Nedocromil sodium (NS- Tilade) is an effective therapeutic agent against asthma and has been shown to exhibit antiinflammatory activity in vitro. The aim of this study was to assess the effect of NS on the serum neutrophil (NCA) and eosinophil (ECA) chemotactic activity and mononuclear cells-derived histamine releasing factor (HRF) activity in 14 patients with seasonal allergic asthma. The chemotactic activities, HRF and bronchial reactivity to histamine (PC20H in mg/ml) were determined before the grass-pollen season and at the end of the 14-day placebo treatment and 21-day NS treatment during the pollen-season. NCA and ECA were assessed using of the Boyden chamber methods. Blood samples for mononuclear cells culture were collected during the trial. The supernatants were assayed for HRF activity with basophils from a single donor. The NCA index was unaltered during the trial. There was a significant (p < 0.05) increase in the ECA after the NS treatment period (ECA index--2.5) compared with out of season and after placebo treatment (ECA index, 1.88 and 1.82). HRF activity increased after placebo compared with out of season (HRF % activity--38.62 before season, 47.61 after placebo p < 0.05) but NS did not revealed the further effect on HRF activity (49.81 p>> 0.05). During placebo the significant decrease in PC20H from 1.81 mg/ml to 0.54 mg/ml (p < 0.05) was observed. NS did not have the effect on nonspecific bronchial reactivity--PC20H--0.74 mg/ml (p>> 0.05). The correlation between PC20H and spontaneous production of HRF activity was not found. The results indicate that NS has some effect on inflammatory process which takes place in seasonal asthmatic patients during the natural allergic exposure.

OBJECTIVE

To obtain the recombinant IgE-dependent histamine-releasing factors of Schistosoma japonicum and Clonorchis sinensis (rSjHRF and rCsHRF) and to study the effect of recombinant HRFs to induce histamine release from sensitized rat mast cells.

METHODS

The complete coding regions of SjHRF and CsHRF were cloned separately, and the recombinant plasmids were respectively transformed and expressed in BL21 cells. The soluble recombinant rSjHRF and rCsHRF were purified. Aliquots of the mast cells obtained from the lungs of OVA-immunized rats were separately incubated with rSjHRF and rCsHRF and the released histamine was measured by the OPT spectrofluorometric procedure. The dose-dependent curves and the kinetics of histamine release induced by rSjHRF and rCsHRF were prepared.

RESULTS

The recombinant plasmids pET-30-rSjHRF and pET-30-rCsHRF were constructed successfully and the purified soluble recombinant proteins rSjHRF and rCsHRF were obtained by affinity chromatography. rSjHRF and rCsHRF induced histamine release from sensitized mast cells in a dose-dependent manner. At the concentration of 150 mg/L, the average rate of histamine release from sensitized mast cells induced by rSjHRF and rCsHRF were 49.78% and 32.63%, respectively. Histamine release increased with prolonged reaction time and the maximal release occurred at 35 min.

CONCLUSIONS

The recombinant parasite-originated IgE-dependent HRFs show an effect of inducing histamine release from sensitized mast cells, suggesting that this protein would play a role in type I hypersensitivity in hosts with parasitic infections.

OBJECTIVE

To evaluate visual field loss using multifocal ERG(m-ERG), multifocal VEP(m-VEP), and Heidelberg Retina Flowmeter(HRF) in a patient with branch retinal artery occlusion(BRAO) and brain infarction.

METHODS

A 38-year-old man noticed inferior-nasal visual field loss in the left eye, and was referred to Keio University Hospital. He suffered from paralysis in the left leg due to brain infarction at the age of 24. However, he had not noticed visual field loss due to the brain infarction. His left fundus showed retinal edema in the area of a superior-temporal retinal artery occulusion. He was diagnosed as having BRAO. The Goldmann and Humphry perimetric examinations revealed homonymous quadrantanopia in the upper left field as well as inferior visual field defect in the left eye.

RESULTS

Both m-ERG and m-VEP, especially second-kernel responses, were reduced in the affected retinal area of BRAO. But only m-VEP was affected in the corresponding area of homonymous quadrantanopia in the upper left field. The retinal flow in the area with BRAO evaluated by HRF was decreased in some areas and not in others, suggesting that retinal function was not necessarily consistent with retinal circulation.

