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PubMed1994

Computer program for connection and data management of an automated coagulation system: the KC 10.

In Europe, the KC 10, manufactured by Amelung Germany, is one of the instruments most commonly found in coagulation laboratories. For facilitating the work of technical validation, we wrote a software adapted to any IBM or compatible PC running under MS-DOS, to manage the analyser performance. Data are automatically collected via the BCD interface from the analyser or keyed in for the other techniques. The software deals with 64 different analyses entirely 'user defined'. An 'electronic worksheet' presents the results, by page of ten patients. This enables the laboratory technician to assess the coherence of the various data and to perform verifications or complementary tests if necessary. As an option, a blinking asterisk can signal all results outside predetermined range. By moving the cursor through the table, a test result can be deleted, modified or added. A function displays the patient's previous files in a window because the data are recorded in long-term archives at the end of the day. This long-term recording allows a search of previous files to decide additional tests if the patient is unknown. A daily archive function classifies and prints the whole day's work in alphabetical order. A protocol of communication allows connection to a mainframe Bayer-Technicon computer. This program and the user's manual are free, available on request from address above.

Blood Coagulation Tests↗
PubMed2004

A sequencing-based typing method for HLA-DQA1 alleles.

Sequencing-based typing (SBT) is the most comprehensive method for characterizing human leukocyte antigen gene polymorphisms. Development of a SBT method for DQA1 is hampered because of a deletion of codon 56 in nearly half of the known DQA1 alleles. Sequence electropherograms of heterozygous samples comprising a deletion allele and a non-deletion allele display misalignment after codon 56 because of a three base-pair shift in the deletion allele. To overcome this problem, we have designed three group-specific primer sets to selectively amplify the deletion alleles from the nondeletion alleles. DNA samples are initially polymerase chain reaction (PCR)-typed using these primer sets along with an internal positive control primer set specific to growth hormone gene 1 (hGH1). The positive group-specific PCR reactions were selectively repeated without hGH1 control primers, and the amplicons were used as template in sequencing reactions. The sequence data were analyzed to obtain DQA1 types using ABI MatchTools software as well as the newly available Conexio Genomics Assign SBT Genotyping Software. The method was validated using a panel of reference DNA from the University of California, Los Angeles, International DNA Exchange Program. We conclude that the present SBT method is a technically simple and robust procedure to characterize the sequence polymorphisms in exon 2 of DQA1 gene.

Alleles↗
PubMed2006

Toxicogenomics of endoplasmic reticulum stress inducer tunicamycin in the small intestine and liver of Nrf2 knockout and C57BL/6J mice.

This objective of this study was to investigate the toxicogenomics and the spatial regulation of global gene expression profiles elicited by endoplasmic reticulum (ER) stress inducer tunicamycin (TM) in mouse small intestine and liver as well as to identify TM-modulated nuclear factor-E2-related factor 2 (Nrf2)-dependent genes. Gene expression profiles were analyzed using 45,000 Affymetrix mouse genome 430 2.0 array and GeneSpring 7.2 software. Microarray results were validated by quantitative real-time reverse transcription-PCR analyses. Clusters of genes that were either induced or suppressed more than two-fold by TM treatment compared with vehicle in C57BL/6J/Nrf2 (-/-; knockout) and C57BL/6J Nrf2 (+/+; wildtype) mice genotypes were identified. Amongst these, in small intestine and liver, 1291 and 750 genes, respectively, were identified as Nrf2-dependent and upregulated, and 1370 and 943 genes, respectively, as Nrf2-dependent and downregulated. Based on their biological functions, these genes can be categorized into molecular chaperones and heat shock proteins, ubiquitination/proteolysis, apoptosis/cell cycle, electron transport, detoxification, cell growth/differentiation, signaling molecules/interacting partners, kinases and phosphatases, transport, biosynthesis/metabolism, nuclear assembly and processing, and genes related to calcium and glucose homeostasis. Phase II detoxification/antioxidant genes as well as putative interacting partners of Nrf2 such as nuclear corepressors and coactivators, were also identified as Nrf2-dependent genes. The identification of TM-regulated and Nrf2-dependent genes in the unfolded protein response to ER stress not only provides potential novel insights into the gestalt biological effects of TM on the toxicogenomics and spatial regulation of global gene expression profiles in cancer pharmacology and toxicology, but also points to the pivotal role of Nrf2 in these biological processes.

