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Real-time display of flow-pressure-volume loops.

Graphic display of respiratory waveforms can be valuable for monitoring the progress of ventilated patients. A system has been developed that can display flow-pressure-volume loops as derived from a patient's respiratory circuit in real time. It can also display, store, print, and retrieve ventilatory waveforms. Five loops can be displayed at once: current, previous, reference, "ideal," and previously saved. Two components, the data-display device (DDD) and the data-collection device (DCD), comprise the system. An IBM 286/386 computer with a graphics card (VGA) and bidirectional parallel port is used for the DDD; an eight-bit microprocessor card and an A/D convertor card make up the DCD. A real-time multitasking operating system was written to control the DDD, while the DCD operates from in-line assembly code. The DCD samples the pressure and flow sensors at 100 Hz and looks for a complete flow waveform pattern based on flow slope. These waveforms are then passed to the DDD via the mutual parallel port. Within the DDD a process integrates the flow to create a volume signal and performs a multilinear regression on the pressure, flow, and volume data to calculate the elastance, resistance, pressure offset, and coefficient of determination. Elastance, resistance, and offset are used to calculate Pr and Pc where: Pr[k] = P[k]-offset-(elastance.V[k]) and Pc[k] = P[k]-offset-(resistance.F[k]). Volume vs. Pc and flow vs. Pr can be displayed in real time. Patient data from previous clinical tests were loaded into the device to verify the software calculations. An analog waveform generator was used to simulate flow and pressure waveforms that validated the system.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Graphics↗

Expansion thoracoplasty: the surgical technique of opening-wedge thoracostomy. Surgical technique.

BACKGROUND: Children with congenital thoracic scoliosis associated with fused ribs with a unilateral unsegmented bar adjacent to convex hemivertebrae will invariably have curve progression without treatment. Surgery has been thought to have a negligible growth-inhibition effect on the thoracic spine in such patients because it has been assumed that the concave side of the curve and the unilateral unsegmented bar do not grow, but we are unaware of any conclusive studies regarding this assumption. METHODS: The changes in the length of the concave and convex sides, anterior and posterior vertebral edges, posterior arch, and unilateral unsegmented bars of the thoracic spine were measured in the twenty-one children with congenital scoliosis and fused ribs after expansion thoracoplasty had been carried out with use of a vertical, expandable titanium prosthetic rib. Three of these children had undergone posterior spinal fusion previously. Measurements were made with use of a three-dimensional software program that analyzed baseline and follow-up computed tomography scans. The technique was validated through measurement of the thorax of a small female adult cadaver. RESULTS: The patients without spine fusion had an average age of 3.3 years at the time of the baseline computed tomography scan, and the average duration of follow-up was 4.2 years. On the average, these patients showed significant growth (p < 0.0001) of the concave side of the thoracic spine (an increase in length of 7.9 mm/yr, or 7.1%/yr) and the convex side (8.3 mm/yr, or 6.4%/yr) compared with the baseline lengths. There was no significant difference in the increases in length (p = 0.38) between the concave and convex sides. Eleven patients with an unsegmented bar had an average 7.3% increase in the length of the bar (p < 0.0001). In the three children with prior spinal fusion, the increase in length averaged only 4.6 mm/yr (3%/yr) on the concave side of the thoracic spine and 3.7 mm/yr (2.2%/yr) on the convex side; both increases were significant (p < 0.0001). CONCLUSIONS: Longitudinal growth of the thoracic spine in a normal child has been estimated to be 0.6 cm/yr between the ages of five and nine years. After expansion thoracoplasty, growth of the thoracic spine was approximately 8 mm/yr in our series of children with congenital scoliosis and fused ribs. After expansion thoracoplasty, both the concave and the convex side of the thoracic spine and unilateral unsegmented bars appeared to grow in these patients. When a thorax is already foreshortened by congenital scoliosis, control of spine deformity with expansion thoracoplasty allows growth of the thoracic spine, and it is likely that the longer thorax provides additional volume for growth of the underlying lungs with probable clinical benefit.

Child↗

[Identification of stage Ib specific related genes in lung squamous cell cancer by oligonucleotide array].