CONCLUSIONS

m-ERG and m-VEP are useful To differentiate retinal lesions from brain lesions in visual field loss.

The exploration of retinal vessel structure is colossally important on account of numerous diseases including stroke, Diabetic Retinopathy (DR) and coronary heart diseases, which can damage the retinal vessel structure. The retinal vascular network is very hard to be extracted due to its spreading and diminishing geometry and contrast variation in an image. The proposed technique consists of unique parallel processes for denoising and extraction of blood vessels in retinal images. In the preprocessing section, an adaptive histogram equalization enhances dissimilarity between the vessels and the background and morphological top-hat filters are employed to eliminate macula and optic disc, etc. To remove local noise, the difference of images is computed from the top-hat filtered image and the high-boost filtered image. Frangi filter is applied at multi scale for the enhancement of vessels possessing diverse widths. Segmentation is performed by using improved Otsu thresholding on the high-boost filtered image and Frangi's enhanced image, separately. In the postprocessing steps, a Vessel Location Map (VLM) is extracted by using raster to vector transformation. Postprocessing steps are employed in a novel way to reject misclassified vessel pixels. The final segmented image is obtained by using pixel-by-pixel AND operation between VLM and Frangi output image. The method has been rigorously analyzed on the STARE, DRIVE and HRF datasets.

Automatic classification of glaucoma from fundus images is a vital diagnostic tool for Computer-Aided Diagnosis System (CAD). In this work, a novel fused feature extraction technique and ensemble classifier fusion is proposed for diagnosis of glaucoma. The proposed method comprises of three stages. Initially, the fundus images are subjected to preprocessing followed by feature extraction and feature fusion by Intra-Class and Extra-Class Discriminative Correlation Analysis (IEDCA). The feature fusion approach eliminates between-class correlation while retaining sufficient Feature Dimension (FD) for Correlation Analysis (CA). The fused features are then fed to the classifiers namely Support Vector Machine (SVM), Random Forest (RF) and K-Nearest Neighbor (KNN) for classification individually. Finally, Classifier fusion is also designed which combines the decision of the ensemble of classifiers based on Consensus-based Combining Method (CCM). CCM based Classifier fusion adjusts the weights iteratively after comparing the outputs of all the classifiers. The proposed fusion classifier provides a better improvement in accuracy and convergence when compared to the individual algorithms. A classification accuracy of 99.2% is accomplished by the two-level hybrid fusion approach. The method is evaluated on the public datasets High Resolution Fundus (HRF) and DRIVE datasets with cross dataset validation.

Keywords: CCM; Classification; Correlation; Feature extraction; Glaucoma; IEDCA.

OBJECTIVE

To determine the interobserver reproducibility of Heidelberg retinal flowmeter (HRF) blood flow measurements using independently selected study areas for pixel-by-pixel analysis.

METHODS

Blood flow measurements were performed on 257 scans from 15 patients, 14 of whom had glaucoma or ocular hypertension. HRF was used to record capillary perfusion in a 2560x640 mum area of the supratemporal peripapillary region and pixel-by-pixel analysis was performed from an area adjacent to the optic disc with a minimum of 1600 pixels. Each observer independently selected the area for analysis. The percentage of pixels with <1 arbitrary unit of flow (no flow) and 10, 25, 50, 75, and 90th percentiles of flow values was calculated. Interobserver variability was assessed by estimating the intraclass correlation coefficient (ICC) and its 95% confidence interval. Bland-Altman plots of the difference between the 2 physicians versus the average of the 2 physicians for each outcome were created.

RESULTS

ICC was 0.79 (range: 0.74 to 0.83) for mean flow values. For 0, 10, 25, 50, 75, and 90th percentiles of flow, the ICC was 0.67 (0.60 to 0.73), 0.74 (0.68 to 0.79), 0.82 (0.78 to 0.86), 0.85 (0.82 to 0.88), 0.85 (0.81 to 0.88), and 0.77 (0.72 to 0.82), respectively. Zero flow pixels had a nonsignificant mean difference between observers (P=0.542), whereas the remainder of the flow values demonstrated significant mean differences.

