 1) The majority of UK Health Service dentists never use rubber dam isolation in endodontic treatment. 2) Qualifying school has a significant impact on rubber dam use, and irrigant selection. 3) Use of rubber dam has a significant association with irrigant choice in endodontics.

Age Factors↗
PubMed1989

Legal issues associated with pharmacokinetic software.

Legal issues associated with the use of pharmacokinetic computer software are discussed. One issue involves the physician's reliance on the pharmacist, as a drug therapy expert, to provide consultation on drug dosages. Another issue is the problem of liability associated with the software and how this relates to the physician, the pharmacist, and those who designed, manufactured, and sold the software. The legal concept of negligence as it relates to medical computer software is discussed. Although the programmer and the manufacturer are responsible for verifying that the program does what it purports to do, the user must exercise due care in identifying any program limitations that might influence the accuracy of a consultation. Clinical perspective, effective validation techniques, and critical selection will help to ensure that pharmacokinetic computer software is developed, purchased, and used safely and effectively.

Drug Therapy, Computer-Assisted↗
PubMed2005

Assessment of radiofrequency exposure from cellular telephone daily use in an epidemiological study: German Validation study of the international case-control study of cancers of the brain--INTERPHONE-Study.

OBJECTIVE: The objective of the study is to validate self-reported cellular phone use information by comparing it with the cumulative emitted power and duration of calls measured by software-modified cellular phones (SMP). The information was obtained using a questionnaire developed for the international case-control study on the risk of the use of mobile phones in tumours of the brain or salivary gland (INTERPHONE-study). METHOD: The study was conducted in Bielefeld, Germany. Volunteers were asked to use SMPs instead of their own cellular phones for a period of 1 month. The SMP recorded the power emitted by the mobile phone handset during each base station contact. Information on cellular phone use for the same time period from traffic records of the network providers and from face-to-face interviews with the participants 3 months after the SMP use was assessed. Pearson's correlation coefficients and linear regression models were used to analyse the association between information from the interview and from the SMP. RESULTS: In total, 1757 personal mobile phone calls were recorded for 45 persons by SMP and traffic records. The correlation between the self-reported information about the number and the duration of calls with the cumulative power of calls was 0.50 (P<0.01) and 0.48 (P<0.01), respectively. Almost 23% of the variance of the cumulative power was explained by either the number or the cumulative duration of calls. After inclusion of possible confounding factors in the regression model, the variance increased to 26%. Minor confounding factors were "network provider", "contract form", and "cellular phone model". DISCUSSION: The number of calls alone is a sufficient parameter to estimate the cumulative power emitted by the handset of a cellular telephone. The cumulative power emitted by these phones is only associated with number of calls but not with possible confounding factors. Using the mobile phone while driving, mainly in cities, or mainly in rural areas is not associated with the recorded cumulative power in the SMP.

Automation↗
PubMed2000

Predictive accuracy of population viability analysis in conservation biology.

Population viability analysis (PVA) is widely applied in conservation biology to predict extinction risks for threatened species and to compare alternative options for their management. It can also be used as a basis for listing species as endangered under World Conservation Union criteria. However, there is considerable scepticism regarding the predictive accuracy of PVA, mainly because of a lack of validation in real systems. Here we conducted a retrospective test of PVA based on 21 long-term ecological studies--the first comprehensive and replicated evaluation of the predictive powers of PVA. Parameters were estimated from the first half of each data set and the second half was used to evaluate the performance of the model. Contrary to recent criticisms, we found that PVA predictions were surprisingly accurate. The risk of population decline closely matched observed outcomes, there was no significant bias, and population size projections did not differ significantly from reality. Furthermore, the predictions of the five PVA software packages were highly concordant. We conclude that PVA is a valid and sufficiently accurate tool for categorizing and managing endangered species.

Animals↗
PubMed2005

Doelan: a solution for quality control monitoring of microarray production.

SUMMARY: Doelan is an automated tool designed to monitor the quality of DNA microarray production. The software executes a series of quality control tests on hybridizations to validate batches of chips. The reports generated by Doelan should help microarray platforms aiming at quality labels, such as ISO 9001 certification. The Doelan application is written in Java and works with a plug-in system that allows everyone to add custom validation tests. AVAILABILITY: The Doelan application is distributed under the GNU General Public License at http://transcriptome.ens.fr/doelan/

Algorithms↗
PubMedDate not supplied

[Database application for information on post-surgical evolution after functional neurosurgery].

