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The functional organization of the isthmo-optic nucleus in the pigeon.

1. Extracellular single unit records were taken from the isthmo-optic nucleus of the pigeon, locating the nucleus by the antidromic field potential resulting from electrical stimulation of the isthmo-optic tract.2. Visual receptive fields were investigated for 248 units, and were classed into three types: directionally selective, directionally non-selective, and posterior minimum. They ranged from 3 to 10 degrees in extent.3. The topographical representation of the visual field in the nucleus was investigated by histological verification of electrode tracks, and a correlation with the receptive field sequences. Vertical descent through the nucleus resulted in an upwards progression of receptive field locations. Lateromedial passage through the nucleus resulted in a forwards progression of receptive field locations.4. The representation of the lower visual field is greater than that of the superior visual field: that for the central parts of the inferior field is greater than that for the periphery, and the representation of the anterior inferior quadrant is greater than that of the posterior inferior quadrant.

Animals↗

Evaluation of Kodak EDR2 film for dose verification of intensity modulated radiation therapy delivered by a static multileaf collimator.

A new type of radiographic film, Kodak EDR2 film, was evaluated for dose verification of intensity modulated radiation therapy (IMRT) delivered by a static multileaf collimator (SMLC). A sensitometric curve of EDR2 film irradiated by a 6 MV x-ray beam was compared with that of Kodak X-OMAT V (XV) film. The effects of field size, depth and dose rate on the sensitometric curve were also studied. It is found that EDR2 film is much less sensitive than XV film. In high-energy x-ray beams, the double hit process is the dominant mechanism that renders the grains on EDR2 films developable. As a result, in the dose range that is commonly used for film dosimetry for IMRT and conventional external beam therapy, the sensitometric curves of EDR2 films cannot be approximated as a linear function, OD = c * D. Within experimental uncertainty, the film sensitivity does not depend on the dose rate (50 vs 300 MU/min) or dose per pulse (from 1.0 x 10(-4) to 4.21 x 10(-4) Gy/pulse). Field sizes and depths (up to field size of 10 x 10 cm2 and depth = 10 cm) have little effect on the sensitometric curves. Percent depth doses (PDDs) for both 6 and 23 MV x rays were measured with both EDR2 and XV films and compared with ion chamber data. Film data are within 2.5% of the ion chamber results. Dose profiles measured with EDR2 film are consistent with those measured with an ion chamber. Examples of measured IMRT isodose distributions versus calculated isodoses are presented. We have used EDR2 films for verification of all IMRT patients treated by SMLC in our clinic. In most cases, with EDR2 film, actual clinical daily fraction doses can be used for verification of composite isodose distributions of SMLC-based IMRT.

Adult↗

Innovative safety valve selection techniques and data.

The new valve data resources and modeling tools that are available today are instrumental in verifying that that safety levels are being met in both current installations and project designs. If the new ISA 84 functional safety practices are followed closely, good industry validated data used, and a user's maintenance integrity program strictly enforced, plants should feel confident that their design has been quantitatively reinforced. After 2 years of exhaustive reliability studies, there are now techniques and data available to support this safety system component deficiency. Everyone who has gone through the process of safety integrity level (SIL) verification (i.e. reliability math) will appreciate the progress made in this area. The benefits of these advancements are improved safety with lower lifecycle costs such as lower capital investment and/or longer testing intervals. This discussion will start with a review of the different valve, actuator, and solenoid/positioner combinations that can be used and their associated application restraints. Failure rate reliability studies (i.e. FMEDA) and data associated with the final combinations will then discussed. Finally, the impact of the selections on each safety system's SIL verification will be reviewed.

Accident Prevention↗

How to improve ischemic stroke treatment in the fibrinolysis era.