CONCLUSIONS

This study demonstrates that independent observers can review high-quality HRF scans and may produce different absolute values while retaining strong consistency of agreement when independently selecting areas for analysis using the pixel-by-pixel method.

The Health Regulatory Focus Scale (HRFS) is a short scale which measures an individual's prevention and promotion focus in a health-specific context. The main objective of this study was to examine the psychometric properties of the newly translated German version of the HRFS. Reliability and item characteristics were found to be satisfactory. Validity of both subscales toward other psychological constructs including behavioral approach and avoidance, core self-evaluations, optimism, pessimism, neuroticism, as well as several measures of physical and mental health was shown. In addition, invariance of the measure across age and gender groups was shown. Exploratory as well as confirmatory factor analyses clearly indicated a two-factorial structure with a moderate correlation between the two latent constructs. Differences in health promotion and prevention focus between socio-demographic groups are discussed. The HRFS is found to be a valid and reliable instrument for the assessment of regulatory focus in health-related environments.

OBJECTIVE

To examine the influence of image alignment on the repeatability of blood flow measurements of the optic nerve.

METHODS

10 normal subjects were examined. Heidelberg retina tomograph imaging was performed to establish best location and focus for the temporal neuroretinal rim. Two high quality Heidelberg retina flowmeter (HRF) images were acquired for three methods of alignment: central, nasal, and temporal. A 10 x 10 pixel measurement window was selected and exactly reproduced on all images. The interquartile pixel values were used to calculate capillary flow. ANOVA, intraclass correlation coefficients (ICC) and the coefficient of repeatability (CoR) were used for analysis.

RESULTS

There was no difference between methods (p = 0.47) or between visits (p = 0.51). The ICCs were 0.83 for the central, 0.34 for the nasal, and 0.42 for the temporal alignment. The CoR was 31.5 for central (mean effect 235.1), 234.6 for nasal, and 256.7 for temporal alignment.

CONCLUSIONS

Central alignment was the most repeatable method for the measurement of neuroretinal rim capillary blood flow using the HRF.

Computer-based assessment of many cognitive processes (eg, anticipatory and response readiness processes) requires the use of invariant stimulus display times (SDT) and intertrial intervals (ITI). Although designs with invariant SDTs and ITIs have been used in functional magnetic resonance imaging (fMRI) research, such designs are problematic for fMRI studies because of collinearity issues. This study examined regressor modulation with trial-level reaction times (RT) as a method for improving signal detection in a go/no-go task with invariant SDTs and ITIs. The effects of modulating the go regressor were evaluated with respect to the detection of BOLD signal-change for the no-go condition. BOLD signal-change to no-go stimuli was examined when the go regressor was based on a (a) canonical hemodynamic response function (HRF), (b) RT-based amplitude-modulated (AM) HRF, and (c) RT-based amplitude and duration modulated (A&DM) HRF. Reaction time-based modulation reduced the collinearity between the go and no-go regressors, with A&DM producing the greatest reductions in correlations between the regressors, and greater reductions in the correlations between regressors were associated with longer mean RTs and greater RT variability. Reaction time-based modulation increased statistical power for detecting group-level no-go BOLD signal-change across a broad set of brain regions. The findings show the efficacy of using regressor modulation to increase power in detecting BOLD signal-change in fMRI studies in which circumstances dictate the use of temporally invariant stimulus presentations.

In this work, we employ simultaneous EEG-fMRI data acquired during a visually-guided attention task along with convolutional sparse coding (CSC) analysis to extract transient events from the EEG. Subsequently, we use these events in a standard voxel-wise fMRI analysis and compare the resultant activation maps with maps obtained using the subjects' response time (RT) in detection of visual target stimuli. We also employ FIR models to obtain HRF estimates using the detected CSC events. Our results show concordance between the resultant activation maps and consistent HRF shapes for most of the subjects, suggesting that CSC can be used as a tool for the detection of reliable events in the EEG.

