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PubMed1999

DOSE3D: EGS4 Monte Carlo code-based software for internal radionuclide dosimetry.

UNLABELLED: MIRDOSE3 software is currently the main tool available in clinical practice to evaluate absorbed dose in nuclear medicine. Because MIRDOSE3 provides dosimetric parameters for specific anatomic models that cannot be modified by the user, it cannot be used to obtain information concerning metastases or to consider patients whose anatomy differs significantly from that of the standard models. METHODS: To address some of these inconveniences, we developed an original program based on the EGS4 Monte Carlo code, DOSE3D, which calculates dosimetric parameters for anthropomorphic phantoms defined with combinatorial geometry. DOSE3D allows the user to add spheres within the phantom for simulating tumors, to change the shape of one or more organs and, for organs defined by pair, to calculate individual dosimetric parameters for each organ. The program was validated for 131I and 99mTc by calculating S values for the Medical Internal Radiation Dose (MIRD) adult male phantom and comparing these results with data provided by MIRDOSE3. Moreover, two studies were performed to illustrate DOSE3D features. The first one concerned the evaluation of the individual influence of two bone metastases (located in the pelvis and in the lower spine and containing 131I) on testes in terms of S values compared with the influence on testes of other source organs (kidneys, liver, lungs, spleen, thyroid gland and urinary bladder contents). The second study determined the differences of S values between right and left lungs and right and left kidneys when 131I is contained in the liver. RESULTS: The DOSE3D S values were on average within 20% of the MIRDOSE3 results for both radionuclides. Regarding the bone metastases study, S(testes<--metastases) and S(testes<--any source organs) were of the same order of magnitude. In the second study, the S values ratio between right and left organs was 7.7 for the lungs and 5.2 for the kidneys. CONCLUSION: The agreement between DOSE3D and MIRDOSE3 results for most organs shows the validity of DOSE3D. The presented examples of calculation show that DOSE3D could provide additional data to dosimetric parameters given by MIRDOSE3 for a more patient-specific dosimetric approach.

Adult↗
PubMed2005

Documenting drug-related problems with personal digital assistants in a multisite health system.

PURPOSE: A scalable, multiuser, personal digital assistant (PDA)-based documentation tool for pharmacist collection of data on drug-related problems (DRPs) is described. SUMMARY: A PDA-based tool for documenting DRPs and pharmacist interventions was developed with database software. Data fields were based on the pharmaceutical care model. PDA synchronization stations were configured to transmit encrypted data from three hospital sites to a central server. Pharmacists in a multisite health care organization were trained to use the documentation tool. Data were analyzed with commercially available software. Users' opinions about the tool were solicited in a survey. Twenty-eight PDAs containing a 15-field database were issued to 39 pharmacists in 31 service areas. Data were successfully transmitted from all hospital sites over the existing corporate local area network. During a two-month period, 5084 DRPs were documented; 90% of them were resolved at the time of data entry. The most frequent types of DRPs were the need to add a drug (31%) and the ordering of an unnecessary drug (15%). Most pharmacists reported that the tool was easy to use, was well integrated with the workflow, and required less than 30 minutes per day for documenting DRPs. CONCLUSION: A PDA-based documentation tool was successfully used in a multisite health care organization to collect data on DRPs and document pharmacist interventions.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Whole genome SNP arrays using DNA derived from formalin-fixed, paraffin-embedded ovarian tumor tissue.