In the last 15 years new therapeutic approaches have influenced the treatment of ischemic stroke victims. Aim of this review is to point out the elements of a modern approach to the acute stroke patient. The likelihood of saving ischemic cerebral tissue is time-dependent and the treatment goal is to minimise brain damage. The NINDS trial has documented a higher likelihood of better outcome if the fibrinolytic therapy is administered within 3 h of onset of symptoms. To reach this target several interventions are necessary. First of all, education is needed to diffuse public awareness of stroke warning signs. Moreover, out-of-hospital treatment should be optimised with rapid triage and transport to an hospital with a comprehensive stroke approach. The early hospital phase should comprehend a rapid evaluation and an urgent CT scan. After the verification of the inclusion/exclusion criteria, in a authorised SITS-MOST centre, the patient should receive fibrinolytic therapy. The diagnostic and the therapeutic phase should include rapid identification and treatment of secondary insults, as hyperthermia and hyperglycaemia, that have a negative influence on outcome. Despite advances in diagnosis and monitoring, fibrinolytic therapy is the only treatment with a proven efficacy in achieving a higher functional outcome. The narrow time-window is the reason for the need of rapid and well-organised out-of-hospital and in-hospital systems.

Brain Ischemia↗

Verification of inverse planning and treatment delivery for segmental IMRT.

With intensity-modulated radiotherapy (IMRT), it is important that the inverse planning process yields the most appropriate dose distribution for the patient and that the delivered dose then corresponds to the planned dose. This paper presents methods by which the inverse planning and delivery of segmental (step-and-shoot) IMRT can be verified, and gives results for a typical treatment planning system (Pinnacle3 v6.2b, Philips Radiation Oncology Systems, Milpitas, CA). Inverse planning was assessed by observing the reduction in objective function as fields were successively added to three-field prostate, esophagus, and thyroid plans. The ability of the treatment planning system to calculate dose for a segmented field was examined by creating a stepped field with five successively narrowing segments. The complete planning process was then investigated by using two orthogonal IMRT fields to create a homogeneous dose distribution in a cubic water phantom. Finally, a clinical situation was simulated by creating a five-field segmental IMRT plan for a lung target in an anthropomorphic phantom. A conformal plan was also compared for context. Addition of fields to inverse plans generally resulted in a reduction of objective function, indicating consistency of inverse planning solutions. Planned dose for fields with stepped intensity agreed with ionization chamber measurements to within 5%. For orthogonal fields, planned dose distributions agreed well with dose measured using film and agreed with ionization chamber measurements to within 3%. For the anthropomorphic phantom, the standard deviation of difference between planned and measured dose was 4%. Although no consensus has yet been reached on what constitutes an acceptable IMRT plan, these results indicate that step-and-shoot IMRT can be planned and delivered using the system described with comparable accuracy to a standard conformal treatment.

Algorithms↗

Effect of verification bias on positive and negative predictive values.

The pairing of sensitivity and specificity expresses the efficacy of a test, and positive and negative predictive values measure the accuracy of a diagnostic test when applied to a particular patient. To calculate these measures, one has to know the true disease status of each patient. In practice, however, some patients may not be selected for verification of disease status. It has been shown that the estimated sensitivity and specificity may be biased if one includes in the study sample only the patients with verified disease statuses. This paper concerns the properties of the estimators of positive and negative predictive values using only patients with verified disease statuses. First, I show that these estimators are unbiased and provide consistent estimators for the variances of these estimators under the assumption that the probability of selecting a patient for a disease verification procedure does not depend directly on the true disease status of the patient. Then, I use the ML method to study the sensitivity of the naive estimators to the departure from the conditional independence assumption.

Bias↗

Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated conditions.