A brief (<4 s) period of neural activation evokes a stereotypical sequence of vascular and metabolic events to create the hemodynamic response function (HRF) measured using functional magnetic resonance imaging (fMRI). Linear analysis of fMRI data requires that the HRF be treated as an impulse response, so the character and temporal stability of the HRF are critical issues. Here, a simple audiovisual stimulus combined with a fast-paced task was used to evoke a strong HRF across a majority, ∼77%, of cortex during a single scanning session. High spatiotemporal resolution (2-mm voxels, 1.25-s acquisition time) was used to focus HRF measurements specifically on the gray matter for whole brain. The majority of activated cortex responds with positive HRFs, while ∼27% responds with negative (inverted) HRFs. Spatial patterns of the HRF response amplitudes were found to be similar across subjects. Timing of the initial positive lobe of the HRF was relatively stable across the cortical surface with a mean of 6.1 ± 0.6 s across subjects, yet small but significant timing variations were also evident in specific regions of cortex. The results provide guidance for linear analysis of fMRI data. More importantly, this method provides a means to quantify neurovascular function across most of the brain, with potential clinical utility for the diagnosis of brain pathologies such as traumatic brain injury.

BACKGROUND

Prior studies comparing Hemodynamic Response Function (HRF) in the young and elderly adults based on fMRI data have reported inconsistent findings for brain vision and motor regions in healthy aging. It is shown that the averaging method employed in all previous works has caused this inconsistency. The averaging is so sensitive to outliers and noise. However, fMRI data are obscured with a major contribution of noise particularly in the elderly case.

METHODS

Deconvolution algorithm is here proposed for HRF extraction to achieve more robustness against noise. In spite of earlier works, proposed deconvolution algorithm yields compatible HRF results using either original or denoised fMRI data, though a large percentage of selected active voxels change in the latter case. In the current study, event-related fMRI data have been used for 18 subjects (8 young and 10 elderly adults) with a simple visual and motor task of pressing a key with index in response to the visual presentation of the word tap. Considering anatomically-defined vision and motor regions and preprocessing steps in FSL and SPM, the activated voxels have been selected according to t-test for which HRF is estimated using deconvolution method.

RESULTS

Experimental results demonstrate that HRF peak amplitudes do not differ significantly (P=0.8) in the vision region for the young and the elderly. In motor region, the HRF peak significantly increases for the young compared to the elderly (P<0.03). Repeating the procedure on the denoised fMRI data using MDL algorithm, the same results have been obtained.

CONCLUSIONS

In this study, a comparative study has been realized on the hemodynamic response properties associated with the young and the elderly adults on a simple visual and motor task.

Although the definitive source of the left hemisphere's superiority for visual word recognition remains illusive, some argue that the left (LH) and right (RH) hemispheres engage different strategies during early perceptual processes involved in stimulus encoding. In particular, it is proposed that the LH treats a word as a unitary perceptual group whereas the RH processes the letters comprising a word as a series of individual perceptual units. The present study investigated support for this processing distinction by examining hemispheric strategies for temporal integration using Prinzmetal and Millis-Wright's (1984) feature-binding paradigm. A total of 20 participants identified the colour and identity of a target letter, presented within a three-letter word (e.g., ART) or nonword (e.g., HRF), directed to their left or right visual field. Errors were classified on the basis of whether they involved substitution of a colour present within the stimulus but at a different location (ON error), or the substitution of a colour not present within the stimulus (OFF error). As anticipated, for word stimuli there was a higher proportion of OFF errors associated with trials directed to the RH, consistent with the notion that the LH treats words as single perceptual units and is hence biased toward miscombination of perceptual information present within the stimulus. The pattern of ON errors across stimulus type provided clear evidence of RH sequential encoding effects, with the number of errors increasing markedly across the ordinal position of the letters comprising the stimulus string. As such, these data provide new evidence that the LH's advantage for visual word recognition arises, at least in part, from the ability to encode verbal stimuli as single perceptual units.