OBJECTIVE: To establish gene expression profile of stage Ib and IIIa primary lung squamous cell cancer (SCC) within whole genome and identify genes specifically expressed in stage Ib of SCC. METHODS: Total RNA was extracted from the normal, stage Ib and IIIa lung SCC tissue. cRNA probes prepared from total RNA were hybridized with pretreatment oligonucleotide chip containing 22215 genes. The resultant data were treated with MSV 5.0 software and looked up on the affymetrix website. RT-PCR examination were used to validated the results from chip analysis. RESULTS: Comparing with the normal lung, difference genes expressed in Ib SCC are totally 1764, among which 571 were upregulated and 1193 were downregulated, and in stage IIIa, they are 554, 128 and 426 genes respectively. Genes specifically expressed in stage Ib were totally 1329, including 482 upregulation genes and 847 downregulation genes, which were classified into different category which included 480 metabolism related genes, 227 signal transduction genes, 136 cell proliferation genes, 136 immune related genes, 94 cell adhere genes, 88 transcription regulation genes, 86 cell cycle genes, 73 cytoskeleton genes, 45 differentiation genes, 42 apoptosis and 31 extracellular matrix genes. RT-PCR examination of FOXM1 and TNXB genes was consistent with the analysis of gene chip. CONCLUSION: Stage Ib and IIIa Gene expression profile of primary SCC within the whole genome were set up and genes specifically expressed in stage Ib of SCC were identified, which lay a foundation for further research on carcinogenesis mechanism and identifying new markers of early diagnosis.

Carcinoma, Squamous Cell↗

Development and validation of a new index to measure emergency department crowding.

OBJECTIVES: To develop a quantitative measure of emergency department (ED) crowding and busyness. METHODS: A five-week study in spring 2002 in an urban teaching ED compared a new index (the Emergency Department Work Index [EDWIN]) with attending physician and nurse ratings of crowding. EDWIN is defined as summation operator n(i)t(i)/N(a)(B(T)-B(A)), where n(i) = number of patients in the ED in triage category i, t(i) = triage category, N(a) = number of attending physicians on duty, B(T) = number of treatment bays, and B(A) = number of admitted patients in the ED. The triage system used is the Emergency Severity Index (ESI), which was modified by reversing the ranking of triage categories; that is, an ESI score of 1 represented the least acute patient and 5 the sickest. EDWIN was calculated every two hours in a convenience sample of 60 eight-hour shifts. With each measurement, the charge attending physician and nurse estimated how busy/crowded the ED was, using a Likert scale. Nurse and physician assessments were averaged and compared with EDWIN scores. Data were analyzed with SPSS 10.0 (SPSS Inc., Chicago, IL). RESULTS: A total of 2,647 patients aged 18 years and older were assessed at 225 time points over 35 consecutive days. Nurses and physicians showed good interrater agreement of crowding assessment (weighted kappa 0.61, 95% confidence interval = 0.53 to 0.69). Median EDWIN scores and interquartile ranges (IQRs) when the ED was rated as not busy, average, and very busy were 1.07 (IQR = 0.80 to 1.55), 1.55 (IQR = 1.16 to 1.93), and 1.83 (IQR = 1.42 to 2.45) (p < 0.001). The ED was on diversion for 17 time blocks (6.5% of all blocks), with a median EDWIN of 2.77 (IQR = 1.83 to 3.63), compared with an EDWIN of 1.45 (IQR = 1.05 to 2.00) when not on diversion (p < 0.001). EDWIN scores correlated weakly with various process-of-care measures chosen as secondary end points. CONCLUSIONS: EDWIN correlated well with staff assessment of ED crowding and diversion. The index can be programmed into tracking software for use as a "dashboard" to alert staff when the ED is approaching crisis. If validated across other sites, EDWIN may provide a tool to compare crowding levels among different EDs.

Adult↗

Myocardial contrast echocardiography: relation between on-line and off-line assessment of myocardial perfusion.

BACKGROUND: Quantitative assessment of myocardial perfusion by myocardial contrast echocardiography has been made possible by the use of custom-made off-line video-intensity programs. A standardized program that could be used by all investigators would improve the reproducibility of results and enhance its clinical utility. METHODS AND RESULTS: The purpose of this study was to determine if the assessment of myocardial perfusion by contrast echocardiography using a new commercially available, quantitative on-line software program correlates with an off-line custom-made video-intensity program previously validated by our laboratory and with radiolabeled microspheres, under various experimental myocardial perfusion conditions. Two of the measured myocardial contrast echocardiographic parameters (peak intensity, area under the time-intensity curve {area}) correlated well among on-line and off-line methods and radiolabeled microspheres, especially when the data were "normalized" by comparing percent change from baseline or a ratio of ischemic to nonischemic myocardium. The third myocardial contrast echocardiographic parameter examined, half-time of the peak intensity on the washout limb of the curve (t 1/2), correlated only when the percent change from baseline was compared between the two methods or when the off-line method was compared with radiolabeled microspheres. CONCLUSION: The results of this investigation add further support to the potential use of myocardial contrast echocardiography to evaluate serial changes in myocardial perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

A critical evaluation of the electronic surgical logbook.