We previously reported that a soluble form of the TNF-family receptor death receptor-3 (DR3) is expressed in osteoblasts. DR3 regulates death or differentiation in other tissues, and DR3 ligands occur in bone, but the function of DR3 in the osteoblast was unknown. We studied the expression of DR3 and the effects crosslinking antibodies to DR3 or of natural DR3 ligands in human osteoblasts. Western analysis showed that nontransformed osteoblasts and the MG63 osteosarcoma cell line produce both soluble decoy receptor and transmembrane isoforms of DR3. Cell surface labeling showed that low and high DR3-expressing osteoblast populations occur. Verification of by cloning showed a point mutation in DR3 from MG63 cells. Activation of DR3 by antibody crosslinking or with DR3 ligands caused apoptosis in osteoblasts and in MG63 cells, but only in low-density cell cultures. In dense cultures apoptosis did not occur, but nuclear factor-kappaB nuclear translocation was observed under some conditions. Crosslinking of DR3 in high-density MG63 cultures blocked expression of bone matrix elements. DR3 activation in high-density nontransformed osteoblasts had only minor effects on cell maturation. We conclude that DR3 activation can mediate apoptosis in osteoblasts. Its activity is, however, highly restricted by its soluble ligand-binding isoform and possibly also by alternate survival signals. In the presence of survival signals, DR3 may affect cell maturation although effects on differentiation were clearly seen only in the MG63 transformed cell line.

Animals↗

Analysis of creatine and creatinine in urine by capillary electrophoresis.

Creatine is found in the urine of subjects ingesting creatine monohydrate as an ergogenic aid. Creatinine, the catabolic breakdown product of creatine, is a major constituent of normal urine. It is of interest to follow the excretion of creatine and creatinine in urine as a function of time after creatine ingestion. In this study, creatine and creatinine were analyzed in urine by capillary electrophoresis. The optimization of the method was discussed, with the best results being obtained using a 30 mM phosphate-150 mM sodium dodecyl sulfate buffer at pH 6, with the detector set at 214 nm and an applied voltage of 15 kV across a 45 cm capillary. Verification of the method was provided by HPLC analysis and spiking. The application of the method was demonstrated by analysis of creatine and creatinine in urine samples collected in a 24-h period following creatine ingestion.

Calibration↗

Evaluation of mobile decentralized pharmaceutical services in a community teaching hospital.

Mobile decentralized pharmaceutical services were compared with the previous centralized unit dose drug distribution services in a community teaching hospital. Medication order turnaround time, pharmacist workload activities, number of drug information requests, dose-activity index, and quality of drug distribution and drug administration record keeping were compared under the two systems. The number of drug therapy problems identified and resolved by decentralized pharmacists also was determined. Medication order turnaround time decreased from a mean of 198 minutes to 64 minutes in the centralized and decentralized systems, respectively. The number of drug information requests increased from 0.0055 to 0.05 requests per patient day. The percentage of requests related to adverse drug reactions, drug interactions, therapeutics, pharmacokinetics, and pharmacology increased in the decentralized system. The dose-activity index was 63.5% and 56.9% for centralized and decentralized systems, respectively, with the mean number of doses handled per patient day at 14.4 and 10.7. Decentralized pharmacists spent substantially more time than centralized pharmacists performing educational, therapy-related, and dispensing activities and less time performing clerical and verification activities. Decentralized pharmacists detected a large number of drug therapy problems that probably would have gone undetected in the previous system. The decentralized system met 31 of the 32 quality assurance standards, compared with 20 standards met for the centralized system. The implementation of mobile decentralized services provided greater opportunities for use of the pharmacists' clinical skills and reduced the time allocated to traditional functions.

Drug Information Services↗

Technical considerations for fractionated stereotactic radiotherapy of hepatocellular carcinoma.

Technical aspects of fractionated stereotactic radiotherapy for solitary hepatocellular carcinoma have been investigated. Precise positioning of the patient and substantial reduction of the liver movement due to respiration were achieved by placing the patient ventrally on the treatment couch without a body cast. Repeated CT examinations were required for verification of tumor targeting. Though there were geometrical limitations on gantry rotation when the linac couch was rotated from its standard position, dose distributions obtained were found to be excellent. A patient with a small solitary lesion in the posterior segment of the liver received 52 Gy in 13 fractions over 29 days. He tolerated the treatment well without experiencing any morbidities or deterioration of liver functions. Three months later his alpha-fetoprotein value returned to normal and CT examinations revealed tumor shrinkage as well as a reduction in the viability of the tumor cells. The results suggest that it is possible to overcome technical difficulties associated with fractionated stereotactic radiotherapy of intraabdominal tumors.