Animals↗
PubMed2002

[Antibiotic resistance in blood isolates of Staphylococcus aureus in 31 Spanish hospitals participating in the European Antimicrobial Resistance Surveillance System (2000)].

BACKGROUND: In 1998, the European Union funded the European Antimicrobial Resistance Surveillance System. We present here Staphylococcus aureus data in 2000 in Spain. MATERIAL AND METHOD: 31 hospitals were involved, covering almost 25% Spanish total population. All nosocomial blood isolates of S. aureus were included. Each laboratory carried out microbiological studies with its own usual methods. Quality control was carried out by UK National External Quality (NEQAS). A questionnaire including hospital, patient and specimen data was filled out for each isolate. Results were registered in a single database and analyzed and validated with Whonet. 5 software. RESULTS: Invasive S. aureus was isolated in 903 patients. Overall incidence was 1.45/1000 admitted patients. Resistance was 28.1% (95% CI, 25.2-31.1) to oxacillin (O), 26.6% to ciprofloxacin (C), 23.8% to erythromycin (E) and 16.6% to gentamicin (G). Multiresistance was noticed in 80% oxacillin-resistant strains. More frequent multiresistance profiles were OECG (11.3% of all isolates) and OEC (6.3%). Oxacillin resistance was higher in ICU units (44.5%) than in other medical departments (27.4%) (p < 0.001). Hospitals with 500 beds or more showed 36.4% prevalence of O resistance, while in hospitals having less than 500 beds it was 18.8% (p < 0.001). A decreased susceptibility to vancomycin was not detected. CONCLUSIONS: In Spain, invasive S. aureus shows a high prevalence of resistance to oxacillin, ciprofloxacin, erythromycin and gentamicin. Most oxacillin-resistant strains were resistant to three or more antibiotics. Nearly 50% oxacillin-resistant isolates were susceptible to gentamicin. Oxacillin resistance and resistance to multiple antibiotics was more frequent in ICU units and in hospitals with 500 beds or more.

Adolescent↗
PubMed2005

An integrated platform for automated analysis of protein NMR structures.

Recent developments provide automated analysis of NMR assignments and three-dimensional (3D) structures of proteins. These approaches are generally applicable to proteins ranging from about 50 to 150 amino acids. In this chapter, we summarize progress by the Northeast Structural Genomics Consortium in standardizing the NMR data collection process for protein structure determination and in building an integrated platform for automated protein NMR structure analysis. Our integrated platform includes the following principal steps: (1) standardized NMR data collection, (2) standardized data processing (including spectral referencing and Fourier transformation), (3) automated peak picking and peak list editing, (4) automated analysis of resonance assignments, (5) automated analysis of NOESY data together with 3D structure determination, and (6) methods for protein structure validation. In particular, the software AutoStructure for automated NOESY data analysis is described in this chapter, together with a discussion of practical considerations for its use in high-throughput structure production efforts. The critical area of data quality assessment has evolved significantly over the past few years and involves evaluation of both intermediate and final peak lists, resonance assignments, and structural information derived from the NMR data. Methods for quality control of each of the major automated analysis steps in our platform are also discussed. Despite significant remaining challenges, when good quality data are available, automated analysis of protein NMR assignments and structures with this platform is both fast and reliable.

Data Interpretation, Statistical↗
PubMed2000

Hippocampal and cerebellar volumetry in serially acquired MRI volume scans.

