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Experimental verification of the correlation behavior of analytic ultrasound radiofrequency signals received from moving structures.

Conventional pulsed ultrasound systems are only able to detect motion along the ultrasound beam (i.e., axial motion). If the angle between the actual motion direction and the ultrasound beam is known, then the magnitude of the actual motion can be derived. This technique can be applied for laminar blood-flow measurements in straight vessels, but for tissue motion it is inadequate because the local tissue motion direction is unknown and may be position-dependent. Assessment of both the axial motion and the lateral motion (i.e., in the direction perpendicular to the ultrasound beam) makes angle-independent assessment of the magnitude of the actual motion feasible. Information about the axial and lateral motion is available in a set of radiofrequency (RF) signals obtained along the same line of observation (M-mode). The experiments described in the present paper show that axial and lateral motion can be estimated from the shape of the envelope of the 2-D (spatial and temporal) correlation function of analytic M-mode RF signals. Furthermore, it is demonstrated that the shape is also affected by the Band width of the received RF signals, signal-to-noise ratio, and local amplitude and phase characteristics of the ultrasound beam.

Humans↗

Temporal lobe epilepsy: evidence for interictal uncoupling of blood flow and glucose metabolism in temporomesial structures.

Measurements of regional cerebral glucose metabolism (rCMRGlc) and blood flow (rCBF) are widely considered exchangeable for the detection of dysfunctional zones in temporal lobe epilepsy (TLE). However, the underlying assumption of preserved coupling of rCBF and rcMRGlc is questionable and requires verification. Thirteen patients with unilateral mesiolimbic TLE underwent interictal positron emission tomography (PET) measurements of rCBF using [15(O)]butanol and of rcMRGlc using (18)FDG. rcMRGlc, rCBF and glucose extraction fraction (rGEF) were obtained from temporomesial and temporolateral structures. When compared to the respective homotopic contralateral reference region, in temporomesial structures ipsilateral to the EEG-defined focus ('dysfunctional zone'), average rCMRGlc and rGEF were decreased while rCBF was unaffected. Analysis of (18)FDG kinetics revealed that (18)FDG transport was unaltered but the hexokinase reaction was specifically decreased. In the temporolateral structures, no such mismatch between metabolism and blood flow was observed. In mesiolimbic TLE, interictal rCMRGlc-PET is superior to rCBF-PET with respect to the sensitivity to detect regional functional abnormalities. This seems to be due to focal uncoupling of glucose metabolism and blood-brain barrier transport or blood flow. We hypothesize that the observed uncoupling of transport and metabolism may be characteristic of epileptogenic zones in TLE of typical etiology.

Adult↗

The calculating brain: an fMRI study.

To explore brain areas involved in basic numerical computation, functional magnetic imaging (fMRI) scanning was performed on college students during performance of three tasks; simple arithmetic, numerical magnitude judgment, and a perceptual-motor control task. For the arithmetic relative to the other tasks, results for all eight subjects revealed bilateral activation in Brodmann's area 44, in dorsolateral prefrontal cortex (areas 9 and 10), in inferior and superior parietal areas, and in lingual and fusiform gyri. Activation was stronger on the left for all subjects, but only at Brodmann's area 44 and the parietal cortices. No activation was observed in the arithmetic task in several other areas previously implicated for arithmetic, including the angular and supramarginal gyri and the basal ganglia. In fact, angular and supramarginal gyri were significantly deactivated by the verification task relative to both the magnitude judgment and control tasks for every subject. Areas activated by the magnitude task relative to the control were more variable, but in five subjects included bilateral inferior parietal cortex. These results confirm some existing hypotheses regarding the neural basis of numerical processes, invite revision of others, and suggest productive lines for future investigation.

Adult↗

Trueness verification in European external quality assessment schemes: time to care about the quality of the samples.