Aged↗

Reevaluating human gene annotation: a second-generation analysis of chromosome 22.

We report a second-generation gene annotation of human chromosome 22. Using expressed sequence databases, comparative sequence analysis, and experimental verification, we have extended genes, fused previously fragmented structures, and identified new genes. The total length in exons of annotation was increased by 74% over our previously published annotation and includes 546 protein-coding genes and 234 pseudogenes. Thirty-two potential protein-coding annotations are partial copies of other genes, and may represent duplications on an evolutionary path to change or loss of function. We also identified 31 non-protein-coding transcripts, including 16 possible antisense RNAs. By extrapolation, we estimate the human genome contains 29,000-36,000 protein-coding genes, 21,300 pseudogenes, and 1500 antisense RNAs. We suggest that our revised annotation criteria provide a paradigm for future annotation of the human genome.

Animals↗

Vectorial modal analysis of dielectric waveguides based on a coupled transverse-mode integral equation. II. Numerical analysis.

We present numerical implementation and verification of a rigorous full-vector, integral-equation formulation suitable for analyzing modal characteristics of complex, two-dimensional (2D) rectangular-like dielectric waveguides. By dividing the waveguide into vertical slices, a system of integral equations we call vector-coupled transverse-mode integral equations (VCTMIE) is derived. The entire electromagnetic mode fields are completely determined by one-dimensional unknown field functions on the slice interfaces. To further reduce numerical computation, we expand these functions in terms of the guiding modes of a slab waveguide with a large normalized frequency. Through orthogonal projection the resulting nonlinear eigenvalue and eigenvector matrix formulation enables us to obtain the effective mode index with 10(-7) precision and to compute with high resolution the 2D vectorial mode field solutions of an open dielectric waveguide. We show stable and speedy convergence of our method as well as techniques to overcome the Gibbs phenomenon in the reconstruction of the transverse fields.

Journal Article↗

[Chronic asthmatic bronchitis].

The main pathogenetic mechanisms and morphological picture of chronic asthmatic bronchitis are similar to those of bronchial asthma. The only difference is the absence of regular fits of asphyxia. Diagnosis of this disease is based upon the detection of the broncho-obstructive syndrome and verification of its allergic origin. Therapy of chronic asthmatic bronchitis is based on the same principles as that of bronchial asthma.

Adult↗

Genome data mining of lactic acid bacteria: the impact of bioinformatics.

Lactic acid bacteria (LAB) have been widely used in food fermentations and, more recently, as probiotics in health-promoting food products. Genome sequencing and functional genomics studies of a variety of LAB are now rapidly providing insights into their diversity and evolution and revealing the molecular basis for important traits such as flavor formation, sugar metabolism, stress response, adaptation and interactions. Bioinformatics plays a key role in handling, integrating and analyzing the flood of 'omics' data being generated. Reconstruction of metabolic potential using bioinformatics tools and databases, followed by targeted experimental verification and exploration of the metabolic and regulatory network properties, are the present challenges that should lead to improved exploitation of these versatile food bacteria.

Adaptation, Biological↗

Questions about the uncertain presence of muscle spindles in the human external anal sphincter.

The verification of the uncertain presence of muscle spindles in the external anal sphincter is important in the comprehension of the pathophysiology of continence. The authors failed to demonstrate these proprioceptive structures in 10 human sphincters examined with different histological techniques, whereas they found some typical muscle spindles in the puborectalis muscles. The possible interpretations of the different results on the subject in the literature together with their functional implications are discussed.

Adult↗

A test to establish maximum O2 uptake despite no plateau in the O2 uptake response to ramp incremental exercise.