Array-based genotyping platforms, such as the Affymetrix mapping array, have been validated as reliable methods for obtaining high-resolution copy number and allele status information when using DNA derived from fresh tissue sources. However, the suitability of such systems for the examination of DNA derived from formalin-fixed, paraffin-embedded (FFPE) tissues has not been tested. Therefore, we analyzed DNA derived from five matching fresh frozen and FFPE ovarian tumors for gene copy number changes and loss of heterozygosity using the Affymetrix GeneChip Human Mapping 10 K Array Xba 131. The data was analyzed using Affymetrix proprietary software, GeneChip DNA Analysis Software, and Chromosome Copy Number Tool. The average SNP call rate (rate of successful genotype identification) of the fresh samples was 89.44% (range 78.72-96.22%, median 92.72%) and was only slightly lower for the matching FFPE samples at 83.48% (range 76.93-93.17%, median 82.60%). The average concordance (rate of agreement between successful genotype calls) between the fresh and matching FFPE samples was 97.06% (range 92.70-99.41%, median 97.52%). Loss of heterozygosity (LOH) profiles of the fresh and FFPE samples were essentially identical across all chromosomes. Copy number data was also comparable, although the quantification of copy number changes appears overstated in the FFPE samples. In conclusion, we have shown that it is possible to achieve high-performance outcomes using FFPE-derived DNA in the Affymetrix 10 K mapping array. This advance will open up vast archival tissue resources to high-resolution genetic analysis and unlock a wealth of biological information.

DNA↗
PubMed2005

Analytical technique for quantification of selected resorbable calcium phosphate bone void fillers with the use of polarized-light microscopy.

Synthetic calcium phosphate bone void fillers promote varying rates of bone formation and material resorption depending on chemistry, porosity, pore structure, and implant site. The objective of this study was to quantify the resorption of a novel ultraporous beta-tricalcium phosphate cancellous bone void filler with simultaneous quantification of bone formation in a canine humerus model. Potential measurement error involved in conventional histomorphometry using Von Kossa stains inspired the development of a new technique. This technique utilizes bright-field and polarized-light microscopy in conjunction with image analysis software, allowing more accurate histomorphometry. This technique was validated with two separate controlled experiments. Scanning electron microscopy further supported the results. The findings suggest that the use of polarized-light microscopy combined with image analysis software can be an effective tool in simultaneously quantifying calcium phosphate resorption and bone formation.

Animals↗
PubMed2005

Rapid enrichment of bioactive milk proteins and iterative, consolidated protein identification by multidimensional protein identification technology.

Direct injection of complex protein mixtures, e.g. those derived from crude biological fluids, is often incompatible with conventional LC supports, because of column clogging and rapid deterioration of chromatographic performance. In this paper, we report the use of restricted access media to rapidly enrich and fractionate human breast milk. This resin, combining size exclusion and anion exchange functionalities, yielded a fraction enriched in soluble CD14 and showing specific sCD14-dependant activity. This fraction was split into five aliquots, which were individually characterized using multidimensional protein identification technology. Reproducibility of the results was addressed by analysing and comparing five datasets using different protein identification tools available within the Sequest software. Furthermore, a comparison of three major releases of the Ensembl human protein database was performed to examine the effect of database updates on our results. We report here the benefit of repeated analysis of aliquots of the same fraction: first to increase the confidence in peptide identification by repeated confirmation in several aliquots; and second to assess experimental reproducibility. We demonstrate furthermore the effect of database modifications on the results and the importance of constantly re-analysing data with new releases to keep them consistent and up to date with the latest protein identities and predictions available.

Amino Acid Sequence↗
PubMed2001

A quantitative histochemistry technique for measuring regional distribution of acetylcholinesterase in the brain using digital scanning densitometry.

Studies of brain acetylcholinesterase (AChE) are traditionally based on biochemical assays, immunoreactivity, and histochemistry. Conventional histochemistry yields rich morphological data from tissue sections but yields quantitative results only with great difficulty. Several histochemical methods developed in recent years, including microdensitometry, microphotometry, and video-based histochemistry, are effective in quantitative and detailed study of AChE in tissue sections. However, they are usually time-consuming. As we report here, we adapted digital scanning densitometry to quantitate AChE histochemical staining in brain sections. The AChE and butyrylcholinesterase (BuChE), as measured by the method, were heterogeneously distributed throughout the brain, results that are consistent with those obtained by biochemical methods. The staining intensity is dependent on section thickness, substrate concentration, and reaction time. The cholinesterase inhibitor methyl paraoxon significantly decreased AChE staining intensity. Furthermore, data acquired from densitometry are similar to those obtained by video-based microscopy or by spectrophotometry. The advantage of the densitometric measurements compared to other quantitative histochemical methods is that it is very rapid while collecting data that are equivalent in quality. Because the digital scanning densitometers provide high quality and sensitive imaging, wide dynamic ranges, and convenient image analysis software, they are very useful tools in quantitative histochemistry.

