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Development of a single mode electromagnetic resonant cavity for rewarming of cryopreserved biomaterials.

An electromagnetic (EM) heating system is developed to achieve the rapid and uniform warming of cryopreserved biomaterials. Using the heating system, a rectangular resonant cavity is excited in TE101 mode at frequencies near 434 MHz. In experiments, a spherical phantom of biomaterial with a diameter of 36 mm is placed at the center of the cavity. The phantom is first cooled down to about -80 degrees C within the cavity and then thawed by EM absorption. Results show that EM warming can produce much higher warming rate than conventional water-bath warming method. The spatial temperature distribution in the phantom during EM warming is also more uniform than that during the water-bath warming.

Adhesives↗

LSimpute: accurate estimation of missing values in microarray data with least squares methods.

Microarray experiments generate data sets with information on the expression levels of thousands of genes in a set of biological samples. Unfortunately, such experiments often produce multiple missing expression values, normally due to various experimental problems. As many algorithms for gene expression analysis require a complete data matrix as input, the missing values have to be estimated in order to analyze the available data. Alternatively, genes and arrays can be removed until no missing values remain. However, for genes or arrays with only a small number of missing values, it is desirable to impute those values. For the subsequent analysis to be as informative as possible, it is essential that the estimates for the missing gene expression values are accurate. A small amount of badly estimated missing values in the data might be enough for clustering methods, such as hierachical clustering or K-means clustering, to produce misleading results. Thus, accurate methods for missing value estimation are needed. We present novel methods for estimation of missing values in microarray data sets that are based on the least squares principle, and that utilize correlations between both genes and arrays. For this set of methods, we use the common reference name LSimpute. We compare the estimation accuracy of our methods with the widely used KNNimpute on three complete data matrices from public data sets by randomly knocking out data (labeling as missing). From these tests, we conclude that our LSimpute methods produce estimates that consistently are more accurate than those obtained using KNNimpute. Additionally, we examine a more classic approach to missing value estimation based on expectation maximization (EM). We refer to our EM implementations as EMimpute, and the estimate errors using the EMimpute methods are compared with those our novel methods produce. The results indicate that on average, the estimates from our best performing LSimpute method are at least as accurate as those from the best EMimpute algorithm.

Algorithms↗

Anatomical-based FDG-PET reconstruction for the detection of hypo-metabolic regions in epilepsy.

Positron emission tomography (PET) of the cerebral glucose metabolism has shown to be useful in the presurgical evaluation of patients with epilepsy. Between seizures, PET images using fluorodeoxyglucose (FDG) show a decreased glucose metabolism in areas of the gray matter (GM) tissue that are associated with the epileptogenic region. However, detection of subtle hypo-metabolic regions is limited by noise in the projection data and the relatively small thickness of the GM tissue compared to the spatial resolution of the PET system. Therefore, we present an iterative maximum-a-posteriori based reconstruction algorithm, dedicated to the detection of hypo-metabolic regions in FDG-PET images of the brain of epilepsy patients. Anatomical information, derived from magnetic resonance imaging data, and pathophysiological knowledge was included in the reconstruction algorithm. Two Monte Carlo based brain software phantom experiments were used to examine the performance of the algorithm. In the first experiment, we used perfect, and in the second, imperfect anatomical knowledge during the reconstruction process. In both experiments, we measured signal-to-noise ratio (SNR), root mean squared (rms) bias and rms standard deviation. For both experiments, bias was reduced at matched noise levels, when compared to post-smoothed maximum-likelihood expectation-maximization (ML-EM) and maximum a posteriori reconstruction without anatomical priors. The SNR was similar to that of ML-EM with optimal post-smoothing, although the parameters of the prior distributions were not optimized. We can conclude that the use of anatomical information combined with prior information about the underlying pathology is very promising for the detection of subtle hypo-metabolic regions in the brain of patients with epilepsy.

Algorithms↗

Double-tilt electron tomography.

Fidelity of tomographic reconstructions is improved and reconstruction artifacts are reduced, without increasing the number of projections, by combining tilt series taken around two orthogonal axes. Test reconstructions were made from high-voltage EM of rat liver mitochondria in a 0.6 micron thick plastic section. A number of schemes for selecting tilt angles for the projections are compared. A new method for aligning fiducial markers is described. It uses an iterative algorithm to determine the shift, scale, in-plane rotation and tilt angle for each tilt image, enforcing agreement of the expected locations of the fiducial markers in 3D space. These 3D locations are used to find the orientation between two tilt series and to merge both sets of projections.