The current study examined the hemodynamic timecourse of activation within a network of regions that is thought to be associated with visual imagery. Two experimental conditions were examined that were designed to place differential demands on specific nodes within the visual imagery network. The two tasks were an object inspection task and a mental rotation task. The two conditions recruited overlapping cortical regions; however several regions revealed a differential response to object inspection and mental rotation. The mental rotation condition elicited greater activation in parietal cortex, lateral occipital/temporal regions, and bilateral prefrontal cortex. Conversely, the object inspection condition elicited greater activation in inferior extrastriate cortex, the inferior frontal gyrus, and the right cerebellum. When examining the timecourse of activation three different timecourse patterns were observed across cortical regions and conditions. The shape of the hemodynamic timecourse appears to correspond strongly with the cognitive processing taking place within the region, not the stimulus paradigm. The paper discusses the significance of those varying timecourse shapes and has implications for the appropriateness of using the canonical hrf during fMRI data analysis.

Horizontal-Flow Roughing Filtration (HRF) is an alternative pretreatment method e.g. prior to Slow Sand Filtration (SSF). However, some of its limitations are that the effluent quality drops drastically at higher turbidity (>200NTU) and at higher filtration rate (>1 m h(-1)). To overcome these drawbacks, we suggested Direct Horizontal-Flow Roughing Filtration (DHRF), which is a modified system of Horizontal-Flow Roughing Filtration (HRF) by addition of a low dose of coagulant prior to filtration. To optimize the DHRF configuration, a conceptual and mathematical model for the coarse compartment has been developed in analogy with multi-plate settler. Data from simple column settling test can be used in the model to predict the filter performance. Furthermore, the model developed herein has been validated by successive experiments. The conventional column settling test has been found to be handy and useful to predict the performance of DHRF for different raw water characteristics (e.g. coagulated or uncoagulated water, different amounts of organic matter, etc.) and different initial process conditions (e.g. coagulant dose, mixing time and intensity, etc.). An optimum filter design for the coarse compartment (grain size 20 mm) has been found to be of 3m h(-1) filtration rate with filter length of 4-4.5 m.

Recovering region-specific hemodynamic response function (HRF) in noisy fMRI data is essential to characterize the temporal dynamics of functionally coherent brain regions during activation. Data-driven techniques not based on sparsity fails to recover sub-region HRFs from overlapping regions of interest (ROIs) in task-related activations. This paper exploits spatial sparsity for recovering distinct HRFs from un-delineated overlapping ROIs in fMRI data. Spatial sparsity is realized using thresholding correlation for dictionary learning. The effectiveness of the proposed procedure is illustrated on both simulated and an experimental fMRI data obtained during a visual-task.

Multiple images were recorded in DuPont HRF-150 photopolymer as transmission holograms by using angle multiplexing. Agreement with Kogelnik's two-wave diffraction theory for phase gratings, the time considerations and its effect on dynamic range, the necessity of a pre-illumination pulse, and good image quality at readout are reported.

High-risk non-muscle-invasive bladder cancer (NMIBC) that invades into the lamina propria is frequently understaged and is associated with a risk of lymph node metastasis and death.

To identify high-risk features (HRFs) for NMIBC that may identify patients with poorer prognosis who may benefit from neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC).

We performed a single-center retrospective review of patients who underwent RC for NMIBC with invasion into the lamina propria between 1995 and 2013. HRFs included hydronephrosis, abnormal examination under anesthesia, lymphovascular invasion, or variant histology.

Pathology at RC, and overall (OS) and disease-specific (DSS) survival were evaluated and analyzed by Fisher's exact test, Student t test, Cox proportional hazards regression analysis, and the Kaplan-Meier method.

We identified 336 patients with a median follow-up of 130 mo. Of these, 159 (47%) had no HRF, 140 (41.5%) had one HRF, and 37 (11%) had ≥2 HRFs. At RC, patients with ≥2 HRFs had a significantly higher rate of pathologic T stage upstaging and lymph node metastasis (p<0.05). Median OS was 139 mo for those with no HRF, 127 mo for those with one HRF, and 56 mo for those with ≥2 HRF (p=0.0057). HRFs are also associated with a decreased DSS (p=0.0009). Patients with ≥2 HRFs (11/37) who received NAC showed improved OS (21% vs 55% 5-yr OS, p=0.0353) and trended toward an improvement in DSS (25% vs 56% 5-yr OS, p=0.0716) compared with RC alone.