BACKGROUND: The Association of Surgeons of Great Britain and Ireland (ASGBI) devised the electronic surgical logbook (version 2.4) for higher trainees in General Surgery enabling trainees to compile a uniform data set of their operative and training experience. This is in use by higher surgical trainees (HST) in the United Kingdom. This logbook permits trainees to submit data centrally into a Regional Analysis Database (RAD). With the implementation of the European Working Time Directive (EWTD) there is need for reliable data to assess the effects of the directive on training. In order to draw meaningful conclusions from the database the quality of data needs to be validated. We critically analysed the RAD in the Yorkshire region for a one-year period. METHODS: The RAD from the ASGBI for the Yorkshire region was analysed. Data for the period 01/10/2002-30/09/2003 was identified and interrogated using Microsoft Excel (2000 version). The RAD was compared with information obtained from the Regional Surgical Advisor for Yorkshire with respect to hospitals, surgical consultants and HST's in the region during the study period. RESULTS: There were 13,755 operations entered for the study period. 579 corrections to the data had to be made (4.2%) and a further 1140 entries were deleted (8.2%). Following corrections and deletions 12,615 operative entries were available for analysis. Overall 12.5% of the data required either correction or exclusion from the database prior to analysis. CONCLUSION: The RAD has a large dataset useful to monitor and assess training. However, the quality of the data needs to be verified prior to use. Recommendations have been made to develop the ASGBI logbook, which would eventually translate to improved data reliability of the RAD.

Adult↗

Radiation biodosimetry: applications for spaceflight.

The multiparametric dosimetry system that we are developing for medical radiological defense applications could be adapted for spaceflight environments. The system complements the internationally accepted personnel dosimeters and cytogenetic analysis of chromosome aberrations, considered the best means of documenting radiation doses for health records. Our system consists of a portable hematology analyzer, molecular biodosimetry using nucleic acid and antigen-based diagnostic equipment, and a dose assessment management software application. A dry-capillary tube reagent-based centrifuge blood cell counter (QBC Autoread Plus, Becton [correction of Beckon] Dickinson Bioscience) measures peripheral blood lymphocytes and monocytes, which could determine radiation dose based on the kinetics of blood cell depletion. Molecular biomarkers for ionizing radiation exposure (gene expression changes, blood proteins) can be measured in real time using such diagnostic detection technologies as miniaturized nucleic acid sequences and antigen-based biosensors, but they require validation of dose-dependent targets and development of optimized protocols and analysis systems. The Biodosimetry Assessment Tool, a software application, calculates radiation dose based on a patient's physical signs and symptoms and blood cell count analysis. It also annotates location of personnel dosimeters, displays a summary of a patient's dosimetric information to healthcare professionals, and archives the data for further use. These radiation assessment diagnostic technologies can have dual-use applications supporting general medical-related care.

Animals↗

Development of a novel, simple and rapid molecular identification system for clinical Candida species.

Identification of clinical yeast isolates causing candidiasis is routinely performed by commercial yeast identification systems based on biochemical, morphological and physiological tests. These systems require 3-5 days and the proportion of identifications that are incorrect is high. Our novel and rapid molecular identification system for clinical Candida species is based on the analysis of restriction patterns obtained from PCR-generated ribosomal DNA sequences using five restriction enzymes. A software package (CandID) was designed to include a database of restriction fragment length polymorphism (RFLP) patterns for 29 Candida species. For 'in-house' validation, 122 clinical isolates that had previously identified in clinical laboratories were typed by this system. These clinical isolates were also independently re-identified by the API 20C AUX system. The ribosomal DNA RFLP database in the context of supporting analytical software allowed simple and rapid (1 work day) identification.

Candida↗

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗

Diagnostic DHPLC Quality Assurance (DDQA): a collaborative approach to the generation of validated and standardized methods for DHPLC-based mutation screening in clinical genetics laboratories.

Genetic testing in a clinical diagnostic environment must be subject to rigorous quality control procedures, in order to ensure consistency and accuracy of results. Denaturing high performance liquid chromatography (DHPLC) has become a standard prescreening tool for mutation detection, offering very high efficiency and sensitivity of detection. Despite the relatively simple software-assisted assay setup, DHPLC is a complex assay, and quality control is reliant on ensuring optimal instrument performance, excellent assay design and validation, and sufficient user training and proficiency to interpret results. We describe here a unique collaborative effort by a group of diagnostic clinical genetics laboratories with DHPLC expertise who, together with the manufacturer of one of the most widely used DHPLC platforms, have generated standard operating procedures (SOPs) for instrument operation and maintenance, and for mutation detection by DHPLC. We also describe the validation of a disease-specific SOP for DHPLC assisted mutation screening of the MECP2 gene associated with Rett syndrome. The proposed SOP was validated, and used independently in two laboratories to introduce MECP2 testing. In addition, we provide empirically derived normal ranges for the WAVE System Mutation Standards, which are essential for optimal instrument performance. This effort was initiated to try to standardize DHPLC-based mutation screening procedures across laboratories, and so increase the overall quality of this testing method. This endeavor will thus save each laboratory from having to generate SOPs on their own, which is a lengthy and laborious task. In this respect, we define "generic" SOPs as procedures that are easily adaptable to the individual laboratories' quality systems.