Animals↗

Frequency-sensitive competitive learning for scalable balanced clustering on high-dimensional hyperspheres.

Competitive learning mechanisms for clustering, in general, suffer from poor performance for very high-dimensional (>1000) data because of "curse of dimensionality" effects. In applications such as document clustering, it is customary to normalize the high-dimensional input vectors to unit length, and it is sometimes also desirable to obtain balanced clusters, i.e., clusters of comparable sizes. The spherical kmeans (spkmeans) algorithm, which normalizes the cluster centers as well as the inputs, has been successfully used to cluster normalized text documents in 2000+ dimensional space. Unfortunately, like regular kmeans and its soft expectation-maximization-based version, spkmeans tends to generate extremely imbalanced clusters in high-dimensional spaces when the desired number of clusters is large (tens or more). This paper first shows that the spkmeans algorithm can be derived from a certain maximum likelihood formulation using a mixture of von Mises-Fisher distributions as the generative model, and in fact, it can be considered as a batch-mode version of (normalized) competitive learning. The proposed generative model is then adapted in a principled way to yield three frequency-sensitive competitive learning variants that are applicable to static data and produced high-quality and well-balanced clusters for high-dimensional data. Like kmeans, each iteration is linear in the number of data points and in the number of clusters for all the three algorithms. A frequency-sensitive algorithm to cluster streaming data is also proposed. Experimental results on clustering of high-dimensional text data sets are provided to show the effectiveness and applicability of the proposed techniques. Index Terms-Balanced clustering, expectation maximization (EM), frequency-sensitive competitive learning (FSCL), high-dimensional clustering, kmeans, normalized data, scalable clustering, streaming data, text clustering.

Artificial Intelligence↗

In-vivo and in-vitro dextromethorphan metabolism in SD and DA rat. An animal model of the debrisoquine-type polymorphic oxidation in man.

The female dark Agouti (DA) rat is well established as an animal model for the debrisoquine poor metabolizer phenotype (PM), whereas the SD rat represents the extensive metabolizer (EM). It is not known, however, if the DA rat also is representative for the dextromethorphan (DEM) PM, a compound recently demonstrated to be subjected to the debrisoquine phenotype in man. Studies were performed, therefore, to evaluate in-vivo and in-vitro metabolism of DEM in DA and SD rats. After oral administration of 50 mg/kg of DEM, the DA rat excreted 25 +/- 6% of the dose in 72-hr urine as O-demethylated product (dextrorphan), whereas the SD excreted 40 +/- 9% (P less than 0.002). Metabolic ratio of O-demethylation was 0.46 +/- 0.11 in DA and 0.02 +/- 0.01 in SD (P less than 0.001). As a compensatory mechanism, N-demethylation was ninefold increased in DA compared to SD (8.0 +/- 3% of the dose excreted in urine of DA as methoxymorphinan vs 0.9 +/- 0.7% in SD) (P less than 0.001). Total plasma clearance of DEM was 95 +/- 20 ml/min/kg in SD and 45 +/- 13 ml/min/kg in DA (P less than 0.001). In vitro, microsomal affinity for DEM O-demethylation was greater than 50 times higher in SD than in DA rats (P less than 0.004), whereas Vmax did not differ statistically. Vmax for N-demethylation was 80% increased in DA (P less than 0.01), whereas corresponding Km values did not differ. It appears that the differences in DEM metabolism between DA and SD rats are qualitatively similar to human EM and PM phenotypes, respectively. Whether this is also true for the underlying mechanism(s) however, remains to be resolved.

Algorithms↗

Inverse problem solution techniques as applied to indirect in situ estimation of fish target strength.