An external quality assessment (EQA) survey on 14 fresh-frozen, single-donation sera assigned with reference measurement procedure (RMP) values revealed a mean bias of + 5.2% and + 3.7% for the cholesterol oxidase and the photometric glucose oxidase procedure groups, respectively. Conversely, on lyophilized sera, the same procedure groups showed almost bias-free results, the differences from the RMP values being only -0.8% for cholesterol and + 0.7% for glucose. These data, which are in fairly good agreement with the literature, suggest the existence of artificial matrix effects in processed materials. Therefore they indicate that, currently, assessment of trueness is hampered in many European EQA schemes, as most of them use lyophilized sera. This approach may give a false impression about the trueness of laboratory results as well as carrying the risk that laboratories calibrated on the RMP values of the survey samples could make errors in patient testing. Consequently, if European EQA is willing to fulfil a post-market vigilance function of the performance of in vitro diagnostic medical devices, then the time has come to tackle the problem of the quality of the survey samples. EQA organizers urgently need to make an effort to seek out materials that analytically behave like authentic clinical specimens. In the meantime, alternative approaches should be used. Although not ideal, the special survey described in this article is one of the possibilities. Naturally, it implies logistic problems and increased costs for the individual EQA schemes. However, both can be overcome with the cooperation of the predominantly nationally organized schemes.

Blood Glucose↗

MICheck: a web tool for fast checking of syntactic annotations of bacterial genomes.

The annotation of newly sequenced bacterial genomes begins with running several automatic analysis methods, with major emphasis on the identification of protein-coding genes. DNA sequences are heterogeneous in local nucleotide composition and this leads sometimes to sequences being annotated as authentic genes when they are not protein-coding genes or are true but uncharacterized protein-coding genes. This first annotation step is generally followed by an expert manual annotation of the predicted genes. The genomic data (sequence and annotations) organized in an appropriate databank file format is subsequently submitted to an entry point of the International Nucleotide Sequence Database. These procedures are inevitably subject to mistakes, and this can lead to unintentional syntactic annotation errors being stored in public databanks. Here, we present a new web program, MICheck (MIcrobial genome Checker), that enables rapid verification of sets of annotated genes and frameshifts in previously published bacterial genomes. The web interface allows one easily to investigate the MICheck results, i.e. inaccurate or missed gene annotations: a graphical representation is drawn, in which the genomic context of a unique coding DNA sequence annotation or a predicted frameshift is given, using information on the coding potential (curves) and annotation of the neighbouring genes. We illustrate some capabilities of the MICheck site through the analysis of 20 bacterial genomes, 9 of which were selected for their 'Reviewed' status in the National Center for Biotechnology Information (NCBI) Reference Sequence Project (RefSeq). In the context of the numerous re-annotation projects for microbial genomes, this tool can be seen as a preliminary step before the functional re-annotation step to check quickly for missing or wrongly annotated genes. The MICheck website is accessible at the following address: http://www.genoscope.cns.fr/agc/tools/micheck.

Computer Graphics↗

Immune consequences of stroke and cerebral palsy in adults.

The possibility that brain damage results in a sustained dysregulation of lymphocyte responsiveness to the lymphokine, interleukin-2 (IL-2), was investigated in individuals who had experienced a unilateral stroke in adulthood or who presented with spastic hemiparesis since childhood. Following verification of unilateral brain damage via neuromotor assessment, and determination of their health status, blood samples were obtained to evaluate a panel of immune measures. Soluble interleukin-2 receptor (sIL-2R) and lymphocyte proliferative and cytolytic responses in the subjects with stroke or cerebral palsy were compared to age- and gender-matched controls. In addition, lymphocyte populations were enumerated via flow cytometry, and lymphocyte cyclic AMP (cAMP) levels were determined. Circulating blood levels of sIL-2R were significantly elevated in all individuals that had experienced unilateral brain damage. Cytolytic activity also failed to be stimulated to the normal level by in vitro treatment of lymphocytes with IL-2. Further, lymphocytes from the stroke subjects proliferated significantly less after mitogen and IL-2 stimulation. These functional differences were not accounted for by an abnormal leukocyte profile, although phenotypic analyses revealed subtle differences in the natural killer cell subsets. Overall, the findings indicate that individuals with brain damage may not respond appropriately when immune activation is required. These immune differences appear to be a stable trait given that they were manifested after both perinatal and adult brain insult in otherwise healthy, independently living individuals.

Activities of Daily Living↗

Validation of a tracer kinetic model for the quantification of 5-HT(2A) receptors in human brain with [(11)C]MDL 100,907.