In this work, we describe methodologies for serial volumetric measurements of hippocampi and cerebella. Serial scans were co-registered and intensity matched prior to the volumetric measurements. Manual drawing was used to define the boundaries of the hippocampi. For the cerebellar volumetric measurements, the brain was automatically segmented from the co-registered scans; manual drawing was used to define the boundary between the cerebellum and the cerebrum and brainstem. The operator was blinded to the nature of the subject (patient or normal control) and the chronological order of the scans. The coefficient of reliability of hippocampal volume measurements in a group of 20 controls was 0.078 cm(3) (3.1% of the mean baseline volume); for the cerebellum, the value was 3.8 cm(3) (3.0% of the mean baseline volume). We conclude that the methods presented are valid and that the software provides a useful integrated tool for the quantitative analysis of structural changes in serially acquired volume MRI data in prospective, blinded studies.

Adult↗
PubMed2002

Exaggeration of nonculprit stenosis severity during acute myocardial infarction: implications for immediate multivessel revascularization.

OBJECTIVES: This study was designed to assess the prevalence and clinical significance of exaggerated nonculprit lesion stenosis in the setting of acute (<12 h) myocardial infarction (AMI). BACKGROUND: Although microvascular spasm may reduce nonculprit artery flow during AMI, it is unknown whether increased tone may exaggerate nonculprit lesion severity. METHODS: In patients with additional angiography within nine months of AMI, and significant nonculprit lesions imaged in matching views, stenosis severity was compared between studies in a random blinded fashion using validated quantitative coronary angiography software. Baseline demographics, medications, hemodynamics at each study, and clinical status at follow-up (infarct/unstable angina/stable angina) were used to determine the independent influence of the infarct presentation on stenosis exaggeration. RESULTS: From 548 patients with AMI (1/99 to 6/01, 321 with multivessel disease), 112 had additional angiography; of these 48 had 59 lesions suitable for analysis. Between infarct and noninfarct angiograms there was a significant change in minimal lumen diameter (1.53 +/- 0.51 mm vs. 1.78 +/- 0.65 mm, p < 0.001) and percentage stenosis (49.3 +/- 14.5% vs. 40.4 +/- 16.6%, p < 0.0001) of the nonculprit lesion without significant change in reference segment diameter, which was not predicted by changes in medication or hemodynamics. Twenty-one percent of patients had lesions >50% at AMI that were <50% at non-AMI angiography. Infarct versus noninfarct setting was the only significant independent predictor of change in nonculprit stenosis. CONCLUSIONS: Significant exaggeration of nonculprit lesion stenosis severity occurs at infarct angiography, which may affect revascularization decision making in an appreciable number of patients.

Aged↗
PubMed2002

QRST subtraction combined with a pacemap catalogue for the prediction of ectopy source by surface electrocardiogram in patients with paroxysmal atrial fibrillation.

OBJECTIVES: This study evaluated the use of ectopic P-wave morphology to localize pulmonary vein (PV) and non-PV sources of atrial ectopics in patients with paroxysmal atrial fibrillation (PAF). BACKGROUND: The vectorial information embodied in the morphology of ectopic P waves is concealed by overlying T waves. METHODS: The P-wave morphology of 56 ectopics was prospectively analyzed in 44 patients with PAF (age, 52 +/- 12 years; 36 male) by subtracting the adjacent QRST from the QRST-ectopic P-wave complex using custom-designed software. Subtraction fidelity was validated in 15 other patients (55 +/- 19 years, 11 male) by comparing drive beats with simulated ectopics (S2 from the same site) unmasked by subtracting overlying QRST. An algorithm combined with PV pacemaps was used to predict PV sources. Subtracted ectopic P-wave morphologies after PV disconnection were compared with PV and non-PV site pacemaps. Localization was confirmed by mapping and successful ablation. RESULTS: A > or =10-lead electrocardiogram (ECG) match was observed in 92% of 644 simulated ectopics (coupling intervals: 190 to 520 ms). In PAF patients, 37 spontaneous ectopics originated from the PV, while 19 were noted after PV disconnection. Using the P-wave algorithm alone, correct prediction of PV origin was achieved in 30/37 ectopics (81%). Combination with PV pacemaps allowed correct prediction in 34/37 (92%). After PV disconnection, ECG localization predicted successful ablation sites in 16/19 (84%). CONCLUSIONS: Comparison of subtracted ectopic P waves with a pacemap catalogue provides a simple and accurate 12-lead ECG-based method for localization, which can facilitate ablation of arrhythmia triggers irrespective of origin from the PV or elsewhere.