In situ indirect methods of fish target strength (TS) estimation are analyzed in terms of the inverse techniques recently applied to the problem in question. The solution of this problem requires finding the unknown probability density function (pdf) of fish target strength from acoustic echoes, which can be estimated by solving the integral equation, relating pdf's of echo variable, target strength, and beam pattern of the echosounder transducer. In the first part of the paper the review of existing indirect in situ TS-estimation methods is presented. The second part introduces the novel TS-estimation methods, viz.: Expectation, Maximization, and Smoothing (EMS), Windowed Singular Value Decomposition (WSVD), Regularization and Wavelet Decomposition, which are compared using simulations as well as actual data from acoustic surveys. The survey data, acquired by the dual-beam digital echosounder, were thoroughly analyzed by numerical algorithms and the target strength and acoustical backscattering length pdf's estimates were calculated from fish echoes received in the narrow beam channel of the echosounder. Simultaneously, the estimates obtained directly from the dual-beam system were used as a reference for comparison of the estimates calculated by the newly introduced inverse techniques. The TS estimates analyzed in the paper are superior to those obtained from deconvolution or other conventional techniques, as the newly introduced methods partly avoid the problem of ill-conditioned equations and matrix inversion.

Acoustics↗

Metabolism of ethyl methyl sulphide and sulphoxide in rat microsomal fractions.

1. Gas chromatographic (GC) methods for the analysis of ethyl methyl sulphide (EMS) and its corresponding sulphoxide (EMSO) and sulphone (EMSO2) in rat microsomes and aspects of the in vitro metabolism of EMS and EMSO are described. 2. EMS and the internal standard (dimethyl sulphide) were extracted by a headspace procedure and separated satisfactorily using a column packed with 4% Carbowax 20 M/0.8% KOH on Carbopack B. EMSO, EMSO2 and the internal standard n-propyl sulphone were separated satisfactorily using a 2-m column packed with 10% Carbowax 20 M on Chromosorb W. 3. Under the optimum conditions (incubation of 10 min and microsomal protein content of approximately 4 mg/ml), 10% of the initial EMS concentration (2.5 mM) was converted to the corresponding sulphoxide in rat liver microsomal incubations. However, < 0.1% of the sulphone was detected when rat liver microsomes were incubated with EMS. Similarly, 2.5% of the initial EMSO concentration (2.5 mM) was converted to the corresponding sulphone by rat liver microsomes (approximately 4 mg/ml protein) during an incubation of 30 min. However, no EMS was detected after incubation with EMSO under these conditions. 4. The estimated apparent Vmax and Km for the sulphoxidation of EMS were 3.8+/-0.02 nmol/mg protein/min and 1.9+/-0.10 mM respectively. Vmax1, Vmax2 and Km1 and Km2 for the S-oxidation of EMSO were 0.5+/-0.01 and 0.2+/-0.01 nmol/mg protein/min and 0.7+/-0.02 and 0.1+/-0.00 mM respectively. 5. Studies with selective inducers and inhibitors of microsomal monooxygenases indicated that the sulphoxidation of EMS is mediated mainly by FMO, whereas both FMO and cytochrome P450 are involved in the S-oxidation of EMSO.

Algorithms↗

EMS defibrillation-first policy may not improve outcome in out-of-hospital cardiac arrest.

OBJECTIVE: Early defibrillation using automated external defibrillators (AEDs) has been advocated to improve survival in witnessed out-of-hospital cardiac arrest (OHCA) due to pulseless ventricular tachycardia (VT) and ventricular fibrillation (VF). However, when VT/VF is untreated and prolonged for more than a few minutes, defibrillation using AEDs may fail. METHODS: This retrospective study reviewed the charts from local emergency medical service (EMS) between the years 1993 to 2001 to evaluate the value of the AED after its introduction into our EMS. All witnessed OHCA due to VT/VF were analysed; cases of collapse witnessed by EMS were excluded. The primary endpoint was defined as survival to hospital discharge and at 1-year follow-up, and the secondary endpoint as survival without major neurological deficit. A total of 76 patients were treated for witnessed VT/VF before the implementation of the AED and 92 patients after its implementation. RESULTS: Before the introduction of paramedic AED defibrillation, physician defibrillation was performed at 15.6 min (+/-5.5, S.D.). After the introduction of AED defibrillation, paramedic defibrillation was performed at 5.7 min (+/-2.4, S.D.); the mean response interval from the call to defibrillation was shortened significantly (P<0.001). At the same time, survival to hospital discharge decreased from 23.7% (18/76 patients) to 14.1% (13/92) (P=0.112) and at 1-year follow-up from 17.1% (13/76) to 9.8% (9/92) (P=0.161). Favourable neurological outcome at 1-year follow-up also decreased from 14.5% (11/76) to 8.7% (8/92) (P=0.239). CONCLUSION: Implementation of the AED did not improve survival or a favourable neurological outcome in patients with OHCA due to VF/VT. However, with 5.7 min time to defibrillation, our EMS did not meet the criteria for early defibrillation. For prolonged periods of VT/VF, initial basic life support (BLS) may be superior to immediate AED. If response times of <4 min cannot be attained by the emergency systems, reconsidering of resuscitation algorithms seems to be advisable.