The positron emission tomography (PET) ligand [(11)C]MDL 100,907 has previously been introduced to image the serotonin 2A (5-HT(2A)) receptor in human brain. The aim of this work was to contribute to the verification of the tracer kinetic modelling in human studies. Five healthy volunteers were scanned twice after intravenous bolus injection of approximately 370 MBq [(11)C]MDL 100,907 using dynamic PET. One scan was performed under baseline condition, the other scan commenced 90 mins after a single oral dose of 30 mg of the antidepressant mirtazapine, which binds to the 5-HT(2A) receptor. There did not appear to be radiolabelled metabolites of [(11)C]MDL 100,907 in human plasma, which are likely to cross the blood-brain barrier. Total volumes of distribution VD in 11 different brain regions were estimated using a reversible, two tissue, four rate constants compartment model with a variable fractional blood volume term and the metabolite-corrected plasma input function. There were no significant changes of the VD in the cerebellum between the baseline and the blocked scans confirming the cerebellum as a region devoid of displaceable binding. Regional estimates of binding potential were then obtained indirectly using the cerebellar VD and occupancies calculated. The mean occupancy with this clinically effective dose of mirtazapine was 60% without significant regional differences. This study confirmed the use of an arterial input kinetic model for the quantification of 5-HT(2A) receptor binding with [(11)C]MDL 100,907 and the use of the cerebellum as a reference region for the free and nonspecific binding.

Adult↗

A dynamic model of the behaviour of sitka spruce in high winds

This paper describes the development, verification and use of a mathematical model to describe the dynamic behaviour of typical forest trees in high winds. The model assumes (a) that the trunk can be represented by a vertical tapered cantilever with specified stiffness and mass distributions; (b) that the canopy can be represented by a cylindrical body of a different density at the top of the trunk; (c) that the wind loading can be represented by a spatially constant wind distribution applied to the upper part of the canopy, that is varying in time with realistic spectral properties; (d) that the damping of the oscillations of the tree is caused solely by aerodynamic damping.The resulting complex, fourth-order differential equations are solved using numerical methods. This model is used to predict the transfer functions relating tree displacement spectra to wind spectra, and it is shown that the model is able to represent experimental spectra well, particularly with regard to the prediction of the primary natural frequency. Wind speeds for tree failure by both trunk snapping and uprooting are then pictured, and reasonably realistic values obtained. The need for a better understanding of the relationship between extreme and mean wind gusts is apparent. Through a discussion of the sensitivity of the results to variations in the different model parameters some general conclusions are drawn about the effects of the different parameters on tree stability. Copyright 1999 Academic Press.

Journal Article↗

An Active Matrix Flat Panel Dosimeter (AMFPD) for in-phantom dosimetric measurements.

An a-Si Active Matrix Flat Panel Imager (AMFPI) prototype developed in-house has been modified to function as an in-phantom dosimetry system providing high resolution two-dimensional (2-D) data. This Active Matrix Flat Panel Dosimeter (AMFPD) system can be used as a replacement device for standard in-phantom dosimeters, such as scanning ion chambers in water, or film in solid water. The initial characterization of the device demonstrates a wide dynamic range (up to 160 cGy), a stable calibration curve (less than 1.5% variation over 1 year), dose rate independence (less than 1%), and excellent agreement of output factors with ion chamber measurements for a range of field sizes (less than 2%). The device also compares well to film for 2-D planar dose distributions. It is expected that the AMFPD system will be useful for beam commissioning, algorithm verification test data, and routine IMRT quality assurance dosimetry.

Equipment Design↗

A cardiac evoked response algorithm providing automatic threshold tracking for continuous capture verification: a single-center prospective study.