Chromatography, High Pressure Liquid↗

Feature extraction and normalization algorithms for high-density oligonucleotide gene expression array data.

Algorithms for performing feature extraction and normalization on high-density oligonucleotide gene expression arrays, have not been fully explored, and the impact these algorithms have on the downstream analysis is not well understood. Advances in such low-level analysis methods are essential to increase the sensitivity and specificity of detecting whether genes are present and/or differentially expressed. We have developed and implemented a number of algorithms for the analysis of expression array data in a software application, the DNA-Chip Analyzer (dChip). In this report, we describe the algorithms for feature extraction and normalization, and present validation data and comparison results with some of the algorithms currently in use.

Algorithms↗

Leveraging basecaller's move table to generate a lightweight k-mer model for nanopore sequencing analysis.

MOTIVATION: Nanopore sequencing by Oxford Nanopore Technologies (ONT) enables direct analysis of DNA and RNA by capturing raw electrical signals. Different nanopore chemistries have varied k-mer lengths, current levels, and standard deviations, which are stored in "k-mer models." In cases where official models are lacking or unsuitable for specific sequencing conditions, tailored k-mer models are crucial to ensure precise signal-to-sequence alignment, analysis and interpretation. The process of transforming raw signal data into nucleotide sequences, known as basecalling, is a fundamental step in nanopore sequencing. RESULTS: In this study, we leverage the move table produced by ONT's basecalling software to create a lightweight de novo k-mer model for RNA004 chemistry. We demonstrate the validity of our custom k-mer model by using it to guide signal-to-sequence alignment analysis, achieving high alignment rates (97.48%) compared to larger default models. Additionally, our 5-mer model exhibits similar performance as the default 9-mer models another analysis, such as detection of m6A RNA modifications. We provide our method, termed Poregen, as a generalizable approach for creation of custom, de novo k-mer models for nanopore signal data analysis. AVAILABILITY AND IMPLEMENTATION: Poregen is an open source package under an MIT license: https://github.com/hiruna72/poregen.

Nanopore Sequencing↗

[Comparison of three scales to assess health risk perception].

BACKGROUND: Health risks management consists of quantitative and qualitative assessment of risks including risk perception among different samples of the population. Little work has been done to develop and validate scales to measure risk perception. METHODS: We conducted, in December, 1999, a study among 1358 French GPs, members of the Sentinels network, in order to compare three scales: a visual analog scale, a verbal scale and a numerical scale. GPs were asked about their own perception of two risks: the Creutzfeldt-Jakob disease new variant (vMCJ) and the bug. RESULTS: The response rate was 55%, with no difference between the three groups (p=0.85). No statistically significant difference was observed between the distributions of the visual analog scale and the numerical scale (p=0.11 for the question about the vMCJ and p=0.98 for the question about the bug). Conversely, distributions of the verbal scale were significantly different from those of the visual analog scale (p<0.0001 for both of the questions) and from those of the numerical scale (p<0.0001 for both of the questions). Separation between worried and non worried people didn't occur in the middle of the visual analog scale but at 33 millimeters from the left extremity for the question about the vMCJ and at 41 millimeters from the same extremity for the question about the bug. CONCLUSION: We recommend the use of verbal scales to measure instantaneous perception of a given risk. Visual analog scales and numerical scales are known to be the best scales to detect minimum changes in the perception of functional signs such as pain. On this purpose, their superiority with regard to verbal scales has to be confirmed in the field of risk perception.

Attitude of Health Personnel↗

Computed tomography for assessment of cardiac chambers, valves, myocardium and pericardium.