Algorithms↗

Patients with chest pain calling 9-1-1 or self-transporting to reach definitive care: which mode is quicker?

OBJECTIVE: We examined differences in transport times for patients with chest pain who used private transportation compared with patients who used emergency medical services (EMS) to reach definitive medical care. METHODS: This was a retrospective cohort study with data used from the Rapid Early Action for Coronary Treatment (REACT) trial conducted in 20 US cities. Elapsed time to care was examined through the use of (1) decision to seek care to initial care (emergency department [ED] arrival versus EMS arrival on scene [n=1209]); (2) decision to ED arrival (for both groups [n=2388]); (3) time to thrombolytic therapy once admitted to the ED (for both groups [n=309]); and (4) decision to seek care to thrombolytic therapy (n=276). Elapsed travel times were ranked within Zip Codes and submitted to a nested analysis of variance model to determine if elapsed times were different between modes of transport. RESULTS: Private transportation (35 minutes) resulted in faster ED arrival than using EMS (39 minutes, P =.0014). However, if one considers EMS treatment to be initial care, calling 9-1-1 (6 minutes) resulted in much quicker care than patients using private transportation to the ED (32 minutes, P <.001). Transport by EMS resulted in a shorter elapsed time to thrombolytic administration compared with patients using private transportation when considering ED "door-to-needle" time (32 vs 49 minutes, respectively [P <.001]) or time from decision to seek care until administration of thrombolytic therapy (75 vs 92 minutes, respectively, [P =.042]). CONCLUSIONS: Although private transportation results in a faster trip to the ED, quicker care is obtained with the use of EMS.

Adult↗

Effect of grain colour gene (R) on grain dormancy and sensitivity of the embryo to abscisic acid (ABA) in wheat.

The level of grain dormancy and sensitivity to ABA of the embryo, a key factor in grain dormancy, were examined in developing grains of a white-grained wheat line, Novosibirskaya 67 (NS-67), and its red-grained near-isogenic lines (ANK-1A to -1D); a red-grained line, AUS 1490, and its white-grained mutant line (EMS-AUS). ANK lines showed higher levels of grain dormancy than NS-67 at harvest maturity. AUS 1490 grain also showed higher dormancy than EMS-AUS grain. These results suggest that the R gene for grain colour can enhance grain dormancy. However, the dormancy effect conferred by the R gene was not large, suggesting that it plays a minor role in the development of grain dormancy. Water extracts of AUS 1490 and EMS-AUS bran contained germination inhibitors equivalent to 1-10 microM ABA, although there was no difference in the amount of inhibitors between AUS 1490 and EMS-AUS. Thus, the grain colour gene of AUS 1490 did not appear to enhance the level of grain dormancy by accumulating germination inhibitors in its bran. Sensitivity to ABA of embryos was higher in grains collected around harvest-maturity for ANK lines and AUS 1490, compared with NS-67 and EMS-AUS. The R gene might enhance grain dormancy by increasing the sensitivity of embryos to ABA.

Abscisic Acid↗

Dehydration behavior of eprosartan mesylate dihydrate.