BACKGROUND: The AutoCapture algorithm as implemented in Regency and Microny pacemakers (Pacesetter Inc., Sylmar, CA, USA) provides beat-by-beat monitoring of capture based on proper detection of the evoked response, provides high output back-up pulse when loss of capture occurs, performs periodic threshold evaluations and acquires the capture threshold data in a time-based event counter for later retrieval. The safety and efficacy of this algorithm was prospectively evaluated at a tertiary care hospital of north India. METHODS AND RESULTS: Fifty-four patients (38 males, mean age 66+/-13 years) received a ventricular pacemaker model Regency SC+ with low polarization bipolar lead for high-grade atrioventricular block (n=42) and sick sinus syndrome (n=12). Evoked response and polarization signal were assessed initially at 24 hours postimplant, and follow-up measurements were systematically conducted at week 1 and months 1, 3 and 6. Further evaluation of eligible patients was performed at 6-monthly intervals. Lead implantation parameters were optimum in all patients. At 6 months, the algorithm was functional in 51 patients. The pacing threshold increased to 0.89+/-0.36 V (p<0.001) in the first month and stabilized thereafter. Significant saving of energy was accomplished by a constant output safety margin of 0.3 V instead of the traditional 100%. While the evoked response signal remained stable throughout the study period, the potential signal increased significantly from 0.6+/-0.7 mV to 1.0+/-0.6 mV (p<0.001) in the first month and remained steady subsequently. Back-up pacing in the event of exit block was confirmed in all 25 patients who underwent a 24-hour Holter test. Based on the suggested sense margins, ventricular undersensing was observed in 7 (28%) patients, the majority of whom had competitive cardiac rhythms. An elderly patient with pneumonic illness succumbed to pulmonary embolism at 6 months. CONCLUSIONS: This large single-center experience on AutoCapture demonstrates the success of this algorithm in low-energy ventricular pacing without compromising the patient's safety.

Adolescent↗

Cloning, molecular and functional characterization of Arabidopsis thaliana allene oxide synthase (CYP 74), the first enzyme of the octadecanoid pathway to jasmonates.

Allene oxide synthase, an enzyme of the octadecanoid pathway to jasmonates, was cloned from Arabidopsis thaliana as a full-length cDNA encoding a polypeptide of 517 amino acids with a calculated molecular mass of 58705 Da. From the sequence, an N-terminal transit peptide of 21 amino acids resembling chloroplast transit peptides was deduced. Three out of four invariant amino acid residues of cytochrome P450 heme-binding domains are conserved and properly positioned in the enzyme coding region, including the heme-accepting cysteine (Cys-470). Southern analysis indicated in A. thaliana only one allene oxide synthase gene to be present. While transcript levels were rapidly and transiently induced after wounding of the leaves, allene oxide synthase activity remained nearly constant at a low level of ca. 0.8 nkat per mg of protein. The cDNA encoding A. thaliana allene oxide synthase was highly expressed in bacteria giving rise to a polypeptide of the calculated molecular mass. The protein was enzymatically active, and verification of the reaction products by GC-MS showed that it was capable of utilizing not only 13-hydroperoxylinolenic acid (13-hydroperoxy-9(Z), 11(E), 15(Z)-octadecatrienoic acid), but also 13-hydroperoxylinoleic acid (13-hydroperoxy-9(Z), 11(E)-octadecadienoic acid) as substrate. The data suggest parallel pathways to jasmonates from linolenic acid or linoleic acid in A. thaliana.

Amino Acid Sequence↗

vALId: validation of protein sequence quality based on multiple alignment data.

The validation of sequences is essential to perform accurate phylogeny and structure/function analysis. However among the thousands of protein sequences available in the public databases, most have been predicted in silico and have not systematically undergone a quality verification. It has recently become evident that they often contain sequence errors. To address the problem of automatic protein quality control, we have developed vALId, an interactive web interfaced software. Taking advantage of high quality multiple alignments of complete protein sequences (MACS), vALId first warns about the presence of suspicious insertions, deletions (indels) and divergent segments, and second, proposes corrections based on transcripts and genome contigs. In a first evaluation test, hundreds of indels and divergent segments were randomly generated in a manually refined MACS. The sensitivity (Sn) and specificity (Sp) of indel detection were excellent (0.96) while the mean Sn(0.49) and Sp(0.56) of divergent segment delineation depended on the percent identity between sequence neighbors. In a second test, 6195 sequences in 100 MACS corresponding to different functional and structural protein families were analyzed. 65% of the sequences were in silico predictions and 44% of eukaryote predicted proteins were partially incorrect with at least one suspicious indel or divergent segment.

Algorithms↗

Cystic vestibular schwannoma: surgical outcome.