Adult↗
PubMed1999

Postgraduate journal club as a means of promoting evidence-based obstetrics and gynaecology.

We assessed the feasibility of a new educational programme to teach critical appraisal of the medical literature to postgraduate trainees. The new programme used a journal club format where selection of topics and articles was driven by clinical problems arising in day-to-day practice. Papers were appraised critically according to validated guidelines using computer software for appraisal, electronic storage and retrieval. Over the initial 4-month period the journal club produced 17 critically appraised topics, two of which were published in peer-reviewed journals. During the study, trainees' reading time improved from a median of 2.0 hours (range 1-5 hours) to 3.5 hours (range 2-8 hours) (P = 0.026) and their knowledge scores improved from a mean of 50.8 (SD 4.0) to 62.9 (SD 4.3) (P = 0.003). We conclude that a journal club supported by electronic means of critical appraisal and dissemination of appraised information can be used to encourage the practice of evidence-based medicine.

Journal Article↗
PubMed2006

K-edge digital subtraction imaging with dichromatic x-ray sources: SNR and dose studies.

The aim of the present work is to analytically evaluate the signal to noise ratio (SNR) and the delivered dose in K-edge digital subtraction imaging (KES) using two types of x-ray sources: a monochromatic x-ray source (available at synchrotron radiation facilities and considered as gold standard) and a quasi-monochromatic compact source. The energy separation DeltaE between the two monochromatic beams is 1 keV and 4 keV for the two sources, respectively. The evaluation has been performed for both radiography and computed tomography. Different geometries have been studied to mimic clinical situations. In mammography, a pathology perfused by a contrast agent has been modelled; in angiography, a vessel superimposed to a ventricle or a stand-alone artery stenosis has been studied. The SNR and the skin dose have been calculated as a function of the detail diameter, the contrast agent (iodine and gadolinium), and its concentration in the tissues. Results show that for DeltaE = 4 keV a slightly higher delivered dose is required to obtain the same SNR with respect to DeltaE < 1 keV. A similar study has been performed for KES-CT. Computer simulations of CT images performed with Snark software are shown to validate the analytical calculations.

Algorithms↗
PubMed2004

Enumerative and binomial sequential sampling plans for soybean aphid (Homoptera: Aphididae) in soybean.

Since the discovery of the soybean aphid, Aphis glycines Matsumura, in midwestern U.S. soybean, Glycine max L., in 2000, the aphid has become a significant economic pest. Basic information about estimating population density within fields is unknown. Therefore, we developed two sampling plans to efficiently characterize A. glycines densities. Enumerative and binomial sequential plans were developed using 89 data sets collected from 10 commercial fields sampled during 2001-2003. Re-sampling software was used to validate the enumerative plan on whole plant counts, based on Taylor's power law parameters (a = 9.157 and b = 1.543). For research applications, the enumerative plan was modified to provide an actual precision level of 0.10 (SE/mean), which resulted in an average sample number of 310 individual plants. For integrated pest management (IPM) purposes, we developed an enumerative plan with an actual precision of 0.25, which resulted in an average sample number of 38 individual plants. For IPM applications, the binomial plan will likely be more practical. Binomial plans were developed using two tally thresholds at five action thresholds. Final analysis of the operating characteristic curve for each plan indicated that the tally threshold of > or = 40 aphids per plant, and an action threshold of 0.837 (84% of the plants infested) provided the most correct treat (4%) and no-treat (95%) decisions, with very low incorrect treat (0.5%) and no-treat (0.5%) decisions. A tally threshold of > or = 40 aphids per plant and action thresholds of 84% of plants infested is equivalent to a mean density of 250 aphids per plant, a recently recommended economic threshold. Using this threshold, the minimum required sample number for the binomial plan was 11 plants.