Acetylcholinesterase↗
PubMed2000

[Effect of positioning errors on magnification factors in the mandible in digital panorama imaging].

Magnification factors (VF) in relation to various head positions were evaluated for a digital panoramic radiography machine (Orthophos DS, Sirona) by means of a dry skull phantom. Six metallic objects were attached to the facial layer of the mandible. A set of 170 digital radiographs (program 1) was produced, with defined positioning errors within the vertical and horizontal plane. Repeated digital measurements of the object images were performed by one reader, applying the mouse-driven measurement tool integrated in the proprietary software. In addition, the central layer of the radiographic device was experimentally determined and its location compared to that of the accurately positioned dry mandible. All objects were located on the outside of the central layer of minimum distortion and therefore placed towards the sensor. One- and two-way analysis of variance was applied for the statistical evaluation of the data, with VF as dependent variable and the positions as factors, respectively. Vertical inclinations of the skull affected horizontal VF only in the premolar region (p = 0.0069). However, when the skull was rotated within the horizontal plane, VF was significantly influenced in all anatomical regions of the mandible (p = 0.0001). This was particularly obvious in the premolar region, with a maximum variation of 10.3%. Fluctuations of VF were more pronounced in the premolar region than at the mandibular angle. We conclude from this study that, as expected, digital panoramic radiographs exhibit identical distortion effects as compared to conventional panoramic x-rays. Exact quantification of regional magnification requires (spherical) reference objects with known dimensions. Horizontal magnification is quite unreliable and far less reproducible than vertical magnification. Whenever several panoramic radiographs of one patient are to be compared quantitatively, accurate positioning of the patients' head is a necessary prerequisite.

Artifacts↗
PubMed2006

In vitro experiments and numerical simulations of airflow in realistic nasal airway geometry.

Pressure-flow relationships measured in human plastinated specimen of both nasal cavities and maxillary sinuses were compared to those obtained by numerical airflow simulations in a numerical three-dimensional reconstruction issued from CT scans of the plastinated specimen. For experiments, flow rates up to 1,500 ml/s were tested using three different gases: HeO(2), Air, and SF(6). Numerical inspiratory airflow simulations were performed for flow rates up to 353 ml/s in both the nostrils using a finite-volume-based method under steady-state conditions with CFD software using a laminar model. The good agreement between measured and numerically computed total pressure drops observed up to a flow rate of 250 ml/s is an important step to validate the ability of CFD software to describe flow in a physiologically realistic binasal model. The major total pressure drop was localized in the nasal valve region. Airflow was found to be predominant in the inferior median part of nasal cavities. Two main vortices were observed downstream from the nasal valve and toward the olfactory region. In the future, CFD software will be a useful tool for the clinician by providing a better understanding of the complexity of three-dimensional breathing flow in the nasal cavities allowing more appropriate management of the patient's symptoms.

Computer Simulation↗
PubMed2006

Electron tomography of ER, Golgi and related membrane systems.

A primary goal of cell biology is to uncover the mechanisms of cellular processes. A detailed structural understanding of the organelles and subcellular structures involved in these processes has often formed the foundation for the elucidation of their function. Electron tomography is a powerful technique for characterizing subcellular architecture and structural details in three dimensions. Electron tomography of cryofixed, freeze-substituted, and plastic-embedded samples allows three-dimensional visualization and display of dynamic, pleiomorphic structures at a resolution of approximately 7 nm in cell volumes up to approximately 25 microm(3). In this review, we describe the electron tomography protocols that we have employed to determine the 3D architecture of complex cellular structures, thereby gaining insights into their functional organization. We stress the need for studying specimens preserved by cryofixation methods to obtain accurate information on the geometry and size of cellular structures. We also discuss some of the challenges associated with the staining of certain types of membranes. Finally, we provide examples of how tomographic data can be analyzed, dissected, and displayed using the tools built into the IMOD software package.