We investigated the proportion of the cystic form of vestibular schwannoma and assessed the results of surgery in this subtype of the condition. The definition of cystic vestibular schwannomas was based on the following criteria: per-operative identification of cystic components; occurrence of the hypodense/hypointense areas on computed tomography (CT) and/or magnetic resonance (MR); and histological verification of S-100 protein membrane-like structures. In a study of 773 Danish patients with vestibular schwannomas, 44 (5.7 per cent) displayed cystic components. The outcome of surgery on 44 cystic vestibular schwannoma (mean tumour size 39 mm) was evaluated and compared with that for 151 solid grant vestibular schwannoma (mean tumour size 49.8 mm). Per-operatively, we found a substantially higher adherence to different intracranial structures in the solid giant vestibular schwannoma compared with the cystic vestibular (95 per cent vs 70 per cent for brainstem, 91 per cent vs 59 per cent for trigeminal nerve, 85 per cent vs 45 per cent for cranial nerves X and XI, 67 per cent vs 32 per cent for dura). Nevertheless, the preservation of the facial nerve function was much better in patients with solid giant vestibular schwannoma compared with those with cystic vestibular schwannoma (House-Brackmann facial nerve dysfunction grade 6 (one year post-operative): 27 per cent vs 41 per cent, respectively p < 0.04). We conclude that the cystic components in vestibular schwannoma are associated with a less favourable surgical outcome, probably due to the rapid tumour growth and symptoms caused by compression of the posterior fossa structures.

Adult↗

[The aged heart in surgery].

The risk of surgical operation is increased by the presence of heart disease. The statistics are too limited for this risk to be expressed more precisely. The heart in the elderly is no longer a normal heart. The myocardial functional reserve declines, the quality of the A.V. conduction is not always good and vascular fibrosis progresses. Surgical operation thus increases the risk of a cardio-vascular accident. One should distinguish the risk due simply to old age. The existence of known heart disease often leads to heart failure which is difficult to treat. The great risk of surgical operation is then the risk of overloading the heart. In the absence of known heart disease, one should beware of latent coronary insufficiency. The major risk is then hypoxia. The special problem of degenerative A.V. conduction disorders may require the insertion of a pace-maker. Pre-opératoire cardio-vascular assessment is thus necessary in the elderly subject. It should, however, remain simple. Careful history and auscultation, verification of the periphéral arteries, chest XRay and E.C.G.

Adaptation, Physiological↗

Free amino acid analysis of guinea pig perilymph: a possible clinical assay for the PLF enigma?

Controversy prevails regarding the accuracy of the clinical diagnosis of perilymphatic fistula (PLF). The diagnosis of PLF has been based on the subjective evaluation of vestibular function tests and the intraoperative macroscopic visualization of "clear fluid" from the oval/round windows at the time of exploratory tympanotomy. However, the subjective visual characterization of PLF varies among observing surgeons. Furthermore, perilymph can be "contaminated" with serum, blood, cerebrospinal fluid (CSF), and local anesthesia. This article presents a scientific biochemical microassay for the free amino acid profile of perilymph. Microaliquots of uncontaminated perilymph were sampled from the bilateral round windows (scala tympani) of 20 guinea pigs and analyzed for 19 free amino acid concentrations (FAAC) by high-performance liquid chromatography (HPLC). These samples were compared with the FAAC of guinea pig serum samples. Perfect predictor value ranges were nonoverlapping for 12 of 19 free amino acids in perilymph vs. plasma. Amino acid microassay of middle ear fluid for verification of "true" perilymph vs. nonperilymph fluids by the identification of nonoverlapping FAA markers may allow scientific verification of the existence of PLF in "suspected" patients.

Amino Acids↗

[The dynamics of clinical and functional condition of patients with different variants of coronary heart disease course during the period of long-term outpatient follow-up].