Agriculture↗
PubMed2002

Computerized content analysis of some adolescent writings of Napoleon Bonaparte: a test of the validity of the method.

The aim of this study was to test the validity of a computer software program previously demonstrated to be capable of making DSM-IV neuropsychiatric diagnoses from the content analysis of speech or verbal texts. In this report, the computer program was applied to three personal writings of Napoleon Bonaparte when he was 12 to 16 years of age. The accuracy of the neuropsychiatric evaluations derived from the computerized content analysis of these writings of Napoleon was independently corroborated by two biographers who have described pertinent details concerning his life situations, moods, and other emotional reactions during this adolescent period of his life. The relevance of this type of computer technology to psychohistorical research and clinical psychiatry is suggested.

Diagnosis, Computer-Assisted↗
PubMed2005

Intervertebral motion after incremental damage to the posterior structures of the cervical spine.

STUDY DESIGN: Compare intervertebral motion after incremental damage to posterior cervical structures in whole cadavers to motion in asymptomatic subjects. OBJECTIVE: Determine if damage to the posterior structures of the cervical spine can be detected by quantitative analysis of flexion-extension radiographs. SUMMARY OF BACKGROUND DATA: Simulated damage to the posterior structures of the cervical spine can change intervertebral motion, if intervertebral motion before damage is known. It is not known if intervertebral motion measured from flexion-extension radiographs can be used to detect damage to the posterior structures if motion before damage is not known. METHODS: Incremental injury to posterior ligaments and facet joints was simulated in 12 whole cadavers. Intervertebral motion was measured from flexion-extension images using validated and clinically applicable software. Measurements were compared to previously published measurements for asymptomatic subjects. RESULTS: Extensive damage could be simulated in all the cervical spines without intervertebral motion exceeding the 95% confidence limits for asymptomatic subjects. After sectioning all posterior ligaments, destroying both facet joints, and then sectioning the posterior longitudinal ligaments, intervertebral motion exceeded the 95% confidence intervals in 69% of the cadavers. Intervertebral shear decreased with incremental damage to posterior structures. CONCLUSIONS: Radiographic assessment of the cervical spine may not be sufficient to exclude even extensive damage to the posterior structures of the cervical spine.

Arthrography↗
PubMed2000

Compartmental modeling of postprandial dietary nitrogen distribution in humans.

A linear 11-compartment model was developed to describe and simulate the postprandial distribution of dietary nitrogen. The values of its 15 constant diffusion coefficients were estimated from the experimental measurement of (15)N nitrogen kinetics in the intestine, blood, and urine after the oral administration of (15)N-labeled milk protein in humans. Model structure development, parameter estimation, and sensibility analysis were achieved using SAAM II and SIMUSOLV softwares. The model was validated at each stage of its development by testing successively its a priori and a posteriori identifiability. The model predicted that, 8 h after a meal, the dietary nitrogen retained in the body comprised 28% free amino acids and 72% protein, approximately 30% being recovered in the splanchnic bed vs. 70% in the peripheral area. Twelve hours after the meal, these values had decreased to 18 and 23% for the free amino acid fraction and splanchnic nitrogen, respectively. Such a model constitutes a useful, explanatory tool to describe the processes involved in the metabolic utilization of dietary proteins.

Diet↗
PubMed2006

Ingenuity network-assisted transcription profiling: Identification of a new pharmacologic mechanism for MK886.