Cell Membrane Structures↗
PubMed2005

Calculating virtual log P in the alkane/water system (log P(N)(alk)) and its derived parameters deltalog P(N)(oct-alk) and log D(pH)(alk).

Growing interest in the use of both the logarithm of the partition coefficient of the neutral species in the alkane/water system (log P(N)(alk)) and the difference between log P(N)(oct) (the logarithm of the partition coefficient of the neutral species in the n-octanol/water system) and log P(N)(alk) (Deltalog P(N)(oct-alk)) in the early stages of drug design has stimulated development of a computational tool based on the Volsurf software to predict virtual (=of each conformer) log P(N)(alk) and virtual log P(N)(oct). From these two pieces of data, it is then possible to calculate Deltalog P(N)(oct-alk) for a given compound as the difference between log P(N)(oct) and log P(N)(alk). Once the pK(a) is known and the legitimacy of neglecting the contribution made by the ionized species has been checked, it is also possible to calculate log D(pH)(alk), which might be an important lipophilicity descriptor in absorption, distribution, metabolism, and excretion (ADME) prediction, from log P(N)(alk).

1-Octanol↗
PubMed2025

Bioinformatic analyses and validated experiments reveal an aging hallmark gene set and protective miR of coronary artery disease.

To investigate how aging hallmarks exert roles in the age-related disease of coronary artery disease (CAD). R software and the GEO2R online tool identified differentially expressed genes (DEGs) and differentially expressed microRNAs (DEMis) in CAD microarray datasets from the Gene Expression Omnibus. Genes common to target genes of DEMis, DEGs, and an aging gene list from Human Aging Genomic Resources were then identified and analyzed for protein-protein interactions and functional and pathway enrichment. An miR-mRNA network was constructed using Cytoscape. Receiver operating characteristic curve analysis assessed the diagnostic utility of DEMis in CAD. The expression of two DEMis from a CAD cohort was employed to validate the findings. An aging hallmark gene set, comprising 18 genes, was delineated, with the hub gene TP53 established through protein-protein interaction and microRNA-mRNA networks. Within the microRNA-mRNA network, two DEMis (hsa-miR-423-5p and hsa-miR-564) potentially regulated TP53, rendering them potential CAD biomarkers, as indicated by their area under the curves (AUC) surpassing 0.6. Validation experiments corroborated an AUC of 0.7002 for hsa-miR-423-5p and 0.7261 for hsa-miR-564, highlighting its protective association with CAD. Combining hsa-miR-423-5p, hsa-miR-564, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), white blood cells (WBC) achieved an area under the receiver operating characteristics curve of 0.783. A CAD-associated gene set was identified, with TP53 as the central hub. Hsa-miR-564 emerged as a potential protective factor against CAD.

Humans↗
PubMed2006

In-vivo measurement of brain relaxation after lobectomies.

Very little data exists on the visco-elastic properties of the living human brain tissue and collection of such data is vital for mechanical modelling. The purpose of this study was to measure the rate of relaxation of brain that has been compressed by tumour after surgical decompression. Seven patients who underwent a lobectomy for an intracranial space occupying lesion were included in the study. All underwent two CT scans within the first 24 h after the surgery. Volumes of the residual void on the serial CT scan were calculated using tools in the image acquisition software. There was a rapid expansion of the brain to fill up the void space in the first 24 h after surgery. The average rate of relaxation of the compressed brain is 2.25(0.76 - 6.64) ml/h. The graphs plotted for the volume of the void space against the time after surgery when the CT scans were done can be used to further explore the dynamics of brain relaxation. The rate of brain relaxation in the first 24 h after removal of a mass lesion averages 2.25(0.76 - 6.64) ml/h in this study. Further studies using more frequent data collection would allow for more accurate definition of the rate of relaxation.

Aged↗
PubMed2004

Methods for the differential integrative omic analysis of plasma from a transgenic disease animal model.