The O2 uptake (Vo2) response to ramp incremental (RI) exercise does not consistently demonstrate plateau-like behavior at the limit of tolerance, and hence the requirements for a maximum Vo2 commonly are not met, despite apparent maximum effort. We sought to determine whether an appended step exercise (SE) test at a work rate greater than that achieved in a preceding ramp test would establish the plateau criterion. Seven healthy male adults performed RI cycle ergometry (20 W/min) to the limit of tolerance, followed by 5-min recovery (20 W) and then an SE test at 105% (RISE-105) of the final work rate (WRpeak) achieved during RI. Five of these subjects also performed an RI test followed by SE at 95% WRpeak (RISE-95). Vo2 was measured breath by breath using a turbine and mass spectrometer. The average of the final 15 s of RI or SE was used to establish respective Vo2 peaks. When Vo2 peak was approached, a constant Vo2 value (e.g., a plateau) was not discernable during any RI or SE component of the tests. Although the WRpeak [mean (SD)] was higher during the SE portion [359 W (SD 31)] than during the RI portion [341 W (SD 29)] of the RISE-105, the peak Vo2 was not different [SE, 4.30 l/min (SD 0.51); RI, 4.33 l/min (SD 0.52); P=0.49; n=7]. Similarly, in the RISE-95 test, WRpeak was 310 W (SD 31) for the SE portion and 326 W (SD 32) for the RI portion, yet the peak Vo2 values were not different [SE, 4.12 l/min (SD 0.53); RI, 4.11 l/min (SD 0.48); P=0.78; n=5]. The lack of notable difference between the Vo2 peaks established at different WRpeak values in our RISE protocols provides the plateau criterion for verification of maximum Vo2 in a single test session, even when the data response profiles do not themselves evidence a plateau.

Adult↗

Genetic analysis of progenitor cell mobilization by granulocyte colony-stimulating factor: verification and mechanisms for loci on murine chromosomes 2 and 11.

OBJECTIVE: It is notable that there is significant inter-individual variability in humans and inter-strain variability in mice in the ability to mobilize hematopoietic stem and progenitor cells, suggesting that there is genetic regulation of mobilization. In the murine system, loci on chromosomes 2 and 11 have been linked to an inter-strain variation in granulocyte colonystimulating factor (G-CSF)-induced stem cell mobilization proficiency. The aim of this study was to verify this linkage and to gain insight into the function of these loci. METHODS: Animals congenic for the loci on chromosomes 2 and 11 were generated by a speed-congenic approach and the function of the loci were further analyzed in doubly congenic animals and with a competitive transplantation/mobilization protocol. RESULTS: The analysis of congenic animals verified that both loci are linked to mobilization proficiency. Analysis of mobilization in doubly congenic animals suggested that both loci act in the same regulatory pathway. Mobilization experiments conducted with mice that had previously been competitively repopulated with congenic and parental-strain BM revealed that the locus on chromosome 11 operates via a progenitor cell-intrinsic mechanism. CONCLUSION: We confirmed linkage of loci on chromosomes 2 and 11 to G-CSF-induced mobilization and thus validated their role as regulators of hematopoietic progenitor cell mobilization in mice. These findings will be useful for further studies directed at identifying genes that regulate mobilization proficiency.

Animals↗

[Assessment of the anti-ischemic effect in patients with therapy refractory angina pectoris in end-stage coronary heart disease--results of chronic intermittent urokinase therapy].

Patients with refractory angina pectoris and end-stage coronary artery disease represent an increasing clinical problem. Numbers of these patients will increase in the future for improved survival due to effective secondary prevention of coronary artery disease. Next to the evaluation of clinical symptoms non-invasive objective parameters of myocardial ischemia are of major relevance before initiation of alternative treatment modalities and for verification of antiischemic effectiveness. Based on our own experience it can be shown that in these patients testing which is mainly based on the patients physical exercise capacity is only of limited value due to the early occurrence of clinical symptoms. Furthermore diffuse perfusion abnormalities reduce the sensitivity of electrocardiographic and scintigraphic detection of ischemic changes. In contrast indirect measures of ischemia relating to the systolic or diastolic function of the left ventricle like doppler-echocardiography and radionuclide ventriculography seem to be promising approaches. This is confirmed by the results from the application of long-term intermittent urokinase therapy. Long-term intermittent urokinase therapy leads to an absolute enhancement of myocardial perfusion, which makes this approach superior to other medical interventions which are mainly based on a reduction of cardiac work-load.

Angina Pectoris↗