INTRODUCTION: A series of quantitative scales have been established internationally to evaluate the functional state of patients affected by movement disorders, such as Parkinson s disease. The values of these parameters offered by each patient, measured at different moments during his or her illness, allow us to conduct studies into their evolution as well as perform statistical studies about the casuistics. AIM. To provide a tool that enables us to study this vast amount of material in an efficient, sure and, above all, automated manner. Materials and methods. We selected the most interesting variables from the international protocols. We also designed and developed a database application for use under the Windows environment using Delphi 3.0 language and compiler and Structured Query Language. RESULTS: We designed, developed and validated a database system so as to be able to handle automatically the information on the clinical evolution of patients who had undergone functional neurosurgery. This system not only enables us to collect all relevant pre and post surgical information but also allows fast searches and selection, data processing using descriptive statistical techniques and the exportation of the data in a standard format. The system, which also allows final double blind clinical evaluation of each patient to be performed, has been used successfully in the Movement Disorders Clinic at the CIREN for over three years. CONCLUSIONS: This system allows for a considerable saving in the amount of time and effort needed for the post surgical evolution of patients, while also increasing the reliability of the results obtained.

Databases, Factual↗
PubMed2006

Computer-assisted detection for CT colonography: external validation.

AIM: To externally validate a computer-assisted detection (CAD) system for computed tomography (CT) colonography, using data from a single centre uninvolved with the software development. MATERIALS AND METHODS: Twenty-five multi-detector CT colonography examinations of patients with validated polyps accumulated at a single centre were examined by two readers who used endoscopic and histopathological data to identify polyp coordinates. A CAD system that had been developed using data from elsewhere, and had not previously encountered the present data, was then applied to the data at sphericity filter settings of 0.75 and 0.50 and identified potential polyps. True-positive, false-negative, and false-positive counts were determined by comparison with the known polyp coordinates. RESULTS: Twenty-five patients had 57 polyps, median size 6mm (range 1-15mm). Per-patient sensitivity for the CAD system was 96% (24 of 25). The CAD system detected 44 (77%) polyps at sphericity setting 0.75 and 49 (86%) polyps at sphericity 0.50: the additional five polyps detected all measured 5mm or less. Sphericity of 0.75 resulted in a median of 10 (one to 34) easily dismissed false-positive prompts per patient and a median of 4 (zero to 15) that needed three-dimensional rendering before dismissal. This rose to 32 (16 to 99) and 11 (three to 35), respectively, at sphericity 0.5. CONCLUSIONS: A per-patient sensitivity of 96% was found for the CAD system (in patients with a median polyp diameter of 6mm) using external validation, a more stringent test than either internal cross-validation or temporal validation. Decreasing sphericity increases sensitivity for small polyps at the expense of decreased specificity.

Colonic Polyps↗
PubMed2005

Evaluation and further development of EASE model 2.0.

EASE (Estimation and Assessment of Substance Exposure) is a general model that may be used to predict workplace exposure to a wide range of substances hazardous to health. First developed in the early 1990s, it is now in its second Windows version. This paper provides a critical assessment of the utility and performance of the EASE model, and on the basis of this review, recommendations for the structure of a revised model are outlined. Twenty-seven stakeholders were interviewed about their previous use of EASE, perceived advantages and limitations of the model and suggestions for improvement. A subset of stakeholders was contacted on a second occasion to determine their views on the preferred outputs for an ideal exposure assessment model. Overall, stakeholders felt that the model should be updated to provide more accurate and precise exposure assessments. However, users also expressed the view that the simplicity and usability of the software model should not be compromised. Six studies investigating the validity of the inhalation exposure assessment section of EASE were identified. These showed that the model generally either predicted close to the measured exposures or overestimated exposure; though performance was highly variable. Two studies investigated the validity of the dermal exposure assessment and found that EASE produced considerable overestimates of actual dermal exposure (the amount of a substance that actually lands on the skin). A conceptual model of exposure was developed to investigate whether the structure of the EASE model is appropriate. Although EASE has a number of characteristics that describe exposure, it is a greatly simplified model and does not include all the important exposure determinants. More importantly, EASE can produce estimates of exposure that are ambiguous or incomplete. Our conceptual model may provide a rational basis for developing an improved version of EASE but further consultation is needed to decide the purpose and intended use of any successor to EASE.