Multitiered quantitative analysis of biological systems is rapidly becoming the desired approach to study hierarchical functional interactions between proteins and metabolites. We describe here a novel systematic approach to analyze organisms with complex metabolic regulatory networks. By using precise analytical methods to measure biochemical constituents and their relative abundance in whole plasma of transgenic ApoE*3-Leiden mice and an isogenic wild-type control group, simultaneous snapshots of metabolic and protein states were obtained. Novel data processing and multivariate analysis tools such as Impurity Resolution Software (IMPRESS) and Windows-based linear fit program (WINLIN) were used to compare protein and metabolic profiles in parallel. Canonical correlations of the resulting data show quantitative relationships between heterogeneous components in the TG animals. These results, obtained solely from whole plasma analysis allowed us, in a rapid manner, to corroborate previous findings as well as find new events pertaining to dominant and peripheral events in lipoprotein metabolism of a genetically modified mammalian organism in relation to ApoE3, a key mediator of lipoprotein metabolism.

Animals↗
PubMed2004

BagBoosting for tumor classification with gene expression data.

MOTIVATION: Microarray experiments are expected to contribute significantly to the progress in cancer treatment by enabling a precise and early diagnosis. They create a need for class prediction tools, which can deal with a large number of highly correlated input variables, perform feature selection and provide class probability estimates that serve as a quantification of the predictive uncertainty. A very promising solution is to combine the two ensemble schemes bagging and boosting to a novel algorithm called BagBoosting. RESULTS: When bagging is used as a module in boosting, the resulting classifier consistently improves the predictive performance and the probability estimates of both bagging and boosting on real and simulated gene expression data. This quasi-guaranteed improvement can be obtained by simply making a bigger computing effort. The advantageous predictive potential is also confirmed by comparing BagBoosting to several established class prediction tools for microarray data. AVAILABILITY: Software for the modified boosting algorithms, for benchmark studies and for the simulation of microarray data are available as an R package under GNU public license at http://stat.ethz.ch/~dettling/bagboost.html.

Algorithms↗
PubMed1999

Training for quality management: report on a nationwide distance learning initiative for physicians in Spain.

Under the sponsorship of a pharmaceutical firm, a distance-learning course on Quality Management methods was developed at the University of Murcia (Spain) and offered nationwide to primary health care physicians working in the public system. A total of 7104 physicians (47.7% of the census) signed up (at least one in 92.2% of the health centres). The course content follows the author's model of quality improvement, monitoring and design trilogy, but focuses mainly on methods for a quality improvement cycle using a learning-by-doing and problem-solving approach. The unexpected success of this initiative has led us to reflect on the interest in learning about quality improvement methods shown by physicians, the usefulness of the distance-learning approach, and also to continue the project with new initiatives such as: a summary poster, software containing all the necessary tools and data analysis for quality improvement, and a manual.

Curriculum↗
PubMed2001

A phantom study of the geometric accuracy of computed tomographic and magnetic resonance imaging stereotactic localization with the Leksell stereotactic system.

OBJECTIVE: To assess the spatial accuracy of magnetic resonance imaging (MRI) and computed tomographic stereotactic localization with the Leksell stereotactic system. METHODS: The phantom was constructed in the shape of a box, 164 mm in each dimension, with three perpendicular arrays of solid acrylic rod, 5 mm in diameter and spaced 30 mm apart within the phantom. In this study, images from two different MRI scanners and a computed tomographic scanner were obtained using the same Leksell (Elekta Instruments, Stockholm, Sweden) head frame placement. The coordinates of the rod images in the three principal planes were measured by using a tool provided with Leksell GammaPlan software (Elekta Instruments, Norcross, GA) and were compared with the physical phantom measurements. RESULTS: The greatest distortion was found around the periphery, and the least distortion (<1.5 mm) was present in the middle and most other areas of the phantom. In the phantom study using computed tomography, the mean values of the maximum errors for the x, y, and z axes were 1.0 mm (range, 0.2-1.3 mm), 0.4 mm (range, 0.1-0.8 mm), and 3.8 mm (range, 1.9-5.1 mm), respectively. The mean values of the maximum errors when using the Philips MRI scanner (Philips Medical Systems, Shelton, CT) were 0.9 mm (range, 0.4-1.7 mm), 0.2 mm (range, 0.0-0.7 mm), and 1.9 mm (range, 1.3-2.3 mm), respectively. Using the Siemens MRI scanner (Siemens Medical Systems, New York, NY), these values were 0.4 mm (range, 0.0-0.7 mm), 0.6 mm (range, 0.0-1.0 mm), and 1.6 mm (range, 0.8-2.0 mm), respectively. The geometric accuracy of the MRI scans when using the Siemens scanner was greatly improved after the implementation of a new software patch provided by the manufacturer. The accuracy also varied with the direction of phase encoding. CONCLUSION: The accuracy of target localization for most intracranial lesions during stereotactic radiosurgery can be achieved within the size of a voxel, especially by using the Siemens MRI scanner at current specifications and with a new software patch. However, caution is warranted when imaging peripheral lesions, where the distortion is greatest.