Eprosartan mesylate (SKF 108566-J; EM) is an antihypertensive agent approved for marketing in the USA. EM dihydrate was prepared by three methods, one of which included suspending the anhydrous drug in an aqueous solution of 1.0 M methanesulfonic acid to form a slurry, followed by filtration. The dehydration kinetics of EM dihydrate were derived by analyzing the fit of the isothermal thermogravimetric analytical (TGA) data to numerous kinetic models. EM dihydrate undergoes dehydration in two distinct steps, each involving the loss of 1 mol of water at 25-70 degrees C and 70-120 degrees C, respectively. Recrystallization of EM occurs at approximately 120-140 degrees C after dehydration to the anhydrous phase. This explanation is supported by variable temperature powder X-ray diffractometry. The mechanism of the dehydration reaction is complex, the dependence of the reaction rate on temperature varying as a function of the particles size. For the dihydrate of sieve fraction <125 microm, the kinetics of the first and second dehydration steps are consistent with the Avrami-Erofeev equation (A3, n = 1/3) over the temperature range studied, corresponding to three-dimensional growth of nuclei. In contrast, for the 125-180-microm and 180-250-microm sieve fractions, the kinetics are best described by the two-dimensional phase boundary reaction (R2) at a lower dehydration temperature (i.e., 28.3 degrees C), and by the Avrami-Erofeev equation (A3, n = 1/3) at a higher dehydration temperature (i.e., 93.7 degrees C). The activation energies (15-40 kcal/mol) and frequency factors of the dehydration of EM dihydrate were determined both by Arrhenius plots of the isothermal rates determined by TGA and by Kissinger plots of the nonisothermal differential scanning calorimetric data. Hot stage microscopy of single crystals of EM dihydrate showed random nucleation at the surface and dehydration with the growth of microcrystals along the needle a axis. Cerius(2) molecular modeling software showed the existence of water channels along the a axis and enabled the observed dehydration behavior of EM dihydrate crystals to be explained in terms of the bonding environment of water molecules in the crystal structure.

Acrylates↗

A Numerical Implementation of Kolmogorov's Superpositions.

Hecht-Nielsen proposed a feedforward neural network based on Kolmogorov's superpositionsf(x(i), em leader,x(n))= summation operator q=02piPhi(q)(y(q)) that apply to all real valued continuous functions f(x(1), em leader, x(n)) defined on a Euclidean unit cube of dimension n >/= 2. This network has a hidden layer that is independent of f and that transforms the n-tuples (x(1), em leader, x(n)) into the 2n + 1 variables y(q), and an output layer in which f is computed. Kůrková has shown that such a network has an approximate implementation with arbitrary activation functions of sigmoidal type. Actual implementation is, however, impeded by the lack of numerical algorithms for the hidden layer which contain continuous functions of the formy(q)=Sigma(n)(p=1)alpha(p)psi(x(p)+qa) with constants a and alpha(p). This paper gives an explicit numerical implementation of the hidden layer that also enables the implementation of the output layer. Copyright 1996 Elsevier Science Ltd

Journal Article↗

Localization accuracy in single-molecule microscopy.

One of the most basic questions in single-molecule microscopy concerns the accuracy with which the location of a single molecule can be determined. Using the Fisher information matrix it is shown that the limit of the localization accuracy for a single molecule is given by, lambda(em)/2pi n(a) square root of gammaAt, where lambda(em), n(a), gamma, A, and t denote the emission wavelength of the single molecule, the numerical aperture of the objective, the efficiency of the optical system, the emission rate of the single molecule and the acquisition time, respectively. Using Monte Carlo simulations it is shown that estimation algorithms can come close to attaining the limit given in the expression. Explicit quantitative results are also provided to show how the limit of the localization accuracy is reduced by factors such as pixelation of the detector and noise sources in the detection system. The results demonstrate what is achievable by single-molecule microscopy and provide guidelines for experimental design.

Biopolymers↗

Electromagnetic interference from a muscle stimulation device causing discharge of an implantable cardioverter defibrillator: epicardial bipolar and endocardial bipolar sensing circuits are compared.

This case report is about two patients with two different types of ICDs who underwent electrical muscle stimulation (EMS) therapy. In one patient with an ICD that has epicardial screw-in bipolar sensing leads, electromagnetic interference (EMI) from the EMS device caused the delivery of an inappropriate ICD discharge. In a second patient with an ICD with endocardial true bipolar sensing, there was no evidence of EMI during the EMS therapy despite all of our attempts to reproduce it. The sensing circuits in the two different ICDs are compared.

Aged↗

Medical textbook summarization and guided navigation using statistical sentence extraction.