The small molecular inhibitor MK886 is known to block 5-lipoxygenase-activating protein ALOX5AP and shows antitumor activity in multiple human cell lines. The broad antitumor therapeutic window reported in vivo for MK886 in rodents supports further consideration of this structural class. Better understanding of the mode of action of the drug is important for application in humans to take place. Affymetrix microarray study was conducted to explore MK886 pharmacologic mechanism. Ingenuity Pathway Analysis software was applied to validate the results at the transcriptional level by putting them in the context of an experimental proteomic network. Genes most affected by MK886 included actin B and focal adhesion components. A subsequent National Cancer Institute-60 panel study, RT-PCR validation followed by confocal microscopy, and Western blotting also pointed to actin B down-regulation, filamentous actin loss, and disorganization of the transcription machinery. In agreement with these observations, MK886 was found to enhance the effect of UV radiation in H720 lung cancer cell line. In light of the modification of cytoskeleton and cell motility by lipid phosphoinositide 3-kinase products, MK886 interaction with actin B might be biologically important. The low toxicity of MK886 in vivo was modeled and explained by binding and transport by dietary lipids. The rate of lipid absorbance is generally higher for tumors, suggesting a promise of a targeted liposome-based delivery system for this drug. These results suggest a novel antitumor pharmacologic mechanism.

Actins↗
PubMed1995

Standard operating procedure for the registration and computer-supported evaluation of pharmaco-EEG data. 'EEG in Phase I' of the Collegium Internationale Psychiatriae Scalarum (CIPS).

The working team 'EEG in Phase I' of the Collegium Internationale Psychiatriae Scalarum presents a standard operating procedure (SOP) for the registration and computer-supported evaluation of pharmaco-EEG data, which is based on published guidelines. The minimum standard for recording, amplifying and filtering, validation of hardware and software, artifact treatment and fast Fourier analysis is described in a tabulated from and further explained as accompanying comments. The available SOP can be the basis for the working out of laboratory-specific SOPs. Compliance with the SOP guarantees the possibility of citation by the International Pharmaco-EEG Group (IPEG), Association for Methodology and Documentation in Psychiatry (AMDP), and Collegium Internationale Psychiatriae Scalarum (CIPS). Furthermore, an optimal standard is recommended where appropriate, which functions as a guideline.

Electroencephalography↗
PubMed2006

Analysis of the Saccharomyces cerevisiae proteome with PeptideAtlas.

We present the Saccharomyces cerevisiae PeptideAtlas composed from 47 diverse experiments and 4.9 million tandem mass spectra. The observed peptides align to 61% of Saccharomyces Genome Database (SGD) open reading frames (ORFs), 49% of the uncharacterized SGD ORFs, 54% of S. cerevisiae ORFs with a Gene Ontology annotation of 'molecular function unknown', and 76% of ORFs with Gene names. We highlight the use of this resource for data mining, construction of high quality lists for targeted proteomics, validation of proteins, and software development.

Codon↗
PubMed2003

[Communication prostheses and behavioral alignment in hospital leaflets].

Review was made of publications that describe experience with printed material distributed to the lay public in hospital institutions. From the 146 leaflets examined, those aimed at professionals or disabled people, thus leaving 75 papers that illustrate the present pattern for the rationality behind the production, use and evaluation of this type of resource. In a general manner, such leaflets invest in the power of "ideal printed information" to align behavior with the hospital's biomedical agenda. The underlying rationality that permeates them perceives the "perfect information package" as one that efficiently describes its technical content for the purpose of unidirectional persuasion, is up-to-date in relation to readability scales and embellished by graphic design, and emphasizes the priorities defined by the professionals. Such "communication prostheses" should be capable of electronic validation by means of software suitable for proportioning the "doses" to the subject matter. Information as a drug, cognitivism, the lack of research on message reception and the need for communicative action for the deconstruction of systems of closed thinking within the hospital environment have been discussed.

Behavior↗