Humans↗
PubMedDate not supplied

Design and development of an artificial implantable lung using multiobjective genetic algorithm: evaluation of gas exchange performance.

In this study, we constructed an automatic optimization system applying the multiobjective genetic algorithm (MOGA) and developed an artificial implantable lung possessing antithrombogenicity and high gas exchange performance based upon fluid dynamics. This system consists of a three dimenstional CAD system, computational fluid dynamics software, and the multiobjective optimization tool modeFRONTIER (ESTECO CO., Trieste, Italy). The objectives were to minimize the volume of the region having a flow rate of less than 0.5 mm/s by assuming that thrombus formation occurs at this limit (ObjTF) and to minimize the standard deviation of the flow rate in the hollow fiber to obtain high gas exchange performance (ObjGEP). In optimization 1, the arc heights (six variables) and the distance between cross-sections (two variables) were used as design variables in the inflow and outflow portions. In optimization 2, the edges (two variables) of the inflow and outflow portions were optimized in the resulting designs from optimization 1. The optimum designs were manufactured using the rapid prototyping system and were examined by evaluating gas exchange performance (ObjGEP) in vitro. Gas exchange performance increased as the improvement ratio of ObjGEP became higher. For the optimum design (improvement ratio of 74.8% for ObjGEP), O2 transfer increased by an average of 18.4%, and CO2 transfer increased by an average of 40.5% when compared with the original design. The results suggest that this system was not only effective for reducing the time, cost, and labor of developing artificial organs but was also useful as a design and development support system for high performance artificial organs for transplantation.

Algorithms↗
PubMed2005

The influence of environmental adaptation on bacterial genome structure.

AIMS: Researchers have long been puzzled by the diversity of life. Now that the complete genomic sequence of many organisms has been determined, it is possible to evaluate the impact of organismal variation on sequence structure or vice versa. The aim of this investigation was to explore genomic changes mandated by organismal adaptation to its ecological niches. METHODS AND RESULTS: Coding sequences from three phylogenetically related bacterial species namely Mycoplasma genitalium, M. pneumoniae and Ureaplasma urealyticum were subject to in depth sequence analyses. M. genitalium and M. pneumoniae both belong to the genus Mycoplasma while U. urealyticum is a member of the genus Ureaplasma. However, M. genitalium and U. urealyticum are urogenital pathogens while M. pneumoniae is a respiratory pathogen. Complete transcriptomes were downloaded from NCBI for each species, and were subject to in silico investigation using in-house software, and public sequence analysis tools. Clear similarities in transcriptome structure were identified among the functionally similar species M. genitalium and U. urealyticum while no such relationship was identified among the phylogenetically related species M. genitalium and M. pneumoniae. CONCLUSIONS: It is plausible to conclude that, in these bacterial species, environmental stimuli might be more influential in shaping sequence signatures than phylogenetic relationships. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that molecular signatures within the transcriptomes of the species examined are likely to be a product of evolutionary adaptation to diverse environmental ecological stimuli, and not a result of common phylogeny.

Adaptation, Biological↗