Air Pollutants, Occupational↗
PubMed2003

Guideline validation in multiple trauma care through business process modeling.

Clinical guidelines can improve the quality of care in multiple trauma. In our Department of Trauma Surgery a specific guideline is available paper-based as a set of flowcharts. This format is appropriate for the use by experienced physicians but insufficient for electronic support of learning, workflow and process optimization. A formal and logically consistent version represented with a standardized meta-model is necessary for automatic processing. In our project we transferred the paper-based into an electronic format and analyzed the structure with respect to formal errors. Several errors were detected in seven error categories. The errors were corrected to reach a formally and logically consistent process model. In a second step the clinical content of the guideline was revised interactively using a process-modeling tool. Our study reveals that guideline development should be assisted by process modeling tools, which check the content in comparison to a meta-model. The meta-model itself could support the domain experts in formulating their knowledge systematically. To assure sustainability of guideline development a representation independent of specific applications or specific provider is necessary. Then, clinical guidelines could be used for eLearning, process optimization and workflow management additionally.

Humans↗
PubMedDate not supplied

Finite element modeling of diffusion and partitioning in biological systems: the infinite composite medium problem.

Four methods are proposed for modeling diffusion in heterogeneous media where diffusion and partition coefficients take on differing values in each subregion. The exercise was conducted to validate finite element modeling (FEM) procedures in anticipation of modeling drug diffusion with regional partitioning into ocular tissue, though the approach can be useful for other organs, or for modeling diffusion in laminate devices. Partitioning creates a discontinuous value in the dependent variable (concentration) at an intertissue boundary that is not easily handled by available general-purpose FEM codes, which allow for only one value at each node. The discontinuity is handled using a transformation on the dependent variable based upon the region-specific partition coefficient. Methods were evaluated by their ability to reproduce a known exact result, for the problem of the infinite composite medium (Crank, J. The Mathematics of Diffusion, 2nd ed. New York: Oxford University Press, 1975, pp. 38-39.). The most physically intuitive method is based upon the concept of chemical potential, which is continuous across an interphase boundary (method III). This method makes the equation of the dependent variable highly nonlinear. This can be linearized easily by a change of variables (method IV). Results are also given for a one-dimensional problem simulating bolus injection into the vitreous, predicting time disposition of drug in vitreous and retina.

Biological Transport, Active↗
PubMed2003

Validation of intensity modulation on a commercial treatment planning system.

For two years now, a study on intensity modulated radiotherapy (IMRT) has been in progress at the Antoine Lacassagne Hospital Center for Cancer Therapy (in Nice) in collaboration with the University of Nice-Sophia Antipolis. The kind of intensity modulation that was used is the "step and shoot" technique in which the modulated beam is created both by adding andjoining elementary fields. Before carrying out clinical tests, several problems regarding the production of modulated beams has to be mastered. The current developments of our study enable us to dosimetrically produce (in water phantom and in the PMMA phantom) complexmodulated whose segmentation was calculated by one commercial treatment planning system (TPS). Nevertheless, we showed and studied some critical discrepancies between standard clinical calculations and the calculations using field segmentation. We showed that with nonoptimal conditions of segmentation the discrepancies, which are due to the type of algorithm used, could bring about significant errors inside the field of up to 10% of maximum dose. Another point of our study is the quantification and resolution of differences between measurements and calculations due to the internal segmentation of calculated modulated fields and their realization on Linac. Once again, in none optimal conditions of segmentation and inside the field we obtained discrepancies up to 20% of maximum dose between calculations using field segmentation and measurements. That was mainly due to the tongue and groove effect and penumbra phenomena. This study allows us to show that the discrepancies between segmentation calculations and standard clinical calculations should be solved by the use of penumbra models during segmentation calculations. We will introduce both the study and its near-future perspectives.

Algorithms↗