The presence of ≥2 HRFs in NMIBC invading the lamina propria is associated with worse pathology at RC and a significant decrease in OS and DSS. NAC appears to provide benefit for these patients. Limitations include retrospective design and limited sample size.

The presence of high-risk features in urothelial cancer with invasion into the lamina propria has a worse prognosis that may be mitigated by neoadjuvant chemotherapy.

High density diffuse optical tomography has become increasingly important to detect underlying neuronal activities. Conventional methods first estimate the time courses of the changes in the absorption coefficients for all the voxels, and then estimate the hemodynamic response function (HRF). Activation-level maps are extracted at last based on this HRF. However, the error propagation among the successive processes degrades and even misleads the final results. Besides, the computation burden is heavy. To address the above problems, a direct method is proposed in this paper to simultaneously estimate the HRF and the activation-level maps from the boundary fluxes. It is assumed that all the voxels in the same activated brain region share the same HRF but differ in the activation levels, and no prior information is imposed on the specific shape of the HRF. The dynamic simulation and phantom experiments demonstrate that the proposed method outperforms the conventional one in terms of the estimation accuracy and computation speed.

Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) maps the brain activity by measuring blood oxygenation level, which is related to brain activity via a temporal impulse response function known as the Hemodynamic Response Function (HRF). The HRF varies from subject to subject and within areas of the brain, therefore a knowledge of HRF is necessary for accurately computing voxel activations. Conversely a knowledge of active voxels is highly beneficial for estimating the HRF. This work presents a joint maximum likelihood estimation of HRF and activation based on low-rank matrix approximations operating on regions of interest (ROI). Since each ROI has limited data, a smoothing constraint on the HRF is employed via Tikhonov regularization. The method is analyzed under both white noise and colored noise. Experiments with synthetic data show that accurate estimation of the HRF is possible with this method without prior assumptions on the exact shape of the HRF. Further experiments involving real fMRI experiments with auditory stimuli are used to validate the proposed method.

Goal: We aimed to identify electroencephalographic (EEG) signal fluctuations within independent components (ICs) that correlate to spontaneous blood oxygenation level dependent (BOLD) activity in regions of the default mode network (DMN) during eyes-closed resting state. Methods: We analyzed simultaneously acquired EEG and functional magnetic resonance imaging (fMRI) eyes-closed resting state data in a convenience sample of 30 participants. IC analysis (ICA) was used to decompose the EEG time-series and common ICs were identified using data-driven IC clustering across subjects. The IC time courses were filtered into seven frequency bands, convolved with a hemeodynamic response function (HRF) and used to model spontaneous fMRI signal fluctuations across the brain. In parallel, group ICA analysis was used to decompose the fMRI signal into ICs from which the DMN was identified. Frequency and IC cluster associated hemeodynamic correlation maps obtained from the regression analysis were spatially correlated with the DMN. To investigate the reliability of our findings, the analyses were repeated with data collected from the same subjects 1 year later. Results: Our results indicate a relationship between power fluctuations in the delta, theta, beta and gamma frequency range and the DMN in different EEG ICs in our sample as shown by small to moderate spatial correlations at the first measurement (0.234 < |r| < 0.346, p < 0.0001). Furthermore, activity within an EEG component commonly identified as eye movements correlates with BOLD activity within regions of the DMN. In addition, we demonstrate that correlations between EEG ICs and the BOLD signal during rest are in part stable across time. Discussion: We show that ICA source separated EEG signals can be used to investigate electrophysiological correlates of the DMN. The relationship between the eye movement component and the DMN points to a behavioral association between DMN activity and the level of eye movement or the presence of neuronal activity in this component. Previous findings of an association between frontal midline theta activity and the DMN were replicated.

At present it is known 2 forms of hantavirus infections in humans: hemorrhagic fever with renal syndrome (HFRS) induced by viruses Hantaan, Seoul, Puumala and Dobrava/Belgrade; and hantaviral pulmonary syndrome, induced by Sin Nombre et al. A case of HRFS, induced by hantavirus Dobrava, is described. Features of this case are developed neurological manifestations against the background of renal pathology, and difficulties of clinical and laboratory diagnostics in practice.