With the purpose to study clinical and functional parameters of coronary heart disease (CHD) course, the authors carried out a complex examination of 376 patients (308 men and 68 women). The evolution of their psychophysiological condition was evaluated after 1, 3, 5, and 7 years. 3 variants of disease course were distinguished: 1--clinical remission--was observed in 27 (7.1%) patients; 2--stable CHD course--in 263 (69.9%) patients; 3--complicated CHD course--in 86 (23%) patients. The complicated disease course was characterized by increasing clinical manifestations of angina with myocardial contractility impairment, shorter remission periods, low activity tolerance, and persistent hypercholesterinemia. These patients had persistent hypochondric and depressive manifestations of psychoemotional disadaptation, which confirms the interrelation between the disease and psychosomatic disturbances. Regression analysis proved high informative value of a range of clinical parameters, which allow verification of diagnostical process during long-term follow-up, and improvement of treatment quality.

Adaptation, Psychological↗

Automated melanoma detection: multispectral imaging and neural network approach for classification.

Our aim in the present research is to investigate the diagnostic performance of artificial neural networks (ANNs) applied to multispectral images of cutaneous pigmented skin lesions as well as to compare this approach to a standard traditional linear classification method, such as discriminant function analysis. This study involves a series of 534 patients with 573 cutaneous pigmented lesions (132 melanomas and 441 nonmelanoma lesions). Each lesion was analyzed by a telespectrophotometric system (TS) in vivo, before surgery. The system is able to acquire a set of 17 images at selected wavelengths from 400 to 1040 nm. For each wavelength, five lesion descriptors were extracted, related to the criteria of the ABCD (for asymmetry, border, color, and dimension) clinical guide for melanoma diagnosis. These variables were first reduced in dimension by the use of factor analysis techniques and then used as input data in an ANN. Multivariate discriminant analysis (MDA) was also performed on the same dataset. The whole dataset was split into two independent groups: i.e., train (the first 400 cases, 95 melanomas) and verification set (last 173 cases, 37 melanomas). Factor analysis was able to summarize the data structure into ten variables, accounting for at least 90% of the original parameters variance. After proper training, the ANN was able to classify the population with 80% sensitivity, 72% specificity, and 78% sensitivity, 76% specificity for the train and validation set, respectively. Following ROC analysis, area under curve (AUC) was 0.852 (train) and 0.847 (verify). Sensitivity and specificity values obtained by the standard discriminant analysis classifier resulted in a figure of 80% sensitivity, 60% specificity and 76% sensitivity, 57% specificity for the train and validation set, respectively. AUC for MDA was 0.810 and 0.764 for the train and verify set, respectively. Classification results were significantly different between the two methods both for diagnostic scores and model stability, which was worse for MDA.

Adolescent↗

Low-frequency velocity correlation spectrum of fluid in a porous media by modulated gradient spin echo.

In addition to the fast correlation for local stochastic motion, the molecular velocity correlation function in a fluid enclosed within the pore boundaries features a slow long time-tail decay. Here we present its study by the NMR modulated gradient spin-echo method (MGSE) [1] on a system of water trapped in the space between the closely packed polystyrene beads. With MGSE pulse sequence, a repetitive train of RF pulses with interspersed gradient pulses periodically modulates the spin phase. It gives the spin echo attenuation proportional to a value of the molecular velocity correlation spectrum at the modulation frequency. Covering the frequency range between Hz and MHz, it is a complement to the quasi-elastic neutron scattering, and so a suitable technique for the investigation of low frequency molecular dynamics in fluids. In our experiment, it enables to extract the low frequency correlation spectrum of water molecules confined in porous media. The function exhibits a negative long time-tail characteristic (a low frequency decay of the spectrum), which can be interpreted as a molecular back scattering on boundaries. The results can be well fitted with the spectrum calculated from the solution of the Langevin equation for restricted diffusion (which exhibits an exponential decay) [2] as well as with the spectrum obtained when simulating the hydrodynamics of molecular motion constrained by capillary walls (which gives an algebraic decay) [3]. Despite much work on theories and simulation, which predict slow negative long time tail of molecular velocity correlation dynamics in confined fluids, the obtained velocity correlation spectrum is the first experimental evidence to confirm these effects. The obtained dependence of spin echo attenuation on time, gradient strength and modulation frequency is also the first experimental verification of the recently developed approach to the spin echo in porous media, that uses the spin phase average with the cumulant expansion to get the attenuation as a discord of spin spatial coherence [4].

Magnetic Resonance Spectroscopy↗