We present a method for automated medical textbook and encyclopedia summarization. Using statistical sentence extraction and semantic relationships, we extract sentences from text returned as part of an existing textbook search (similar to a book index). Our system guides users to the information they desire by summarizing the content of each relevant chapter or section returned in the search. The summary is tailored to contain sentences that specifically address the user's search terms. Our clustering method selects sentences that contain concepts specifically addressing the context of the query term in each of the returned sections. Our method examines conceptual relationships from the UMLS and selects clusters of concepts using Expectation Maximization (EM). Sentences associated with the concept clusters are shown to the user. We evaluated whether our extracted summary provides a suitable answer to the user's question.

Abstracting and Indexing↗

Magnetic resonance imaging-guided attenuation and scatter corrections in three-dimensional brain positron emission tomography.

Reliable attenuation correction represents an essential component of the long chain of modules required for the reconstruction of artifact-free, quantitative brain positron emission tomography (PET) images. In this work we demonstrate the proof of principle of segmented magnetic resonance imaging (MRI)-guided attenuation and scatter corrections in three-dimensional (3D) brain PET. We have developed a method for attenuation correction based on registered T1-weighted MRI, eliminating the need of an additional transmission (TX) scan. The MR images were realigned to preliminary reconstructions of PET data using an automatic algorithm and then segmented by means of a fuzzy clustering technique which identifies tissues of significantly different density and composition. The voxels belonging to different regions were classified into air, skull, brain tissue and nasal sinuses. These voxels were then assigned theoretical tissue-dependent attenuation coefficients as reported in the ICRU 44 report followed by Gaussian smoothing and addition of a good statistics bed image. The MRI-derived attenuation map was then forward projected to generate attenuation correction factors (ACFs) to be used for correcting the emission (EM) data. The method was evaluated and validated on 10 patient data where TX and MRI brain images were available. Qualitative and quantitative assessment of differences between TX-guided and segmented MRI-guided 3D reconstructions were performed by visual assessment and by estimating parameters of clinical interest. The results indicated a small but noticeable improvement in image quality as a consequence of the reduction of noise propagation from TX into EM data. Considering the difficulties associated with preinjection TX-based attenuation correction and the limitations of current calculated attenuation correction, MRI-based attenuation correction in 3D brain PET would likely be the method of choice for the foreseeable future as a second best approach in a busy nuclear medicine center and could be applied to other functional brain imaging modalities such as SPECT.

Algorithms↗

Automated external defibrillators: to what extent does the algorithm delay CPR?

STUDY OBJECTIVE: Maximizing cardiopulmonary resuscitation (CPR) during resuscitation may improve survival. Resuscitation protocols stack up to 3 shocks to achieve defibrillation, followed by an immediate postdefibrillation pulse check. The purpose of this study is to evaluate outcomes of rhythm reanalyses immediately after shock, stacked shocks, and initial postshock pulse checks in relation to achieving a pulse and initiating CPR. METHODS: We conducted an observational study of patients with ventricular fibrillation treated by first-tier emergency medical services (EMS). We collected data from EMS, dispatch, and hospital records. Additionally, we analyzed automatic external defibrillator recordings to determine the proportion of cardiac arrest victims who were defibrillated and achieved a pulse according to shock number (single versus stacked shock), proportion of victims with a pulse during the initial postdefibrillation pulse check, and interval from initial shock to CPR. RESULTS: The study included 481 cardiac arrest subjects. Automatic external defibrillators terminated ventricular fibrillation with the initial shock in 83.6% (n=402) of cases. A second shock terminated ventricular fibrillation in an additional 7.5% (n=36) of cases, and a third shock terminated ventricular fibrillation in 4.8% (n=23) of cases. The initial sequence of 3 shocks failed to terminate ventricular fibrillation in 4.1% (n=20) of cases. In total, automatic external defibrillators performed 560 rhythm reanalyses during the initial shock sequence and delivered 122 "stacked" shocks. Termination of ventricular fibrillation was not synonymous with return of a pulse. The initial shock produced a pulse that was eventually detected in 21.8% (105/481) of cases. Stacked shocks produced a pulse in 10.7% (13/122) of cases. For the 24.5 % (n=118) of cases in which a pulse returned, the pulse was detected during the initial postshock pulse check only 12 times, or 2.5% of all cases. The median interval from initial shock until CPR was 29 (23,41) seconds. CONCLUSION: Rhythm reanalyses, stacked shocks, and postshock pulse checks had low yield for achieving or detecting return of a pulse. CPR was not initiated until 29 seconds after the initial shock.

Aged↗