The focus to date of MDCT has been primarily on CT applications for evaluating the coronary arteries, notably the measurement of coronary artery calcification, plaque characterization, and atherosclerotic lumen stenosis. This is because of the limited temporal resolution of CT, and the recent rapid improvements in MRI for cardiac applications. However, if the temporal resolution of MDCT can be improved, there will be a compelling argument for undertaking further CT validation studies. Feasibility of CT has already been established by EBT for general cardiac diagnosis. Modifications for MDCT include improved software methods for post processing ECG-gated scan data or higher speed CT hardware for faster image acquisition, both of which are being developed at this time. EBT is also evolving and continuously being refined so that the new generation of scanners have exposure times of 50 msec or less. There are many considerations in comparing the pros and cons of competing cardiac imaging modalities. Published diagnostic validations studies, convenience, procedure time, the comfort level (of patients and physicians), availability, and cost are all critical. The level of acceptance and the accuracy with which specific patient management questions can be appropriately answered are crucial issues in determining which diagnostic procedure to perform. However, the jury is still out regarding the ultimate role of CT in the diagnosis of heart disease; certainly the great potential of cardiac CT has not yet been fully realized.

Cardiomyopathies↗

Auto-rickshaw: an automated crystal structure determination platform as an efficient tool for the validation of an X-ray diffraction experiment.

The EMBL-Hamburg Automated Crystal Structure Determination Platform is a system that combines a number of existing macromolecular crystallographic computer programs and several decision-makers into a software pipeline for automated and efficient crystal structure determination. The pipeline can be invoked as soon as X-ray data from derivatized protein crystals have been collected and processed. It is controlled by a web-based graphical user interface for data and parameter input, and for monitoring the progress of structure determination. A large number of possible structure-solution paths are encoded in the system and the optimal path is selected by the decision-makers as the structure solution evolves. The processes have been optimized for speed so that the pipeline can be used effectively for validating the X-ray experiment at a synchrotron beamline.

Crystallography, X-Ray↗

Magnetic field visualization in applications to pulsed electromagnetic field stimulation of tissues.

Electromagnetic field visualization is important in multidisciplinary research on the molecular basis of therapeutic effects of pulsed electromagnetic fields (PEMF). We have compared classic PEMF representations by two-dimensional field lines and field magnitude contour plots with a field representation using three-dimensional field isosurfaces. Field simulations were performed for a clinically approved Spinal-Stim Lite system (Orthofix Inc., McKinney, TX). The relatively simple coil system geometry and the predominantly dielectric properties of the surrounding medium (air and human connective tissue) allowed us to develop analytical expressions for the field. The field model was validated by comparison with experimentally measured field values, and with values calculated using a commercial finite-element analysis software package. Two-dimensional field representations by field lines and field contour plots were less intuitive than three-dimensional field isosurface representations to members of the group without an engineering background. Field isosurfaces, represented as three-dimensional solids, allowed for direct visualization of PEMF targeting of individual organs (lumbar spine), the extent of the therapeutic field value, and the directional field characteristics. The dynamic characteristic of the field was well illustrated by a sequence of field isosurfaces corresponding to the evolution with time of the electric current waveform (sawtooth) powering the coils. The isosurface representation of the field can be extended to any three-dimensional coil system geometry using plotting capabilities of current computer algebra software packages.

Computer Simulation↗

Modeling of diffusion with partitioning in stratum corneum using a finite element model.

Partitioning and diffusion of chemicals in skin is of interest to researchers in areas such as transdermal penetration and drug disposition, either for risk assessment or transdermal delivery. In this study a finite element method is used to model diffusion in the skin's outermost layer, the stratum corneum (SC). The SC is considered to be a finite two-dimensional composite having different diffusivity values in each medium as well as a partition coefficient at the interfaces between media. A commercial finite element package with thermal analysis capabilities is selected due to the flexibility of this software to handle irregular geometries. Partitioning is accommodated through a change of variables technique. This technique is validated by comparison of model results with analytical solutions of steady-state flux, transient concentration profiles, and time lag for diffusion in laminates. Two applications are presented. Diffusion is solved in a two-dimensional "brick and mortar" geometry that is a simplification of human stratum corneum, with a partition coefficient between corneocyte and lipid. Results are compared to the diffusion in multiple laminates to examine effects of the partition coefficient. The second application is the modeling of diffusion with partitioning through an irregular geometry which is obtained from a micrograph of hairless mouse stratum corneum.

Administration, Cutaneous↗

Measurement of the electrically evoked compound action potential via a neural response telemetry system.

The main aim of this study was to validate a new technique, neural response telemetry (NRT), for measuring the electrically evoked compound action potential in adult cochlear implant users via their Nucleus C124M implant. Thirty-eight adults were evaluated with a variety of measurement procedures with the NRT software. Electrically evoked compound action potentials were obtained in 31 of the 38 adults (81.6%) and in 132 of the 160 electrodes (82.5%) tested. In addition to validating this technique, we also established a set of default clinical test parameters.

Action Potentials↗